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This is raw OCR (optical character recognition) on a scanned copy of John White's monograph, known informally as "The Mind of a Worm." This is the basis of an HTML version currently being prepared by Zeynep Altun-Gultekin and Thomas Boulin. It is being posted in this form in response to recent requests from the community. Readers are advised that the text may contain character recognition errors, and the figures are essentially unusable.
Permission to post this text was granted by the copyright holder, the Royal Society of London.
Phil. Trans. R. Soc. Lond. B 314, 1-340 (1986) [ 1 ]
Printed in Great Britain
THE STRUCTURE OF THE NERVOUS SYSTEM OF
THE NEMATODE CAENORHABDITIS ELEGANS
BY J. G. WHITE, E. SOUTHGATE, J. N. THOMSON
AND S. BRENNER, F.R.S.
Laboratory of Molecular Biology, Medical Research Council Centre, Hills Road,
Cambridge CBg 2QH, U.K.
(Received 9 August 1984-Revised 12 November 1984)
CONTENTS
PAGE
INTRODUCTION 2
MATERIALS AND METHODS 4
Electron microscopy 5
Reliability of data 6
Nomenclature 7
GENERAL DESCRIPTION OF C. ELEGANS 7
Behaviour 7
Structure 8
THE NERVOUS SYSTEM 9
Organization of nervous system and musculature 9
Sensory transduction 9
Disposition of cell bodies and ganglia 10
Disposition of process tracts 16
Musculature 10
Basal lamina 23
Neurons 25
Branching structure 25
Branch termination 27
Gap junctions 27
Chemical synapses 28
Neuromuscular junctions 29
The organization of processes within bundles 33
Circuitry 41
Triangular patterns of connectivity 47
Gap junction circuitry 47
Functional classification of neuron classes 47
Sensory receptors 48
Interneurons 49
Motoneurons 50
Vol. 314. B. II65 I [Published I2 November I986
2 J.G. WHITE AND OTHERS
Connectivity 52
Amphids 52
Other receptors in the head and their associated interneurons 53
Motoneurons in nerve ring 53
Motoneurons in ventral cord 54
Circuitry associated with neurons in the tail 56
The egg-laying circuitry 57
CONCLUSIONS 58
Process placement 58
Synaptic specificity 59
Nervous system function 60
REFERENCES 61
APPENDIX 1 63
APPENDIX 2 339
APPENDIX 3 340
The structure and connectivity of the nervous system of the nematode Caenorhabditis
elegans has been deduced from reconstructions of electron micrographs of serial
sections. The hermaphrodite nervous system has a total complement of 302 neurons,
which are arranged in an essentially invariant structure. Neurons with similar
morphologies and connectivities have been grouped together into classes; there are
118 such classes. Neurons have simple morphologies with few, if any, branches.
Processes from neurons run in defined positions within bundles of parallel processes,
synaptic connections being made en passant. Process bundles are arranged longitudi-
nally and circumferentially and are Often adjacent to ridges of hypodermis. Neurons
are generally highly locally connected, making synaptic connections with many of
their neighbours. Muscle cells have arms that run out to process bundles containing
motoneuron axons. Here they receive their synaptic input in defined regions along
the surface of the bundles, where motoneuron axons reside. Most of the morpho-
logically identifiable synaptic connections in a typical animal are described. These
consist of about 5000 chemical synapses, 2000 neuromuscular junctions and 600 gap
junctions.
INTRODUCTION
The functional properties of a nervous system are largely determined by the characteristics of
its component neurons and the pattern of synaptic connections between them. Although great
progress has been made this century in understanding the manner in which information is
coded within a neuron and the process of information transmission between neurons via
synapses, little is currently known about the detailed connectivity of networks of neurons. The
reason for this is simply that a nervous system is an enormously complex organ. In the
vertebrate cerebellum alone, it has been estimated that there are more than 10lø neurons
(Braitenberg & Atwood 1958) each making many thousands of synaptic contacts.
We have undertaken a complete reconstruction of a nervous system from electron micrographs
of serial sections. We have been able to do this by using a very simple, small nervous system,
that of the soil nematode Caenorhabditis elegans. The simplicity and consistency of structure of
the nematode's nervous system attracted the attention of several neuroanatomists at the turn
THE MIND OF A WORM 3
of the century. Richard Goldschmidt was perhaps the most notable of these; he attempted to
reconstruct the nervous system of the large parasitic nematode Ascaris lumbricoides from serially
sectioned material. Goldschmidt and his contemporaries produced detailed and accurate
descriptions of the sensilla, the ganglia and the process tracts (Chitwood & Chitwood 1974),
but the limited resolution of the light microscope prevented them from unambiguously
resolving individual processes within bundles. Goldschmidt was convinced that neuron
processes anastomosed extensively and that nervous tissue was therefore a syncytial network.
He presented a set of intriguing diagrams representing the layout of processes in the Ascaris
nervous system in support of his view of the structure of nervous tissue, a view that he
vigorously defended (Goldschmidt 1908, 1909). The alternative viewpoint considered that
neurons are mononucleate branched structures and that their processes do not anastomose. It
is now clear that this alternative viewpoint, as espoused by his contemporary critics, such as
Cajal (1972), was correct. More recent anatomical studies with the electron microscope have
finally laid to rest the reticularists' view of the nervous system. We have therefore not tried
to interpret Goldschmidt's connectivity diagrams, although we have retained some of the
names, given to the sensilla and ganglia, that were used by him and his contemporaries.
In recent years, C. elegans has become an object of intense developmental and genetical study.
The highly reproducible sequence of cell divisions that takes place during the development of
this organism has allowed the complete cell lineage to be determined from the fertilized zygote
to the mature adult (Sulston 1983; Sulston et al. 1983). Each differentiated cell type that is
produced at the terminal twigs on the lineage tree is now known. Laser ablation studies have
given some insight into the degree of cell autonomy that is involved in determining the pattern
of cell divisions and differentiations that occur. Generally it seems that, in C. elegans, cells
behave fairly autonomously during development, although there are several well-defined
instances where regulative cell-cell interactions have been demonstrated (Sulston & White
1980; Kimble 1981 ).
C. elegans was originally selected as an organism worthy of extensive developmental studies,
partly because it is readily amenable to genetic analysis. Many mutants have been isolated and
mapped (Brenner 1974). The mutants that have been isolated exhibit a wide variety of
phenotypes' some are morphological, some affect various aspects of development and many
exhibit aberrant behaviour. Some of the behavioural mutants have been shown to have defects
in muscles (Waterston et al. 1980), but many probably have alterations in the nervous
system (Lewis & Hodgkin 1977; Chalfie & Sulston 1981; Hedgecock et al. 1984). It is hoped
that a detailed knowledge of the structure of the wild-type nervous system of C. elegans will
facilitate the interpretation of the changes that occur in such mutant nervous systems. This may
in turn shed some light on the genetic control of the developmental processes that ultimately
give rise to the specifically interconnected group of neurons that make upa nervous system.
The reconstructions that are presented in this paper describe the connectivity of all the
neurons in the nervous system of the C. elegans hermaphrodite except those in the pharynx,
which have been described by Albertson & Thomson (1976). The detailed morphologies of
the sensilla in the head have been described by Ward et al. (I975), Ware et al. (1975) and
Wright (1980); the structure of the ventral cord has been described by White et al. (1976) and
an independent reconstruction of the tail ganglia has been described by Hall (1977). Together
these papers give a fairly complete description of the connectivity, topography and ultrastructure
of the nervous system in the hermaphrodite. The C. elegans male has a more extensive nervous
I-2
4 J.G. WHITE AND OTHERS
system than that of the hermaphrodite; most of the 'extra' nervous tissue is situated in the
tail. A partial reconstruction of the nervous system in the male tail has been described by
Sulston et al. (1980).
The structure of the ventral cord of Ascaris has been deduced from reconstructions of light
micrographs of serial sections (Stretton et al. 1978). In spite of the enormous difference in size
between these two nematodes (10 cm as against 1 mm for C. elegans), the motoneurons in the
ventral cord turn out to be remarkably similar, and it has been possible to identify equivalent'
motoneuron classes in the two animals. The large size of Ascaris enables electrophysiological
techniques to be used in the study of its nervous system. Such studies have identified inhibitory
and excitatory classes of motoneuron and have shown that acetylcholine is the neurotransmitter
used by the excitatory motoneurons (Johnson & Stretton 1980). The small size of C. elegans
precludes such electrophysiological studies but, by analogy, these results may be related to
the equivalent neurons in C. elegans and so provide clues as to their functional properties.
Although reconstructions of nervous tissue from electron micrographs can in principle
identify all focal synaptic contacts, it is unlikely that the pattern of connectivity obtained would
exactly represent the functional synaptic connections between neurons. There is evidence that
synaptic transmission mediated by some peptide transmitters acts over a considerable range
(Jan et al. 1983), suggesting that these types of synapses may not be localized at discrete focal
contacts and therefore would not be seen in electron micrographs. There are other routes by
which transmission of information could occur between neurons which are not apparent from
reconstructions. Neurohumoral transmission is probably used for transmission over long
distances and where many targets may be involved; a good candidate for a neurosecretory
neuron has been found in the pharynx (Albertson & Thomson 1976). Short-range transmission
may occur by means of electrical leakage currents or by capacitive coupling between processes
that run alongside each other for long distances. However, in spite of these limitations,
high-resolution reconstructions provide a wealth of information on the synaptic contacts
between neurons. Thus, of all the currently available techniques, such reconstructions probably
provide the most comprehensive picture of the synaptic circuits of a nervous system such as
that of C. elegans.
Because of the large amount of information that is involved in presenting the connectivity
data, we have tried to organize its presentation in such a way as to facilitate quick access. The
structure of a 'canonical' nervous system is presented, which is in fact a mosaic of several
nervous systems. A general descriptions first given of the structure of C. elegans and some of
the salient features of the nervous system. This is followed by a detailed description of each
of the neuron classes arranged in alphabetical order in Appendix 1. These descriptions are fairly
self-contained and include morphological as well as synaptic data. There are many references
in the first section to illustrations in Appendix 1. These appear as the class name followed by
a letter, e.g. ASE-a. The lower case letter indicates the diagram referred to in the description
of the neuron class ASE.
MATERIALS AND METHODS
The reconstructed nervous systems described in this study were all derived from the
nematode Caenorhabditis elegans (var. Bristol); these were cultured on lawns of E. coli grown on
agar Petri plates (Brenner 1974).
THE MIND OF A WORM 5
Electron microscopy
Worms were rinsed off Petri plates and fixed in 1% osmium tetroxide in 0.1 M sodium
phosphate, pH 7.4 for one hour at 20 øC. Pre-fixing in glutaraldehyde was not done in this work
because, although this method gives better preservation of fine structure, we found that osmium
alone gave better contrast to cell membranes, and this facilitated the resolution of process
outlines in regions of dense neuropile.
After fixation, the worms were spread on a thin layer of 1% agar and cut in half. The cut
worms were covered with a drop of molten 1% agar, and blocks of agar containing a single
half worm were cut out. These were dehydrated through a graded series of alcohols to propylene
oxide, then to propylene oxide plus Araldite (CY 212 resin, CIBA Ltd.) and then into Araldite
at room temperature overnight. The following day they were transferred to fresh Araldite and
polymerized in gelatin capsules overnight at 60 øC.
An LKB ultratome III was used with a diamond knife to cut transverse serial sections of
approximately 50 nm thickness. Ribbons of sections were generally picked up on Formvar
coated 75-mesh copper grids. The sections in the region of the head, where most of the nervous
system is situated, were picked up on slot grids, as it was found to be necessary to have every
section in this region for successful reconstructions. Grids were stained with a 5 % aqueous
solution of uranyl acetate for 10 min at 60 øC and then with lead citrate for 5 min at room
temperature according to the procedure of Reynolds (1963). Sections were photographed on
cut film with an AEI 6B or an AEI 802 electron microscope. Most reconstructions were done
directly from prints of micrographs of nervous tissue. In the region of the nerve ring, four-way
montages were necessary; in other regions, single prints were sufficient. Every section was
photographed in the region of the nerve ring and other areas of dense neuropile: photographs
of every third section usually sufficed for following process bundles. Some use was made of a
computer-aided reconstruction system described by White (1974) and Stevens & White (1979),
but most of the reconstructions were done by hand from a total of about 8000 prints.
Small groups of processes were given arbitrary labels, which were written onto the prints
with Rotting drafting pens. These labels were carried through all the pictures in which the
associated processes were present, and this procedure was repeated until all process profiles
were labelled. Processes could then be joined to other processes where branches had occurred,
or ultimately be assigned to particular neurons if their cell bodies were within the scope of the
reconstruction. When all the labelling was completed, each process was individually followed
through every section in which it appeared, and a list was compiled of all the synaptic contacts
that it made. In this way all synaptic contacts were recorded twice, once for each member of
an interacting pair of processes. This provided a useful check on synapse scoring as any synaptic
contact that was only scored once was reappraised.
The reconstructions were done piecemeal with data from five overlapping series; these were
designated N2T, N2U, JSH, N2Y and JSE (figure A 1, Appendix 1). The structure was found
to be sufficiently invariant for equivalent processes and cell bodies to be identified in the region
of overlap of two series. The N2T series was the first extended series to be cut in the head;
the reconstructions of the head sensilla described by Ward et al. (1975) were based on this series.
Although this series extended through the nerve ring and into the ventral cord, mesh grids were
used and it was found that the inevitable occasional section loss, through obscuration by grid
bars, allowed only a limited reconstruction to be done of these regions. The NgU series was
6 J.G. WHITE AND OTHERS
from an old hermaphrodite that gave good quality pictures. It was sectioned on slot grids
through the nerve ring and anterior ventral cord and a complete reconstruction of this region
was obtained. This series also covered more than half the body length of the animal and
enabled the anterior ventral and dorsal cords to be reconstructed. The JSH animal was a fourth
stage (L4) larva, which was sectioned on slot grids. A complete reconstruction of the nervous
system in the nerve ring and anterior ventral cord was obtained from this animal. This allowed
the structure deduced from the N2U series to be validated in these regions, which are the most
difficult to reconstruct because they contain dense neuropile with many processes that run close
to the plane of sectioning. Few significant differences in structure that could be age-related were
seen between the N2U and JSH series. The tail ganglia and some of the posterior ventral and
dorsal cord were covered in the JSE reconstruction. The region between the anterior extremity
of the JSE series and the posterior extremity of the N2U series has not been reconstructed in
a hermaphrodite. A long series that overlapped at both ends, designated N2Y, was obtained
from a male animal (Sulston et al. 1980, in which it was referred to as series 4). The
motoneurons of the ventral cord and the cells from the posterior lateral ganglion were
reconstructed from this animal. The motoneurons (with the exception of the sex-specific VCn
class) exhibited essentially the same synaptic behaviour as their anterior counterparts in the
hermaphrodite. As there was also no reason to expect any sex-related differences in the cells
of the posterior lateral ganglia, these data were incorporated to enable a complete reconstruction
of the whole nervous system to be obtained. The structure that is described is a composite that
has been derived from all these series except JSH.
Reliability of data
The biggest problem that was encountered in the course of the reconstruction work was the
location of errors. Errors were generally made in one of three ways. (1) The most prevalent
was human error, which would occur when following long featureless process bundles and
which typically resulted in switches in process labels. (2) Many processes run close to the plane
of sectioning in the vicinity of the nerve ring, with the result that the membranes of these
processes would often be cut obliquely and give indistinct images. This made process
identification very difficult in such situations, leading to the second most prevalent source of
errors. (3) Similar errors of process identification also occurred in regions of poor image quality
caused by dirt on sections or loss of sections on grid bars although, surprisingly, this was the
least prevalent source of errors.
Errors generally manifested themselves by the appearance of an improbable structure, such
as a process that was joined to more than one cell body or conversely not joined to any at all.
Much of the nervous system was found to be bilaterally symmetrical; some of the sensory
receptors in the head have higher levels of symmetry. Any deviations that were seen from
expected symmetries were considered suspect. Errors were located either by exhaustive
searching of every section that contained the process that was in question, or by looking at the
reconstructions for discontinuities in synaptic behaviour, and then closely checking the regions
of the process where the discontinuities occurred. In this way a complete, self-consistent
structure was built up. The structures of the major regions of neuropile have been validated
by separate reconstructions; the JSH series in the case of the nerve ring and the Ngs series
in the case of the ventral cord (White et al. 1976). Hall has undertaken an independent
reconstruction of the tail ganglia; the structure that he describes is essentially the same as the
structure that we describe here (Hall 1977).
THE MIND OF A WORM 7
We are reasonably confident that the structure that we present is substantially correct and
gives a reasonable picture of the organization of the nervous system in a typical C. elegans
hermaphrodite. It is likely that in the elaboration of a structure of this complexity that a few
small errors might have crept in, but we feel that these may be quite limited because of the
amount of cross-checking that was done. A few minor ambiguities still exist, however, which
would require a considerable effort to clear up. These are described in Appendix 2.
Nomenclature
We have adopted a uniform system of nomenclature for naming the neurons and associated
cells of C. elegans: Unfortunately it was not practicable to make such a system compatible with
the various nomenclatures that have been used up till now. Appendix 3 lists the equivalences
between these systems and the one used in this study.
Neurons are given arbitrary names consisting of three upper case letters. The last letter can
alternatively be a number of up to two digits. Additional symmetry descriptors are added to
the name in the cases of groups of cells that are in the same class and related to each other
by simple geometric symmetries. These descriptors are D or V (dorsal or ventral) and L or
R (left or right). A group of cells with six-fold symmetry, such as IL1, has as its members:
IL1DL, IL1DR, IL1L, IL1R, IL1VL and IL1VR. The members of the classes of motoneuron
in the ventral cord do not have these symmetrical relations with each other. In these cases,
the third digit of the class name is a numeral, which represents the anterior or posterior location
of the neuron relative to its fellow class members; for example, VA3 is the third VA
motoneuron. The use of the three-letter name without descriptors implies all members of the
class if there is more than one. For the motoneurons, a lower case n is used in the third digit
position to represent the generic name for all class members (for example, VAn).
A slight modification of this system is used to describe the associated cells of sensilla, i.e. the
sheath and socket cells. A sheath cell is designated by 'sh' and a socket cell 'sa'. Thus in the
case of the right sub-dorsal cephalic sensillum, the neuron is referred to as CEPDR, the sheath
cell as CEPshDR and the socket cell as CEPsoDR.
GENERAL DESCRIPTION OF C. ELEGANS
C. elegans is a small, free-living, soil nematode worm. It has a generation time of about 3.5 d
and grows to a length of 1.3 mm and a diameter of 80 [tm if there is a plentiful supply of food.
It is a self-fertilizing hermaphrodite, one animal generally giving rise to about 300 offspring.
Occasionally, at a frequency of about 1 in 10a, a male is produced, which is capable of mating
with the hermaphrodites. C. elegans can easily be cultured in the laboratory on bacterial lawns
grown on an agar substrate. Mutations may be readily produced by a variety of mutagens and
will segregate out as homozygous clones without having to set up back-crosses. These
characteristics make the animal very amenable to genetic analyses, and many behavioural and
morphological mutants have been mapped (Brenner x974; Swanson et al. 1984).
Behaviour
The animals pass through four larval stages before reaching adulthood' L1, L2, L3 and L4.
Each stage is terminated by a moult. If food is scarce, animals can go through an alternative
developmental sequence in which a resistant 'dauer' larval form is produced at the L2 to L3
moult. Dauers can survive extreme conditions (desiccation and lack of food) for long periods
8 J.G. WHITE AND OTHERS
until conditions improve and food becomes available, at which time they will moult and
become normal adults (Cassada & Russell 1975; Riddle et al. 1981 ). Several structural changes
occur on entering the dauer stage, including alterations to the endings of some sensory receptors
(Albert & Riddle 1983).
C. elegans normally inhabits the interstices between damp soil particles or in rotting
vegetation. It lives in a film of water and is held to solid surfaces by surface tension. Locomotion
is achieved by dorso-ventral flexures of the body, which give rise to sinusoidal wave
propagation along the length of the body. This can either be in the anterior-to-posterior
direction, giving rise to forward motion, or in the posterior-to-anterior direction, giving
backward motion. The head has an extra degree of freedom, in that it can make lateral as well
as dorso-ventral movements. The dorso-ventral flexures (with the consequential sinusoidal
posture of the body), combined with the surface tension forces, constrain the animals to lie on
their sides. The L1, dauer and adult stages have longitudinal lateral ridges of cuticle, the alae,
which may act to increase lateral friction and minimize sideslip. The thickness of the water
film is quite critical; too thin or no water film results in the animals' becoming desiccated and
dying, whereas if the film is greater than their diameter they are not held down to the surface
and are unable to make any progress. C. elegans can move well on an agar surface even though
this must be quite different from its normal habitat. If there is no food available locally it will
move forward for quite long periods with occasional short intermissions of reversing. When it
locates food it starts eating and stops moving, except for short foraging excursions forwards and
backwards. Eggs tend to be laid only when the hermaphrodites have a plentiful food supply.
C. elegans responds in a regulated manner to a number of sensory stimuli: it will chemotax
up a gradient of chemical attractant or down a gradient of repellant (Ward 1973; Dusenbery
1974); it will avoid regions of high osmolarity (Culotti & Russell 1978); it will actively
maintain itself at an optimum temperature in a temperature gradient (Hedgecock & Russell
1975) and it will respond to light touch by moving away from the point of stimulation (Chalfie
& Sulston 1981). In addition to these responses, the worm presumably uses its mechanosensory
system to navigate through the interstices between soil particles in its natural habitat.
Mating-specific behaviour is exhibited only by the male (Hodgkin 1983), which has additional
neural circuitry in the tail for controlling copulation (Sulston et al. 1980).
Structure
The animal is ensheathed in a tough impermeable elastic cuticle, which is laid down by a
system of underlying hypodermal cells. The body cavity (the pseudocoelome) is maintained
at a high hydrostatic pressure relative to the outside; it is this pressure, acting on the elastic
cuticle, which gives the animal its rigidity (the so-called hydrostatic skeleton (Crofton 1966)).
There are four longitudinal ridges running down the inside of the body cavity: two medial
and two lateral. These ridges consist of a ridge of hypodermis adjacent to a bundle of nerve
processes, the whole structure being bounded by a basal lamina. Body movements are mediated
by four strips of muscle cells running in four quadrants between these longitudinal ridges.
Muscle cells have no obvious attachment points at either end and probably have attachments
to the hypodermis distributed along their length. They act to deform the cuticle elastically
against the stress produced by the turgor pressure.
Food is pumped into the animal and processed by a prominent pharynx. This is a virtually
self-contained organ with its own musculature, epithelium and nervous system, and has been
described in detail by Albertson & Thomson (1976). The pharynx probably functions as a
THE MIND OF A WORM 9
largely autonomous unit, although there are two interneurons that originate in the central
nervous system and enter it. These interneurons (RIP) are exclusively postsynaptic outside the
pharnyx and so probably mediate the overall control of pharyngeal pumping from the central
nervous system. The pharynx is used for ingesting food (usually bacteria), concentrating it by
filtration and then grinding it, and probably also for secreting digestive enzymes from its gland
cells (Albertson & Thomson 1976). The processed food is pumped into the intestine, which
has a lumen lined with microvilli. The intestine is connected with the anus; defecation is
controlled by three sets of specialized muscles (figure 12).
There is an excretory system, which consists of a single excretory canal cell arranged in an
' [4' configuration (Bird 1971 ). The two arms of the Iq run longitudinally down the lateral lines.
These are joined by a cross bridge, which is connected to the excretory duct on the ventral
side; this opens to the outside of the animal via the excretory pore situated on the ventral
mid-line. Two ventrally situated 'gland' cells have anteriorly directed processes, which fuse
and connect to the lumen of the excretory canal near the pore (Nelson et al. 1983). These
processes continue running anteriorly on the ventral surface of the ventral nerve cord (figure
16) until the nerve ring is reached, where they terminate. The function of these glands is not
yet known.
The adult hermaphrodite reproductive system consists of symmetrical pairs of uteri,
oviducts, spermathecae and ovaries, which are joined at the uteri and connect to a vulva. This
is situated on the ventral mid-line about halfway down the body (Hirsh et al. x976). During
development, sperm are produced before oocytes and are stored for subsequent use. Egg-laying
is mediated by a set of sixteen muscle cells, eight of which act to squeeze the contents of the
uteri and eight to open the vulval orifice (figure 11).
The male gonad joins the rectum via the vas deferens to form a cloaca in the tail (Sulston
et al. 1980). The cloaca is surrounded by a large, fan-like, copulatory bursa, which is richly
endowed with sensory endings. These endings are derived from male-specific neurons, which
are generated post-embryonically along with other neurons in the male. The male also has
extra ventral body muscles and muscles that control the copulatory spicules (Sulston et al.
1980).
THE NERVOUS SYSTEM
Organization of the nervous system and musculature
There are 302 neurons in the nervous system of C,i elegans; this number is invariant between
animals. Each neuron has a unique combination of properties, such as morphology, connectivity
and position, so that every neuron may be given a unique label. Groups of neurons that differ
from each other only in position have been assigned to classes. There are 118 classes that have
been made using these criteria, the class sizes ranging from 1 to 13. Thus C. elegans has a rich
variety of neuron types in spite of having only a small total complement of neurons. This is
in marked contrast to structures such as the mammalian cerebellum, which contains more than
10lø neurons (Braitenberg & Atwood 1958) and yet has only five classes of component neuron
(Eccles et al. 1967).
Sensory transduction
The bulk of the nervous system of C. elegans is situated in the head, which is richly endowed
with sensory receptors. These are arranged in groups of sense organs, known as sensilla. The
arrangement and structure of sensilla have been described in detail (Ward et al. 1975; Ware
10 J.G. WHITE AND OTHERS
et al. 1975; Wright 1980). Each sensillum contains one or a number of ciliated nerve endings
and two non-neuronal cells' a sheath cell and a socket cell. A socket cell is effectively an
interfacial hypodermal cell acting to join the sensillum to the hypodermis. A sheath cell is a
glial-like cell that envelops the endings of neurons. Its inner surface, adjacent to the neural
dendrite, is extensively invaginated and large number of secretory-like vesicles are often present
in the cytoplasm. The sheath cells of the cephalic sensilla have, in addition, fiat sheet-like
processes that partly envelop the neuropile of the nerve ring and the anterior extremity of the
ventral cord (figure 16). The function of sheath cells is not known, but they probably act to
establish a defined extracellular milieu for the receptor endings.
Two large sensilla, the amphids, are located laterally and have internal channels, formed
by the sheath and socket cells, which open through the cuticle to the outside. Eight neurons
have their ciliated endings in this channel; a further four are associated with the sheath cell.
There are two analogous structures, the phasmids, in the tail, but they are simpler in that they
only have two neurons ending in the channel. The amphids and phasmids are generally
considered to be the main chemoreceptive organs in the animal, because their structure permits
a group of nerve endings to be exposed to the external environment of the animal.
The other sensilla in the head are arranged into two concentric rings around the mouth
(figure 1). There is an inner ring of six, the inner labial sensilla, each of which has two
associated neurones (II1 & IL2). The dendrites of IL2 penetrate the cuticle to the outside of
the animal and so they could be chemoreceptors. The other ending (IL1) lies embedded in
the cuticle. There is an outer ring of four sensilla, the quadrant outer labials (OLQ.), and these
are paired with another set of four, the cephalic sensilla (CEP). Two additional lateral outer
labial sensilla (OLL) are situated next to the amphid channel openings. The only other sensilla
in the hermaphrodite are two pairs of lateral sensilla, the deirids, situated laterally in the
anterior body (ADE) and the posterior body (PDE). These sensilla have similar morphologies
to the cephalic sensilla in the head (Ward et al. 1975).
In addition to the neurons of the sensilla there are other classes of neuron, which, on the
basis of their connectivity and morphology, also probably serve a sensory transduction
function. The best characterized neurons of this type are the touch receptors ALM, PLM,
AVM and PVM. These have specialized, microtubule-filled processes, which run in close
apposition to the hypodermis (Chalfie & Sulston 1981).
Disposition of cell bodies and ganglia
Several ganglia have been described and named in the nervous systems of other nematodes
(Chitwood & Chitwood 1974). We have retained these names, where appropriate, for the
ganglia in C. elegans. In several regions, cells are grouped together into well-defined ganglia
by the arrangement of the basal lamina in the pseudocoelome. This sometimes results in
adjacent cells' being partitioned into different ganglia. The lateral and ventral ganglia are not
obviously separated in figure 2, for example, but in fact the cells of the ventral ganglion are
a well-defined group (figure 3), being separated from those of the adjacent lateral ganglia by
two basal laminae (figure 13). The arrangement of the basal lamina around the pseudocoelome
will be discussed later; we will now describe the disposition of the various ganglia.
Most of the neurons of C. elegans have their cell bodies situated in the head around the
pharynx (figure 2). The pharynx is composed of two prominent bulbs joined by an isthmus.
An extensive region of neuropile, the circumpharyngeal nerve ring, encircles the centre region
THE MIND OF A WORM 11
~ O ,,AFDR
* d'
f/ øø O Ooo
0~ o 0 i :"' Oo o
' 0 :~':-,.~ 0 'FL PL / .....
.... !i .:':::-% ....
A S K L"'"-- -- O ' ..c
......... :0~ '0
^. ^:,L V .... 0› .....
,BAGL / ~ OLLR
OLQVR
)RYVR
FIGURE 1. Sensory receptors in the head, as seen in an idealized section near the tip of the head. This region is richly
endowed with sensory receptors, which are organized in a precise, complex arrangement. Most of the receptors
are components of sensilla, and have associated sheath and socket cells. The amphid sensilla are situated in
the lateral labia and have channels that are open to the outside with ADL, ADF, ASG, ASH, ASE, ASI, AS,]
and ASK entering them. AWA, AWB, AWC and AFD are associated with the amphid sheath cells. There
is a single inner labial sensillum in each labium, containing IL1 and IL2 receptor neurons. These sensilla also
have channels to the outside, through which the processes of IL2 project. The two dorsal and the two ventral
labia each have a single cephalic sensillum with a CEP receptor, and a single outer labial sensillum with an
OLO receptor. The lateral labia also each have an outer labial sensillum but with an OLL receptor. FLP and
BAG are ciliated receptors that are free inside the head and are not part of a sensillum. URX and URY are
not ciliated but have specialized flattened endings, which insinuate themselves around the inner and outer labial
sensilla.
of the isthmus and has cell bodies clustered adjacent to it both anteriorly and posteriorly. There
are no obvious subgroupings of the neuron cell bodies anterior to the ring and so these have
been lumped together and referred to as the anterior ganglion. The anterior ganglion is mainly
made up of the cell bodies of neurons, sheath cells and socket cells from the sensilla that are
located in the six labia of the head (figure 1). The relative positions of cell bodies within ganglia
are fairly well conserved between animals of the same developmental stage and genotype.
There is a certain amount of 'slop', however; the extent of this can be seen by comparing the
.left and right sides illustrated in figure 2. The most extreme cases of variability in this region
arise because the anterior bulb of the pharynx fits fairly tightly in the body cavity and excludes
cell bodies from its region of maximum diameter. This leads to some uncertainty in the position
of some cell bodies with respect to the bulb; for example, in the NgU reconstruction, OLQsoDL
lies anterior to the bulb, whereas its symmetrical partner, OLOsoDR, lies posterior to the bulb
(figure 2). In live animals, cells can sometimes be seen to flip from one side of the anterior bulb
to the other as the pharynx moves.
12 J.G. WHITE AND OTHERS
THE MIND OF A WORM 13
Posterior to the nerve ring, the basal laminae split the cell bodies adjacent to the ring into
four groups (figure 13): a small dorsal ganglion, two lateral ganglia, and a ventral ganglion
(figure 3). All receptor neurons of the amphid sensilla have their cell bodies in the lateral
ganglia, which also contain cell bodies of motoneurons and interneurons. The dorsal ganglion
contains interneurons together with the neurons of the two dorsal cephalic sensilla. The ventral
ganglion contains interneurons and motoneurons. The cell bodies of the ventral ganglion are
separated into two groups (figure 3) by a mechanical intrusion, as are the cells of the anterior
ganglion. In this case it is the excretory duct and canal that displaces the cells.
SIBVL --"'-""
;IAVL EXCRE~TOR y
AVF~SA*VL
FIGURE 3. View of the ventral gang]ion. The ceils of the ventral ganglion are bounded by a basal lamina, which
separates them from cells of the lateral ganglia even though they are adjacent (figure 2). The posterior region
of the ganglion is interrupted by the presence of the excretory duct and excretory canal cells, which exclude
the cell bodies of neurons from this region. VB2, AVFR and SABVL are part of the retro-vesicular ganglion
and are separated from the cells of the ventral ganglion by a basal lamina. All the cells of the ventral ganglion
project into the nerve ring, and several of the cell classes present also have members in the lateral ganglia.
The posterior extremities of the ventral ganglion overlap the anterior of the retrovesicular
ganglion, which is situated on the ventral mid-line posterior to the excretory pore (figure 2);
however, the two groups of cells are distinct, being separated by basal laminae. A single row
of cell bodies runs down the ventral mid-line (figure 4) from the retro-vesicular ganglion to the
tail, where it ends in another ganglion, the pre-anal ganglion. There are three extra ganglia
in the tail: two laterally symmetric lumbar ganglia and a single, small dorso-rectal ganglion
(figure 5). There is a pair of small lateral ganglia in the posterior body, the posterior lateral
ganglia, and there are some isolated cells along the body laterally (figure 4).
The anterior ganglion, the ventral ganglion and the dorso-rectal ganglion are completely
DESCRIPTION OF FIGURE 2
FIGURE 2. The locations of the cell bodies of all the neurons and their associated cells in the head is shown in left-hand
(a) and right-hand (b) views. Cells marked with an asterisk are on or near the centre line and are shown in
both views. These diagrams were derived from reconstructions of electron micrographs of one animal and,
because of the difficulty of accurately measuring section thickness, there may be some longitudinal distortion.
This is not excessive, however, as the overall longitudinal scale was normalized to views taken from the light
microscope. The anterior bulb of the pharynx fits tightly in the body hypodermis and excludes cell bodies in
the region of its maximum diameter. Cell bodies that are in this region are sometimes indeterminate as to which
side of the bulb they reside, as in OLQsoDL/R. The neuropile of the nerve ring also excludes cell bodies and
gives rise to the bare region around the isthmus of the pharynx.
14 J.G. WHITE AND OTHERS
[
VA2
VB3
AS2 ~ DB3
VD3 -- DA2
VA3
VCl
AS3 DD2
......... I ::iiii ....
LATERAL ~ DA3
GANGLION VA4
VB5
Ye2
DB4
AS4
VD5
VA5
DA4
VB6
DD3
Vt3
AS5 --
VD6
VENTRAL
CORD
MOTONEURON ES
VA6
CANR ~ VB7
DB5
AS6
VD7
VC4
DA5
VC5 --
VA7 --
VB8
AS7 --
ALMR -- DD4
VD8 --
VA8 --
VB9 --
VC6
AS8 ~ ~ DB6
PVDL / I GANGLIoNPOSTERIOR
LATERAL VD9
PVM jO DA6
VA9
AS9
DD5
0
__ ~) ú DB7
__ DA7
PRE--ANAL I
r r r
FIGURE. 4. For description see opposite.
THE MIND OF A WORM 15
DVB DVA DVC ALNL PHshL PHsolL
2L
~ PVQL PQR PLNL PLML
VA11 PDA I LUMBAR GANGLION I
PVPR PVPL PDB
I
PRE--ANAL GANGLION
DORSO- RECTAL GANGLION
PVWR PVR
PVNR ~PHshR \ ALNR
r
PHCR LUAR PLNR PVQR
bounded; that is, they have clear structurally defined limits to their extents. The others are
'open' in that there are no specific boundaries at one end. The retrovesicular ganglion is open
and continuous with the region containing the motoneurons of the ventral cord, which in turn
is open and continuous with the pre-anal ganglion. Similarly, the lateral ganglia are open and
continuous with the isolated cells on the lateral lines, the posterior lateral ganglia and the
DESCRIPTION OF FIGURE 4:
FIGURE 4:. The locations of the cell bodies of all the neurons and their associated cells in the body are shown on
the left-hand side (a), the right-hand side (b) and the middle (c). These diagrams were derived from light
microscope observations (Sulston & Horvitz 1977). The asymmetries in the positions of SDQL/R, AVM and
PVM are a consequence of the different migration patterns of the initially bilaterally symmetric precursor cells
QL and QR. The ventral cord motoneurons shown in (c) can be separated into those that are present at
hatching, shown by the labels on the right, and those that develop postembryonically, shown by the labels on
the left. The anterior-posterior sequence of cell types in these two groups is always the same, but there is some
slight variation in the way the two groups intercalate, giving some variation in the combined adult sequence.
113 J.G. WHITE AND OTHERS
lumbar ganglia. Thus the body has three main compartments where neuron cell bodies are
located, two lateral and one ventral.
There seem to be no functional correlates to the groupings of cells into particular ganglia.
Often cells are more analogous, in structure and connectivity, to cells in other ganglia than
to cells in the same ganglia. Ganglia simply seem to be local groupings of cell bodies brought
about by extraneous mechanical factors.
Disposition of process tracts
The nervous system of C. elegans is made up of a set of interconnected parallel process bundles.
These run either longitudinally or circumferentially, adjacent to hypodermal tissue (figures 6
and 7). The two sub-dorsal and the two sub-ventral labia at the tip of the head each have a
single process bundle associated with them. This is made up of processes from the sensilla in
the labium, together with other processes that terminate near the sensilla but have no
differentiated endings. The lateral labia have similar process bundles but, in addition, each
has a larger process bundle made up of processes of the neurons of the amphid sensilla. Most
of the processes in the six non-amphidial bundles have associated cell bodies, which are situated
in front of the nerve ring in the anterior ganglion. Individual processes peel away from the
bundle to join their (bipolar) cell bodies. A second, posteriorly directed process emanates from
the cell body and rejoins the process bundle, running in the same region of the bundle as its
anteriorly directed counterpart. The six labial process bundles run posteriorly past the outside
of the nerve ring and then turn to enter the nerve ring near its posterior face (figure 6). The
processes in the amphid bundle bypass the ring completely and run to their (bipolar) cell
bodies, situated in the lateral ganglia. Axonal processes from these cell bodies, along with
processes from monopolar cell bodies of interneurons and motoneurons, enter the nerve ring
via two main routes. Cells in the ventral region of the lateral ganglia have processes that join
the amphidial commissures; these run circumferentially round the animal, between muscle and
hypodermis, to the ventral mid-line, where they turn and enter the nerve ring. Cells in the
dorsal regions of the lateral ganglia do not take this somewhat circuitous route but enter the
nerve ring directly sub-dorsally.
The circumpharyngeal nerve ring is the most extensive region of neuropile in the animal
and consists of a large toroidal bundle of processes, most of which have entered the ring from
the process tracts described above. The processes in the nerve ring are derived from the sensory
receptors in the head, interneurons, and motoneurons that innervate head muscles via
neuromuscular junctions (NMJs) situated on the inside surface of the ring. The cell bodies of
both the interneurons and the motoneurons are situated in the lateral and ventral ganglia.
A large process bundle, the ventral nerve cord (figures 6-8 and 18), runs along the ventral
mid-line extending from the ventral region of the nerve ring. The cord enlarges in this region
because additional processes are joining it from the amphid and deirid commissures (figure 6).
The excretory duct splits the process bundle of the cord into two nearly equal parts as it opens
to the outside of the posterior end of the ventral ganglion. A single line of motoneuron cell
bodies is situated along the ventral mid-line (figure 4), closely apposed to the process bundle
(figure 18). These motoneurons innervate body muscles; some innervate ventral muscles and
others innervate dorsal muscles. This latter class send processes round to the dorsal mid-line
via commissures (figure 7). These then turn either anteriorly or posteriorly and together make
up another process bundle on the dorsal mid-line, the dorsal cord (figures 7 and 19). The dorsal
THE MIND OF A WORM 17
m 4:
,, << ~ .~›~ -~ .~
U
.=~o~=~~ø
O ~ ,-. ,-,.w ~ _ ~ ~ ~ ~ ~
= ~.~ ~ ~n o, ~ ~ ~ ú
, ~ ~: o,~-~ ~ ~,-~', o~
›J ,.D ~ ~ ú ,-+-~
›.) ~%7~,~ ~ ~ ~ ~ ~ ~
I
~ ~ ~ ~ .~J ~ c.,~
"~: ~ ~ ~ ~~ ~-7~
= ,~, ~:~.;'~, .. ~ ~. --
ú ,-~ ---, ,-.q ~ "'~ ,-- u.~ ~-~ ,. -- e-,
~'~ ~"9 ~'~ ~ ~'~ ~ [j ~
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<~' ~ ,.~ ~ :::3 ,_~
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.... ~.o ~ ~ ~ ~ ~ ^ ~
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~: ~.~ ~ ~ ~ ~ =x~ ~ ~ ~ .
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........ ~ ~: ~ ~ ~ 4= ::3 -, o .~ .~ >
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0..~ ~ ~ ~ ,-~
k~j~ cC ~ ~'~ = o~.~jn >'~
2 Vol. 3x4. B
18 J.G. WHITE AND OTHERS
-?
CAN-' ~ ú PLNR
- -- PVDL[ ASSOCIATED PDA1
ALA J LUMBAR '~
-- DA?.J
COMMISSURE i ..*---- ú ALNR
ú BDUL
SDQL PLN
SIADR I DORSAL
SIBDRI SUB-LATERALS
SMBDR I VD13
/
SMDDR__]
ASlO------~
DD6
VD12____,
ALML DB7 ~
'~ ALNL
VDll ~
AS9
VENTRAL
- CORD
DB4 ~ [ VDiO
-4---- ú PVDR
-- ~ ú PDER
D D 5 .~.~,,,~
. ASS ~ --
- DB6 ~
SIAVL1 VD9
SIBVR] VENTRAL
.,-- - SMBVL[-- SUB- LATERALS
SMDVR/-- AS7
/
PLNL _J --DORSAL
CORD
ALNL
-----~i ~ '4-'""-- ú CANL
~ ~ ú HSNR
J
nD4 ~ ~ ú CANR
---___ _ --
VENTRAL- DORSAL AS6-----~ --]
CORD CORD - S,AVR
J
SIBVL VENTRAL
S DQL-] -- ~ SMBVR SUB-LATERALS
/
ALNL~ SMDVL
PLNR
ALNR ú
ASS
ú 4,.-.------ ú PDEL AIf~{R
_ ~ ú SDQL VD6 ~ "'---'-- ú
DA6 ~ ~ ~ ú PVDL
- .,,,---------4) PVM DD3 __.~ ~ -4.-.-..---.-e AVM
AS4
ALMR l
ALNR
q VO5
PLM ~
- PLNLJ
VD4
t -
DB3
DD2 ~
DA2 -"/
.,~.........._ ú SDQR
ú BDUR
CANR ! CANAL
PVDR[ ASSOCIATED
J ^~ _1
VD3 ,,,
t '------- ú ALNL ~ -1
. SDQR
LUMBAR / ~ DA8 SI~Lll
-- SIBDL[l DORSAL
COMMISSURE AS1 ~ SMBDL-- SUB-LATERALS
4~---- ú PLNL ~ SMDD' '!
%J
ú PLML
L
r r
FIGURE. 7. For description see opposite.
THE MIND OF A WORM 19
cord is predominantly made up of these motoneuron axons but, in addition, has two processes
(from ALA and RID), which originate in the nerve ring and enter the dorsal cord at its anterior
extremity (figure 0). The nerve ring and the ventral and dorsal cords are the only process
bundles in which there are significant numbers of synaptic connections. The other distinguishing
feature of these process bundles is that they all run adjacent to ridges of hypodermis (figures
13, 18 and 19). Because the hypodermal ridge is situated on the left of the process bundle,
it may present a barrier on that side to commissures leaving the cord. This may be the reason
why most of the commissures run round the right-hand side of the animal.
In the anterior body there are four sub-laterally situated process bundles that run
underneath the body muscles (figure 6). They run in a straight line approximately corresponding
to the junction of the two rows of muscles in each quadrant. There are five processes in the
sub-lateral cords behind the nerve ring, and two in each of the cords in front of the ring
(figure 8). The processes in the anterior cords peter out in the head; those in the posterior
cord move to a more lateral position near the middle of the body, where most of them end
(figure 7).
Three nerve processes run for much of the length of the animal, closely associated with
the excretory canal (CAN-a). These processes run into the nerve ring at the anterior end
(figure 6) and peter out posteriorly in the tail.
The only remaining process bundles in the body are those made by the lateral touch receptor
neurons, ALM and PLM, and their associated neurons, ALN and PLN. The anterior touch
receptors, ALM, run in close association with ALN near the dorsal margin of the lateral
hypodermal ridges, whereas the posterior receptors, PLM, run along with PLN near the
ventral margin of the lateral hypodermal ridges. The processes of ALN maintain their
dorso-lateral location in the posterior part of the body although they are not in close association
with ALM in this region.
Musculature
Nematode body muscles are unusual in that their sarcomeres have an oblique conformation
with the actomyosin filaments, aligned at an angle of about 10c to the Z lines, rather than being
orthogonal to them. This type of arrangement has been referred to as obliquely striated muscle
(Rosenbluth 1965; Waterston et al. 1980). The Z lines consist of longitudinally oriented lines
of discrete structures (dense bodies), which are darkly staining in electron micrographs
(figure 18). These structures are roughly conical in shape; the base of the cone is adjacent to
DESCRIPTION OF FIGURE 7
FIGURE 7. Left-hand (a) and right-hand (b) process tracts in the body. The main process tracts are the ventral cord,
the dorsal cord, the excretory canal associated processes and the posteriorly directed sub-lateral processes. The
ventral cord consists of processes of interneurons and processes and cell bodies of motoneurons (figures 4 and
18). The ventral cord bifurcates at the anus and runs up to the lumbar ganglia via the lumbar commissures.
The dorsal cord (figure 19) is predominantly made up of motoneuron processes that have come from the ventral
cord via circumferential commissures, which are distributed along the length of the body. Most of the processes
in the posterior sub-lateral cords are derived from the nerve ring. These process bundles run sub-laterally under
the body muscles (figure 8) anteriorly, but move laterally to each side of the lateral hypodermal ridges where
most of the processes end. Processes from SDQ and PLN run into these cords from the opposite direction from
laterally situated cell bodies. The processes of CAN, ALA, PVD and also (in the anterior of the animal) BDU,
run together alongside the excretory cell for most of its length. The anterior touch receptors, ALM, together
with their associated neurons, ALN, run anteriorly near the dorsal side of the lateral hypodermal ridges; their
posterior counterparts, PLM and PLN, run anteriorly near the ventral side of the ridges.
2-2
FIGURE. 8. Most of the sub-lateral processes originate from the nerve ring and run longitudinally underneath the
muscle quadrants close to the line of apposition of the two muscle rows. Apart from a single NMJ, no synapses
have been seen on these processes. There are two processes in each of the sub-lateral cords anterior to the ring
(a) and five in each of the cords posterior to the ring (b). The individual processes run in fixed positions within
the cords. The posterior cords include processes from PLN and SDQ, which must have grown in the opposite
direction to the others, as their cell bodies are situated laterally in the body (figure 7). Apart from the processes
of these cells, the sublateral processes eventually peter out (figures 6 and 7).
THE MIND OF A WORM 21
the cell membrane, which is in turn adjacent to the hypodermis and cuticle. The body
muscles probably have attachments to the elastic cuticle distributed along their length,
since no specialized focal attachment points are seen at the end of these muscle cells.
Body muscles are rhomboid-shaped and are arranged as two parallel rows in each quadrant
(figure 10). There are 95 muscle cells in the adult; the left ventral quadrant contains 23 and
the other quadrants each contain 24: (Sulston & Horvitz 1977). The muscles in the body can
be divided up into three groups on the basis of their source of synaptic input: the anterior group
of four muscles in each quadrant, innervated by motoneurons in the nerve ring, the next group
of four, which is dually innervated by motoneurons in the nerve ring and ventral cord, and
the remaining muscles, which are innervated solely by the motoneurons of the ventral cord
(figure 10; see also Ware et al. (1975)).
Motoneurons of the ventral cord innervate either both dorsal or both ventral quadrants of
muscle. The body can therefore only propagate dorso-ventral waves during locomotion. The
head, on the other hand, can make lateral as well as dorso-ventral movements when the animal
is foraging. This is probably because the motoneurons in the nerve ring do not synapse onto
two quadrants of muscles, but instead are restricted to two adjacent rows (not necessarily in
the same quadrant). This would allow differential activation of muscles in adjacent quadrants
and possibly even in adjacent rows.
Nematode muscles are unusual in that they have neuron-like processes that run from the
muscle bellies to the neuron process bundles in which motoneuron axons reside (figures 9 and
18). Neuromuscular junctions (NMJs) are made by axons running along the surface of their
process bundle, through the bounding basal lamina of the bundle and onto muscle arms (see,
for example, VDn-a). Muscle arms interdigitate extensively and crowd round regions where
NMJs occur; there are often gap junctions between the arms in these regions. Muscle arms
in the body converge at the dorsal and ventral mid-lines, where they interdigitate, and contact
the dorsal and ventral cords (figure 9). Arms from the head muscles, which receive their
innervation from motoneurons in the nerve ring, run down past the outside of the ring and
then turn and run anteriorly, closely apposed to the inner surface of the ring. Here they sort
out in such a way that arms from each muscle row make an arc of about 45ø (figure 15). Thus
there is a mapping by the muscle arms of the spatial organization of the muscle cells onto the
inner surface of the nerve ring. Motoneuron axons run adjacent to the inside surface of the
ring and are arranged in a well-ordered pattern (figure 14). The inside surface of the muscle-
arm complex in the region of the NMJs is lined by the thin sheet-like processes of the GLR
cells (figures 14 and 15). No chemical synapses are seen on these cells, so they are probably
not neuronal; however, they do make gap junctions to muscle arms and to RME motoneurons
(figure 15).
There are sixteen sex-specific muscles in the hermaphrodite; eight are associated with the
uterus and eight with the vulva (figure 11). Unlike the body muscles, these muscles have focal
attachment points at their ends and do not have obliquely oriented sarcomeres. The
hermaphrodite gonad has twofold rotational symmetry, the axis of symmetry passing through
the centre of the vulva. The uterine muscles distal to the vulva, urn2, wrap round the uterus,
whereas the uterine muscles proximal to the vulva, uml, attach to the lateral lines. Both sets
of muscles consist of a pair of muscles that are joined at the ventral mid-line. There are two
sets of four vulval muscles, vml and vm2. The vml muscles are attached to the body wall
sub-ventrally, insinuating themselves between the rows of body muscles, and are attached at
J.G. WHITE AND OTHERS
DORSAL
CORD
VENTRAL
CORD
FIGURE 9. The body consists of a tube of hypodermal tissue made up of two cell types' the syncytial cell (SY), which
makes up the dorsal and ventral hypodermis, and the lateral seam cells (SE), which are also syncytial in the
adult and are joined to the syncytial cell by desmosomes. Longitudinal ridges of hypodeRmis run down the
body on the lateral, dorsal and ventral lines. Process bundles that make up the dorsal and ventral cords run
alongside the dorsal and ventral hypodermal ridges and are separated from the pseudocoelome by a basal
lamina. The body musculature consists of four quadrants of obliquely striated muscles. Each quadrant consists
of two closely apposed rows of muscle cells. The motoneurons that innervate body muscles have longitudinal
unbranched processes which are confined to the dorsal and ventral cords. Muscle cells send out processes to
the nerve cords, where motoneurons synapse onto them through the basal lamina at NMJs.
their proximal ends to the hypodermal lips of the vulva. The vm2 muscles attach to the body
more ventrally, at the ventral margin of the muscle quadrants, and are attached at their
proximal ends to the opening in the uterus, which connects to the vulva. Most of the synaptic
input to the vulval muscles comes from VCn and HSN neurons and is directed onto the vm2
muscles (figure 11 c). The other muscles are either directly or indirectly connected to vm2 via
gap junctions. The vmlR muscles send a muscle arm down to the ventral cord, where it receives
a small amount of synaptic input from ventral cord motoneurons.
Defecation is controlled by three sets of muscles: the anal depressor muscle, the sphincter
muscle and two laterally symmetric intestinal muscles (figure 12). The anal depressor muscle
is a large H-shaped muscle, which lifts the roof of the anus when it contracts. The sphincter
muscle is a circular muscle that closes off the end of the gut. The intestinal muscles have
longitudinally oriented filaments, which are situated in the ventral regions of the cells. The
dorsal regions flatten into thin sheets, which wrap round the posterior ventral regions of the
THE MIND OF A WORM 23
\
Excretory pore
DMR
DLR
ú ..~....._ ....:...:.:.:.:.:.:.: ...................... ..................... ...............
Right Lateral --
iiiiiiiiii}iiii~ ~i!jiiiiiiiiiiii!iiiiiiiiiiiiiiiiiiiiiiiiii L
iiiiiiiiiiii?iiiiiiii?ii~~~~
................. ,,,:,~iSiiiiiiiiiiiiiiiiiiiiiiiiili? ~~ ~ ~
:i:!:!:~:~:i:i::::::.:4.!.!.i.;.:.:.:~!~!!i~i:i:i:i:i:i:!:i:i:i:!:!:N:~:N:~:~::::::::::::::::::::::
iiiiiiii~iiiiiiii iiiiii--~
TM
.............................
Left Lateral
iiiii?iiiiiiiiiiiiiiiiii!iiiiiiii!iiii O L L
DML
...... '"'":~ Head muscles innervated in nerve ring
'":'"' "':" :" " :~ Neck muscles innervated in nerve ring and ventral cord
Body muscles innervated in ventral cord
FIGURE 10. 'Orange peel' projection of muscles in the head. The reconstruction was derived from electron
micrographs. The muscles are organized as longitudinal strips in each of the four body quadrants (figure 9).
Each quadrant has two adjacent rows of muscle cells. The muscles are obliquely striated and packed diagonally
so that the sarcomeres are oriented longitudinally. The first two muscle cells in the two ventral and two dorsal
rows are smaller than their lateral counterparts, giving a stagger to the packing of the two rows of cells in a
quadrant. The first four muscles in each quadrant are innervated exclusively by motoneurons in the nerve ring.
The second block of four muscles is dually innervated, receiving synaptic input from motoneurons in the nerve
ring and the anterior ventral cord. The rest of the muscles in the body are exclusively innervated by NMJs
in the dorsal and ventral cords (figure 9). The eight muscle rows have been labelled dorso-medial right (DMR),
dorso-lateral right (DLR), ventro-lateral right (VLR), ventro-medial right (VMR), ventro-medial left (VML),
ventro-lateral left (VLL), dorso-lateral left (DLL) and dorso-medial left (DML).
intestine and are probably attached to it. Muscle arms from these three sets of muscles run into
the pre-anal ganglion and are coupled together via gap junctions. Surprisingly little synaptic
input was found to be present on the defecation muscles, with only a single NMJ being made
by DVB.
Basal lamina
The pseudocoelomic cavity is lined with a thin (20 nm) basal lamina, which effectively
separates the muscles from the hypodermal and nervous tissues. This lamina has an anisotropic
structure, as parallel striations with a spacing of 30 nm can be seen when it is sectioned
obliquely (White et al. 1976). The gonad and the gut are ensheathed by similar basal laminae;
the pharynx is ensheathed by its own, rather thicker (4:5 nm) basal lamina (Albertson &
Thomson 1976). The dorsal and ventral nerve cords, together with their respective hypodermal
ridges, are bounded by the pseudocoelomic basal lamina (figures 18 and 10); the lateral
24 J.G. WHITE AND OTHERS
1j ulva--
vm2
r r
55 ~u55 v55~ v mtT:;:~
c
FIGURE 11. Egg laying is controlled by a set of sixteen muscle cells in the hermaphrodite, eight of which act to squeeze
the uterus (a) and eight to open the vulva (b). The distal uterine muscles, um2, form circumferential bands
of muscle round the distal regions of the uterus. The uml muscles attach to the lateral hypodermis and wrap
round the proximal ventral regions of the uterus. The vml muscles attach to the body hypodermis at the
ventro-lateral body muscle margins and at the vulval opening. The vm2 muscles attach to the body hypodermis
sub-laterally, insinuating themselves between the body muscles, and to the uterus at the vulval opening. The
vulval and uterine muscles have gap junctions to each other, as shown in (c). The main synaptic input is onto
the vm2 muscles and comes fromVCn (*a) and HSN (*a). The NMJs are dorsal to the main part of the ventral
cord (VCn-a). vmlR sends an arm down into the ventral cord and receives single synapses from VD7, VB0
and VA7.
In estine Sphincter muscle
muscle
Intestinal muscle
FIGURE 12. There are three muscles directly involved in defecation: the anal depressor muscle, the anal sphincter
muscle and the two intestinal muscles. The anal depressor muscle is a large H-shaped cell, which lifts the
posterior dorsal surface of the rectum so as to open it and discharge its contents. The intestinal muscles have
longitudinally oriented contractile filaments and attach to the body hypodermis at the ventral muscle margin
and to the intestine via several distributed contacts on its ventral surface. The intestinal and depressor muscles
send muscle arms to the posterior regions of the pre-anal ganglion, where they receive synaptic input from DVB
(*c).
hypodermal ridges and the laterally located ganglia are similarly bounded. The boundary
curves smoothly, suggesting that the lamina may be under tension in these regions.
All the nervous system is situated to one side of the pseudocoelomic basal lamina, with the
exception of the cell bodies of URX, CEPD and GLR. The processes of URX and CEPD run
together on each side as they leave the ring sub-dorsally. They are surrounded by, and
eventually penetrate, the basal lamina in these regions before reaching their cell bodies, which
are situated in the pseudocoelomic cavity. The basal lamina may also be penetrated in four
places on the inside of the nerve ring by muscle arms (figure 14 and RIM-d). This enables
THE MIND OF A WORM 25
a motoneuron (RIM), which has its axon buried in the interior of the ring neuropile, to make
NMJs.
Nerve processes seem to be constrained to run alongside the lamina. Processes that run from
the ventral to the dorsal cord, for example, run round the animal, travelling underneath the
muscle quadrants instead of taking a more direct internal route. In the main part of the body
cavity the dorsal and ventral ridges are quite small, consisting of a ridge of hypodermis and
an adjacent process bundle (figure 13d). As the head is approached, the dorsal, ventral and
lateral ridges enlarge as they become filled with the cell bodies of their respective ganglia
(figure 13c). Eventually the basal laminae bounding the four ridges meet and fuse (figure 13b).
An internal tract is now opened up and processes course round it inside the muscle quadrants
forming the nerve ring. This organization is maintained up to the tip of the head with the four
muscle quadrants running in tubes of basal laminae (figure 13a). The central ring of lamina
left after the ridges have fused ends in the vicinity of the nerve ring. It appears to terminate
on the cylinder that is made up of the sheet-like processes of the GLR cells. This structure is
situated on the inside of the nerve ring between the pharynx and the muscle arms.
The arrangement of the basal lamina lining the pseudocoelome suggests that it may be
instrumental in the establishment of the general topography of process tracts in the nervous
system. Processes from neurons have been shown to grow preferentially along ordered fibrillar
arrays (Weiss 1934). The striated structure may likewise serve to guide initial process
outgrowths, thereby establishing the antero-posterior and circumferential system of process
bundles that are a feature of the nervous system of C. elegans.
Neurons
Branching structure
The component neurons of the nervous system of C. elegans have simple, unbranched
morphologies. Few neurons have more than two processes, and many are monopolar with only
a single process (see, for example, AIA). Processes of neurons run in parallel bundles except
in the immediate vicinity of their cell bodies, where they join the bundle. This region is not
extensive, however, as cell bodies are generally situated close to the bundle into which they
project. Branching typically occurs when a neuron has a process that leaves the main bundle
to run out as a commissure (see, for example, VDn), or at a discontinuity, where one bundle
joins another (as in AQR where it leaves the ventral cord and enters the nerve ring).
Neurons with a branched structure generally have very similar patterns of branching in
different animals; however, there are a few interesting cases where differences occur between
animals, or between sides of the same animal. The interneuron RID lies on the dorsal mid-line
and sends a process round the left-hand side of the nerve ring in the N2U animal and round
the right-hand side in the JSH animal. The nerve ring has a high degree of bilateral symmetry
and the process of RID runs in a similar position relative to the neighbouring processes whether
it runs on the left or the right.
The interneuron PVN is the most highly branched class of neuron in C. elegans. The main
processes of PVN run up the ventral cord and enter the nerve ring on the right-hand side,
travelling round it in an anticlockwise direction. PVNL has an additional branch, which
separates from the main process at a point behind the excretory duct. This branch enters the
ring on the left-hand side, travelling round it in a clockwise direction. This process (which is
not present on PVNR) runs in the same region of neuropile as do the main processes of both
26 J.G. WHITE AND OTHERS
MUSCLES
HYPODERMIS
r r
DORSAL
GANGLION
.'
:...! :'.-.' ....
r @
//////---. ~. vou ~.~
FIGURE 13. The pseudocoelome in the body is bounded by a basal lamina, which covers all the hypodermal and
nervous tissue (d). The muscles are in the pseudocoelomic cavity. Processes of neurons do not, in general, cross
the basal lamina. Commissures between the dorsal and ventral cords pass underneath the muscle quadrants
and do not enter the pseudocoelomic cavity. As the ring is approached, the dorsal, ventral and lateral cords
enlarge where they are filled with cell bodies of the respective ganglia (c). There is no direct route between
the ganglia at this point, however, and cell bodies in the lateral ganglia send processes into the ventral cord
via the amphidial commissures (figure 6). At the level of the nerve ring, the lobes of the basal lamina fuse inside
the muscle quadrants (b) allowing the processes in the nerve ring to run round without having to pass
underneath the muscle quadrants. The processes of the nerve ring, like those of the nerve cords, run alongside
a ridge of hypodermis (a), which is anterior to the neuropile. The nerve ring seals off the anterior end of the
pseudocoelomic cavity and there is no basal lamina bounding the hypodermal and nervous tissue in the head,
except for that bounding the pharynx.
PVNR and PVNL, which are travelling in the opposite direction; they also make similar
synaptic contacts. Other examples of such conservative variation in branching patterns have
previously been noted in the cephalic receptor neurons, CEP (Sulston et al. 1975). These
observations suggest that, irrespective of branching structure or even direction of growth, a
process is capable of locating its appropriate neighbourhood within the neuropile and forming
its characteristic synaptic connections.
THE MIND OF A WORM 27
A few examples of non-conservative changes in branching pattern have been seen. A fairly
major branch is missing on RMFR in the NgU animal but is present on its contralateral
partner and is also present on RMFR in the JSH animal. As the missing process has all the
NMJs made by this motoneuron, such a change must have a profound effect on the function
of RMFR in this instance. It seems reasonable to consider such incidences of branching failures
as developmental errors in the construction of the nervous system, which could perhaps give
rise to non-genetically related variations in behaviour between animals.
Branch termination
The processes of many classes of neuron terminate at the point of contact with a process from
a neighbouring member of the same class. There is usually a gap junction at this point (as in
ASI on the dorsal mid-line), although there is one case where processes touch and terminate with
no gap junction (RIF). There are also a few cases where such contact terminations can occur
between heterologous classes (e.g. between processes of ALM and AVM in the nerve ring).
The most striking examples of contact termination are exhibited by the DDn and the VDn
motoneurons of the ventral cord. There are six DDns and thirteen VDns evenly distributed
along the length of the cord. Each of these classes has processes in both ventral and dorsal cords.
Together, their processes make an unbroken line of non-overlapping processes in each cord
(White et al. 1976). This behaviour seems to be an intrinsic property of certain classes of
neuron; other classes of neuron make contacts and gap junctions with members of their own
class but do not terminate at the site of initial contact and may have considerable overlap (see,
for example, ASE, AIN).
Gap junctions
Gap junctions are organelles that mediate electrical and metabolic coupling, between cells
(Bennett 1977)- They are seen in C. elegans as regions where the membranes from two adjacent
cells are closely apposed and appear more darkly staining than surrounding regions (as in
VBn-c). When gap junctions are sectioned transversely, a gap of about 8 nm can be seen
separating the membranes. The region of close apposition is usually in the form of a plaque
of about 350 nm diameter. The membranes at the junction are notably flatter than those of
the surrounding regions. The gap junctions seen in C. elegans resemble those described by
Pappas & Waxman (1972).
Gap junctions are seen between muscle cells and between neurons. Apart from a couple of
possible exceptions (RMD-h and VCn-f), gap junctions are not seen between muscle cells and
neurons, probably because there is usually a basal lamina separating the two. The glial-like
cells, GLR, are unique in that they make gap junctions to both muscles (GLR-c) and neurons
(GLR-d). They do not, however, make gap junctions to themselves. The arrangement of these
gap junctions is shown in figure 15.
Muscle arms from muscles in the head have a striking arrangement of gap junctions where
they interdigitate at the inside of the nerve ring. Arms make gap junctions with arms from
muscle cells in adjacent quadrants but not with arms from muscle cells in the same quadrant,
even though both sets of arms are equally accessible (figure 15). Muscles in the same quadrant
are, however, connected by gap junctions, but the connections are situated in the region of
the muscle cell bellies, well away from the arms. Thus it seems as though muscle arms, when
they grow into the nerve ring, can discriminate between the arms of muscle cells that are
already connected to themselves via gap junctions and those that are not.
28 J.G. WHITE AND OTHERS
Chemical synapses
Chemical synapses in C. elegans occur en passant between neighbouring parallel processes. The
presynaptic process has a vesicle-filled varicosity and a specialized, darkly staining region in
the membrane adjacent to the point of contact with the postsynaptic elements (see, for example,
BAG-a). A considerable variation in the size of the presynaptic regions was found (compare
OLQ-a with PVN-a). The presynaptic specializations also vary in prominence between
different classes of synaptic contact in a way that does not necessarily correspond to the size
or the number of vesicles in the presynaptic process. The extremes of this variation are
represented by RIP, on the one hand, which has structures that look like presynaptic
specializations but with no associated synaptic vesicles (RIP-a); and, on the other, by DVA,
which has large vesicle-filled varicosities but rather small presynaptic specializations (DVA-b).
There is also considerable variation in the number of chemical synapses between pairs of
interacting processes. There are many cases where there is only a single synapse present. At
the other end of the scale, the largest number of synapses seen between processes is nineteen
(AVDL onto AVAR); more typically it is around five. Some of the single synapses that are
seen are small, with few synaptic vesicles or indistinct presynaptic specializations. Synapses of
this type are also rather variable, in that they are not present in some individuals and therefore
probably not very significant. On the other hand, some single synapses are large, with many
vesicles and unambiguous presynaptic specializations. These synapses are seen in all individuals
and so are probably significant. This latter type of synapse seems to occur when the layout
of the two interacting processes is such that they are only adjacent for a limited extent. In these
cases there may only be room for a single synapse in the region where the two processes are
adjacent.
Although the fixation and staining procedures that were used are not optimal for the
preservation and visualization of vesicle morphology, several classes of vesicle can be clearly
distinguished. The most ubiquitous vesicles are spherical, 35 nm in diameter, and have lightly
staining interiors (see, for example, RIA-a). Some classes of neuron, including most of the
amphid receptors, have a second class of vesicle coexisting with vesicles of this first type. These
vesicles are larger and have darkly staining cores (as in ASK-a); the relative proportions of
the two types of vesicle varies with cell class. There is a certain amount of variation in the
staining properties of these dark-cored vesicles between classes; the sizes also vary, ranging from
37 nm (ASE) to 53 nm (ASK). The dark-cored vesicles seem generally to be excluded from
the region immediately adjacent to the presynaptic specialization, which contains only the
smaller type of vesicle. A similar segregation of vesicle types is exhibited by DVA, which has
a large process in the nerve ring, filled with irregularly shaped vesicles, but has small spherical
vesicles next to presynaptic specializations (DVA-a). The neurotransmitters that may be
contained in the dark-cored vesicles are not known. Dopamine has been shown to be present
in CEP, ADE and PDE neurons (Sulston et al. 1975). Acetylcholine is probably used as a
neurotransmitter by the ventral cord motoneurons VAn, VBn, DAn, DBn and ASn, as this
transmitter has been shown to be used in the equivalent neurons in Ascaris (Johnson & Stretton
1980). All these classes of neuron have uniform populations of spherical, 35 nm, synaptic
vesicles, with no dark-cored vesicles present (see, for example, CEP-a, VAn-a).
Chemical synapses in C. elegans usually have no visible specializations on postsynaptic
elements and consequently there is often some ambiguity as to the identities of these elements.
THE MIND OF A WORM 29
In some cases, the disposition of the processes is such that there clearly can be only one
postsynaptic element (as in ASE-a). In many other cases there are two (for example, in ADF-a)
or, more rarely, three (for example, in AIY-e) postsynaptic elements, making a dyadic or
triadic synapse (Dowling & Boycott 1966). It was difficult to know in these cases whether all
the postsynaptic elements are functional (i.e. have an appropriate receptor) or are just
neighbouring processes. It seems likely that, in many cases, all the possible postsynaptic
elements could be functional, as particular dyadic or triadic combinations are found to occur
in many instances (for example, AIA and AIB are often the two postsynaptic elements in a
dyadic synapse). Some synaptic pairings are only seen in the context of multiple synapses.
Although this may suggest that such a pairing could be non-functional, there are cases where
this cannot be so, as the other postsynaptic element of the dyadic synapse is also seen only in
the context of a multiple synapse (for example, RIB and AVE are postsynaptic to AUA, and
AVE and AIZ are postsynaptic to RIG). This observation raises the interesting possibility that,
in some cases, synaptogenesis may be dependent on the simultaneous presence of two particular
postsynaptic elements.
Several process pairs are seen to synapse onto each other reciprocally. AVAL/R and
PVCL/R synapse onto each other along the length of the ventral cord, for example, but there
is no particular spatial relation between the two types of synapse. The reciprocal synapses made
by RIA and RMD are usually situated close to each other, however, making a characteristic
structure (RIA-e). Such an organization may provide positive or negative feedback in these
synaptic connections.
Many classes of neuron are found to have regions of process that are devoid of presynaptic
specializations. This could be because the particular class of neuron does not have many
synapses in total or that these regions corresponded to regions where there are no suitable
postsynaptic partners. In several cases neither of these explanations can be valid. The
interneurons AVA, AVB, AVD and AVE are all exclusively postsynaptic in the nerve ring,
yet they have extensive synaptic outputs in the ventral cord. Furthermore, AVD, AVE and
AVB all have extensive synapses onto AVA along the cord; however, in the nerve ring,
processes from these cells do not make such synapses even though they are accessible to AVA
(i.e. are adjacent to its processes) for part of their extent within the ring. Thus it appears that
certain classes of neuron can localize the regions where they are presynaptic. Those regions
of process that are devoid of presynaptic contacts are often more lightly stained than adjacent
processes (AVA-a). There seems to be no localization of postsynaptic contacts.
Occasionally, presynaptic elements are seen with no obvious postsynaptic partner, or with
a hypodermal cell as the only possible partner. AVB is particularly prone to this behaviour,
having six such structures along the length of the ventral cord (see, for example, AVB-a). It
is difficult to know how to interpret these structures; they could possibly be functional synapses
and control some hypodermal cell function such as cuticle deposition or moulting, or they could
be artefacts.
Neuromuscular junctions
Neuromuscular junctions (NMJs) are special cases of chemical synapses where at least one
of the postsynaptic elements is muscle. As the muscle and nervous system are situated on
opposite sides of the pseudocoelomic basal lamina, NMJs have to pass through the lamina with
the presynaptic elements (the motoneuron axons) on one side and the main postsynaptic
30 J.G. WHITE AND OTHERS
elements (the muscle arms) on the other. Because of this arrangement, NMJs are constrained
to lie on the two-dimensional surface of the lamina. NMJs usually have several postsynaptic
elements. On the inside of the nerve ring, there is a continuous plexus of arms from muscles
in the head and a high density of NMJs (figure 14). In the ventral cord, the NMJs are more
dispersed and muscle arms crowd round and interdigitate at foci where there are presynaptic
elaborations on motoneuron axons (figure 18).
Certain classes of neuron (VDn, DDn, RMD, SMD, RME and RIP) have processes that
are postsynaptic at NMJs. These processes are on the same side of the basal lamina as the
presynaptic elements and often have a short branch, which dips in and intercepts the NMJ
(see, for example, RMD-a). Because of this behaviour, it seems likely that these processes are
functional postsynaptic elements. The disposition of the dendritic processes relative to the
NMJs that they are intercepting suggests that the NMJs might have formed first and the
dendrites might have moved in and insinuated themselves into position later. There is likely
to be some specificity as to which NMJs are intercepted by particular dendrites, as dendrites
along the ventral cord are not associated with the NMJs of VDn and DDn, but are associated
with the NMJs of the other motoneuron classes active in the nerve cord, even though all classes
of NMJ are equally accessible to the dendritic processes.
With the exception of RIP, all the classes of neuron that have postsynaptic elements in NMJs
are motoneurons themselves and, interestingly, have NMJs on the diametrically opposite side
of the animal to the regions where they are postsynaptic. Thus it seems likely that these classes
of neuron act as cross-inhibitors, ensuring that muscle contractions in diametrically opposite
regions of the animal operate in antiphase. Neurons analogous to VDn and DDn have been
identified in the ventral cord of A. lumbricoides and have been shown to be inhibitory (Johnson
& Stretton 1980).
The arrangement of motoneuron axons around the inside surface of the nerve ring was found
to be the most highly ordered region of neuropile in the nervous system (figure 14.). The ordering
is such that it is often possible to identify many of the processes in this region by their
appearance in a single appropriately positioned section. Several of the NMJs in this region are
organized as characteristic complexes made up of presynaptic endings clustered around a
dendritic process (figure 14). The dendritic processes are from RMD, SMD and RIP. The NMJs
made by RMD and SMD are situated diametrically opposite their dendritic processes. The
RIP neurons also have processes that cross over to the diametrically opposite side from the
dendritic regions, even though they are not motoneurons. These processes eventually enter
the pharynx (Ward et al. I975; Albertson & Thomson 1976).
The arms from each row of head muscles are arranged around the inside surface of the nerve
ring such that arms from each row occupy a well-defined arc. This arc is positioned in an
equivalent location to that of the muscle row from which the arms originated (figure 15). There
is thus a fairly precise mapping of the circumferential positions of the muscle rows, by the
muscle arms, onto the motor endplate region. The ordering of the motoneuron axons on one
side of the basal lamina and the muscle arms on the other is highest at the regions immediately
adjacent to the lamina but is less apparent away from it.
The flattened processes of the GLR cells cover the inside surface of the plexus of muscle arms
inside the nerve ring and are seen to have gap junctions with adjacent muscle arms (figure 15).
The processes of GLR are found to be aligned with the arcs of muscle arms from each row
(figure 14). The sub-dorsal and sub-ventral sets (GLRDL/R and GLRVL/R) are each
THE MIND OF A WORM 31
associated with muscle arms from one row, whereas the lateral pair (GLRL/R) are larger in
circumference and are each associated with two muscle rows. The points of contact between
adjacent GLR processes are closely aligned with the points of contact of the arcs of muscle arms,
except in the case of the muscle rows lying either side of the lateral lines. In these, there is no
GLR process junction and a certain amount of mixing of the muscle arms at the point of contact
of adjacent arcs occurs, whereas there is no mixing at the points of contact that have an
associated GLR process junction. These observations suggest that the GLR processes may act
to guide muscle arms and confine them to their appropriate territories on the inside of the nerve
ring.
RMEV
RMDDL
SMDVR
SMBDL
RMDVR
L2DR
R
MDL
ML
GLRDR RMED -- RMGR
ILIDR
~RMFL
RIPR
~RMHL
URADR --RMDR
RMDDL LIR
GLR --RMEL
IL2L~
RM --------- G L R L
I
R
RMH MDVR
RMF LlVL
MDDL
GLRVL
RMGL --
RIMR~
RM
RMDDL
OLQVL ~ .......
IL2VL MUSCLE ARMS
SMBVR
RMDVR RMED
FIGURE 14. Neuromuscular junctions in the nerve ring. The eight rows of muscles in the head and neck (figure 10)
have muscle arms that project onto the inside surface of the nerve ring in a highly ordered way (figure 15).
They are sandwiched between the thin sheet-like processes of GLR cells on the inside and the motoneurons
of the nerve ring on the outside. Four spurs of muscle arm penetrate into the anterior neuropile of the ring
sub-laterally and receive synaptic inputs from RIM, which runs in the interior of the ring neuropile. The other
classes of motoneuron form complex, but well-defined, structures adjacent to the inner surface of the nerve ring.
Most NMJs are dyadic, with dendrites of other motoneuron classes or RIP as the corecipients. The dots in
the processes show the locations of the presynaptic specializations.
One motoneuron, RIM, is unusual in that it does not have its axon adjacent to the inside
surface of the nerve ring. Instead it forms NMJs onto four spurs of muscle arms that invade
the neuropile of the ring (figure 14:). It is difficult to visualize the basal lamina in these regions,
so it is not clear whether the muscle arms actually penetrate the basal lamina at these points
or whether the basal lamina is herniated. The sites of these invaginations again correspond to
junctions between GLR processes and are fairly small; muscle arms anterior and posterior to
these regions run along the inside surface of the ring.
32 J.G. WHITE AND OTHERS
DORSAL
/
/
., /
FIGURE. 15. Head and neck muscle projections. The muscle arms from the 32 head and neck muscles send arms
posteriorly past the outside surface of the nerve ring. These then turn and run anteriorly onto the inside surface
of the ring. The muscle arms are highly ordered in this region and map onto the inside surface according to
the circumferential location of the muscle bellies. Muscle arms have gap junctions to arms from adjacent
muscles in neighbouring quadrants and to GLR cells. RME motoneurons also have gap junctions to GLR cells
in the arrangement shown. There are gap junctions between the muscle bellies of muscles in adjacent rows
of the same quadrant but, interestingly, none are seen between the arms from these muscles, even though they
interdigitate extensively.
There are seven main classes of motoneuron in the ventral cord' VAn, DAn, VBn, DBn,
ASn, VDn and DDn. Members of each class are evenly distributed along the length of the
cord (White et al. 1976). Within each class there are sharply defined transition points where
one axon becomes synaptically active, having many NMJs along the cord, and the adjacent
axon becomes inactive, having no more NMJs. These transition points occur in slightly
different positions for each class; such observations suggest that there might be intraclass
competition for territory along the ventral cord (White et al. 1976). Similar intraclass
competitions for territories have been shown to occur in two dimensions for classes of ganglion
cell in the vertebrate retina (Wassle et al. 1981). In the nerve ring, many of the motoneuron
classes have NMJs at discrete points around the motor endplate region and so it seems unlikely
that intraclass competition has a role in establishing NMJ territories in these cases. The
RMDD/V motoneurons have NMJs around the whole circumference of the ring, however, with
abrupt transitions between adjacent class members, which each have NMJs over a 45ø arc.
Thus it seems possible that, in this case, intraclass competition may be used to partition out
territory for NMJs to the class members.
THE MIND OF A WORM 33
The organization of processes within bundles
The process bundles in C. elegans are spatially ordered, with processes running in characteristic
positions within the bundle and maintaining their locations relative to their immediate
neighbours over long distances. This ordering is independent of the size of the process bundle.
For example, the four anterior sub-lateral cords, which are made up of only two processes, each
have the same relative disposition of processes (figure 7). On the other hand, the ventral cord
near the junction of the nerve ring is made up of about 170 processes; it is bilaterally symmetric
in this region and the degree of order that was found can be seen by comparing the positions
of bilaterally symmetrical processes on each side of the cord (figure 16b). There is a little more
variability seen between the cords of different animals of the same genotype and developmental
stage than between each side of the cord in a single animal. Although the order of processes
in the cord is maintained over long distances, local mechanical intrusions, such as cell bodies,
can disturb the ordering temporarily, but order returns away from these regions.
Processes that must have grown in opposite directions are found to be freely mixed within
process bundles. The processes of PVQR and PVPR in the ventral cord, for example, must
have grown up from their cell bodies in the tail, yet most of their surrounding processes,
such as those of AVAL, HSNR and AVJL (figure 18b), have their cell bodies in the head and
their processes must therefore have grown in opposite directions to those of PVQ and PVP. The
relative positions of adjacent processes that had grown in opposite directions was fairly constant
over long distances. Such an organization of processes might conceivably have arisen by
rapid and sequential process growth; in other words, each process would grow along the full
length of the process bundle before its neighbour growing in the opposite direction started out.
A more likely explanation for these observations is that processes can insinuate themselves
in between pre-existing processes in a bundle and follow along specific neighbours. The
observation that the processes of PVNL in the left sub-dorsal region of the nerve ring must
have grown in opposite directions, but nevertheless, ran in the same region of the nerve ring,
supports this latter interpretation.
Any individual process in a bundle has a group of adjacent processes that immediately
surround it at any point. We refer to such a group as the neighbourhood of the process.
Neighbourhoods are generally fairly constant over the length of processes, reflecting the
ordered arrangement of processes within bundles. Certain neighbours are found to be much
more persistent than others, however, always remaining adjacent, whereas others move in and
out of direct adjacency along the length of the process (White et al. 1983). In some instances,
groups of processes are seen to be closely associated together; the most striking example of this
behaviour is shown by the dendritic regions of RMD motoneurons, which are clustered around
the processes of RIA (RMD-d). In this particular case there are extensive synaptic interactions
between RIA and RMD, but in other cases, such as the close association of ALM and ALN
on the lateral lines (ALN-d), there are no synaptic interactions between the associated
processes.
Many processes make abrupt changes of neighbourhood at certain points. The processes of
AIB are closely associated with those of AIA on the ipsilateral side, but at the point where the
latter terminate, on the dorsal mid-line, the processes of AIB turn and run across the process
bundle. They then run for a short distance anteriorly before turning again and continuing on
their trajectories round the ring; they are now in a different neighbourhood, where they run
3 Vol. 3 I4. B
34 J.G. WHITE AND OTHERS
!!! .........
FIGURE 16(a). For description see opposite.
THE MIND OF A WORM 35
3-2
36 J.G. WHITE AND OTHERS
in close association with the processes of RIM (White et al. 1983). Such major changes of
neighbourhood obviously have considerable functional significance for a neuron as they
provide an extended set of possible synaptic partners. Perhaps, more significantly, they also
facilitate direct communication between non-adjacent neighbourhoods.
In many (but not all) cases, there are external discontinuities at the transition points between
neighbourhoods. The greatest numbers of neighbourhood transitions are seen to occur at the
junction of two process bundles. In the region where the amphid commissure (figure 17) joins
the anterior ventral cord (figure 16b), most processes from the commissure make transitions
of neighbourhood (as in ASG) although some neighbours are maintained (as in AIB/AWC).
The same type of behaviour occurs at the junction of the ventral cord and the nerve ring
(figures 16 and 20), with some processes maintaining their neighbourhoods (see, for example,
ASJ/PVO_JASK) while others (e.g. ASH) switch. A discontinuity of a different type is seen
on the dorsal mid-line of the nerve ring, which corresponds to the points where AIB, AVE and
AVD make abrupt transitions of neighbourhood. In this case the discontinuity is apparently
due to the termination of many processes in this region (notably the amphid receptor neurons),
usually in gap junctions to their symmetrical analogues (e.g. ASJ-c). AIB and AVE are both
closely associated with processes that terminate in this way in one of their neighbourhoods. In
AVD, the associated processes are not obvious and it appears that the processes of AVD may
have been deflected by a process emanating out of the cell body of RID (AVD-e).
Motoneurons are generally found to inhabit two neighbourhoods. One corresponds to the
region where the motoneuron is predominantly or exclusively postsynaptic, usually in the
interior of a process bundle, and the other is the region where NMJs are situated, at the surface
ora process bundle adjacent to the basal lamina. The transitions between these neighbourhoods
are not accompanied by obvious external discontinuities in most cases, except for a similar
transition occurring in an adjacent motoneuron of the same class.
Groups of processes that are fasciculated together have been shown to share a common
antigenic determinant in the leech (Hockfield & McKay 1983) and the grasshopper (Raper
et al. 1983). It is possible that such antigens are neighbourhood-specific adhesion molecules.
Such specific adhesion molecules, or perhaps a single ubiquitous molecule, such as CAM, which
is spatially and temporally regulated (Edelman 1983), may be the basis for the close associa-
tions of groups of processes seen in the nervous system of C. elegans. It is interesting to consider
the abrupt changes in neighbourhood exhibited by some neurons in the context of inter-process
adhesivity. In the switches in neighbourhood that Occur at process bundle junctions, it seems
likely that mechanical disturbances have mixed the processes, introducing them to novel
neighbours. Some of these neighbours may have high adhesive affinities for the newly
introduced processes and act to guide and establish the processes in their new territory. Such
a notion carries the implication that specific neighbourhoods are not uniquely attractive for
a particular process, but rather that there may be several neighbourhoods in which a process
could equally well reside, the one selected being dependent on the initial placement of the
process in the bundle. In general there are few directed movements of neurons relative to their
neighbours after they are born (Sulston 1983). It therefore seems that the initial placement
of a neuron at birth is the major factor that determines which neighbourhood is finally selected
out of the set of neighbourhoods in which its process could equally well reside.
The neighbourhood transitions exhibited by motoneurons seem to be mediated by factors
that are intrinsic to the neuron. Other neurons, such as AVA and AVB, show a clear
THE MIND OF A WORM 37
FIGURE. 18. Transverse section through the ventral cord (above) and process identifications (below). The ventral
cord consists of a process bundle that runs alongside a longitudinal ridge of hypodermis; the whole structure
is bounded by a thin basal lamina (BL). Axons of motoneurons arrange themselves next to the basal lamina
on the right-hand side of the cord in a fixed arrangement. The usual sequence of motoneuron classes from dorsal
to ventral is VCn, VDn, DDn, VAn, and VBn. NMJs are made in this region (one from a VD3 is seen in this
section); the motoneurons synapse through the basal lamina onto muscle arms (MA) from both left and right
ventral muscle quadrants. The NMJs of a motoneuron are in a well-defined region along its process; outside
this region, the process moves away from the basal lamina to the ventral regions of the process bundle. The
VDn and DDn neurons are an exception in that their processes terminate abruptly outside the NMJ regions.
The cell bodies of the motoneurons that innervate body muscles are arranged in a linear sequence in the ventral
cord (figure 4). The ventral cord also contains the interneurons that synapse onto these motoneurons and other
interneurons with little or no synaptic activity in the cord. The arrangement of processes in the cord is fairly
consistent along the length of the cord, although there may be local distortions. Fingers of hypodermis (HDC)
often project from hypodermal cells and run along the cord for short distances. Muscle cells have darkly
staining, conical, dense bodies (DB) in the Z bands.
FIGURE 19. Transverse section through the dorsal cord (above) and process identifications (below). The dorsal cord
is similar in overall structure to the ventral cord but is much simpler, as it has fewer processes and no cell bodies.
The processes in the dorsal cord are all motoneuron axones except for the processes of VDn and RMED. DAn,
DBn, ASn, DDn and VDn all have processes in the dorsal cord that originate from cell bodies in the ventral
cord via circumferential commissures (figure 7). RID sends,a process along the length of dorsal cord from its
cell body, which is situated in the dorsal ganglion.
differentiation of their processes into regions that are both pre- and postsynaptic, and regions
that are exclusively postsynaptic. In the case of motoneurons it is not clear whether there are
no synapses made by the axon when it is in the interior of the process bundle because there
are no suitable postsynaptic targets (muscle arms) available in the neighbourhood, or whether
this region of the process is intrinsically incapable of supporting synapses. If this latter
interpretation is correct, it may be that particular adhesion factors are also associated with these
differentiated regions of the process. A factor that was localized in presynaptic regions that
conferred an adhesive affinity with the basal lamina could, for example, serve to constrain the
process to run alongside the basal lamina in these regions.
40 J.G. WHITE AND OTHERS
RMER I
R I~~DL :;o
'L2L
RMEL
RMDR
RI~ ~.._~ ~RMED
AVK -------- R M DVR
RIVR v - -
lA,.
lB,
SAADL
-------- S M DD L
i ~SIAVL
SMDVR~ R I~ø
---------~ S I AVL
SIBDL~ R/BL Ix~~ -- SMBVL
- ,,,,.,.
AVA L A Q R ~ PVC R
AUAL~ --GLRL
~,.. o~%~~ .~.s..
-~BDUL
PVNL
ASEL
~SMBVL
AVFR
AVFL
--AVEL
AVA L
C }
ADLL
›
AFDL
FIGURE 20. Reconstructed cross sections of neuropile of nerve ring; (a) left lateral, (b) right lateral, (c) dorsal and
(d) ventral. These drawings were obtained by reconstructing pictures of transverse sections of the nerve ring,
so there are no single corresponding electron micrographs. The large outlines peripheral to the neuropile
are cell bodies. The relative disposition of processes in the nerve ring is relatively constant; several processes
can usually be identified directly from an electron micrograph by their morphology and position in the process
bundle. The axonal regions of motoneurons are situated adjacent to the anterior inner surface of the nerve
ring and synapse onto muscle arms through a basal lamina. The processes of GLR cells flatten out in this region
and form a cylinder on the inside of the muscle arms. The neuropile of the ring is fairly regionalized; the amphid
receptors and their associated interneurons have processes in the posterior of the ring, the neurons that make
up the sub-lateral cords have their processes in the centre and the mechanoreceptors tend to have processes
in the anterior regions.
THE MIND OF A WORM 41
(b) ~ ,LIR )
URBR
BAGR
AVEL ~ RMER
RIBR
RMDVR--
RMDDR~ DV
-----------AV K L
DV I
.~RMHR
RIVL
RMœR
SMDDR
SMBVR ~ ~ I//..
- --------- S I B DR
CEPDR ~ -
RICR~
AVJ L-- -
SMBVR~
AV F R~-~ [ b'4q I~,.,,.~ IAA~~,~q3` /_~
AWBR~ ~ RMDVR
ASKR A LA
AVER AVAR
AFDR
FIGURE 20 (b). For description see opposite.
Circuitry
We have summarized the connectivity data of the neurons detailed in Appendix 1 into a
set of connectivity diagrams (figure 21 a-f). In these diagrams, we have lumped together all
members of a class and considered the connectivity of the class as a whole. Connectivity was
used as one of the main criteria for grouping neurons into classes and so, by definition, all
42 J.G. WHITE AND OTHERS
(c) OLL.~ /,L,[,
~L,D--fi .,ED ~CEsD.
RMDVRx I I MUSCLE '~ / ~ RIBL il
RMD ~ RMFR
RMHL~ -'""~'~i'"'"'~ ~/"~/4~1~~~r ~ RIMR 1
RIC 3
RMDD
V
SIBV
~- - SAADL
RI 3~~j~O~/~v t $MDVLL
SMB
SIB :t *
FCEPshDL DV
Ap~/HRL~ J~~ R
PVPL ~~AIBR
AFDR
- AIBL ASER
GLRDL ~'~
ALA
URXL
CEPshDL
FIGURE 20 (C). For decription see page 40~...
neurons within a class have the same, or very similar, patterns of connectivity to members of
other classes. Thus such class groupings considerably simplify the circuit diagrams but at the
expense of obscuring intraclass differences in synaptic connectivity. Such differences do not
break class rules but specify which particular member of a class synapses to which particular
member of another class.
The connections between classes that are shown are those that are considered to be
THE MIND OF A WORM 43
(d)
ILlVL
GLRVR
CEPVR
CEPVL
..,v.
CEPshVI
RMED
RMEV
FIGURE; 20 (d). For description see page 40.
significant. In addition, some indication has been given of the relative prominence of chemical
synapses. A number of criteria were considered when making these judgements. For chemical
synapses, the numbers and sizes of the synapses in a particular connection were taken into
account. In marginal cases, where there were only one or a few small synapses, consideration
was also given as to whether the synaptic contacts were all dyadic (with the consequent
ambiguities in the identification of the functional postsynaptic partners) and whether they were
DESCRIPTION OF FIGURE 21 (OVERLEAF)
FIGURE 21. Circuit diagrams of nervous system. Diagrams show the pattern of connections made via gap junctions
(T) and via chemical synapses (arrows) between classes of neuron. Sensory neuron classes are represented by
triangles, interneurons by hexagons and motoneurons by circles. Chemical synaptic connections are graded
according to their prominence on a scale of I to 4 (cross-hatches on arrows). Most neuron classes have been
included in the diagrams; some have been included in more than one diagram for clarity.
44 J.G. WHITE AND OTHERS
P H ,LY '~,,
x
(( > 7 xx
'~ ~ ---q U Rx rIR. RIH,HsN RIM
KIourE gl. (a) Circuitry associated with amphids.
". ~ SAB '~ BA~r:: ~,m ash HDC-,~.._ "
D ' ASn ' B
urx s
LUA DVA
/ T urx /
! / &.z , , /,,~
IIV DBn
SMD/ P D
,L2 C E SMB //
AVD~ /13
VAn ADL RID URX
ue)u..~l__~
FIGURE. 21. (b) Circuitry associated with other sensory receptors in the head.
THE MIND OF A WORM 45
f~ ~ :'v~
/ J ...........
i 1 '~
SH i OCt
2[X ^o~
......
M ---'-
! ~'~AV E
~ , ~ ~v~ ~.__5~ ~v^
~ ^~ ....
FIGURE 21. (c) Circuitry associated with the motoneurons in the nerve ring.
PVR
I RIR
AQR
SMa
--""'~: ^ ~z
>~ ~ DVA ~u~
AVM Alu Al Z
.... ~v ....
PVP URX PHC
SDQ /N PLM
D pPHA
VD
AVJ
r,~w
~vJ
QR
~ / S^A AOL P"B
PHC
FLP RI B VAI2
SD
PVM
AUA PHB~
ASH /PQR
/ t u~o
/ t SDQ
P VB
ADC
AQR
PQR
RIM ~. LUA
LP~ PLM
ElS RIG
BAG RMG
AVJ
NMJ
FIGURE 21. (d) Circuitry associated with the motoneurons of the ventral cord.
46 J.G. WHITE AND OTHERS
NMJ(VC) ASH
AVA ADL
AVL FLP
VDn
SAB
VAn
DA9
HDC
BDU
AVG
AVl]
RIG
AVH
HDC
AVH
VDn
ALM PV
AVM
RIM AVH
An
DAn
DA9
AIZ
SDQ
~v~
AQR
SMB
^IZ
^UA
DBn
VBn
VDI2 AVl
FIGURE 21. (e) Circuitry associated with neurons in the tail ganglia.
N MJ (Vulval) P L M
NMJ
(Vulval}
AW
B
^,~~. ,,.-.x~o~.vo.
nMJ(VC}
hi
^DE
~ B~
A AIM
Pv?
AV
RlS l
RlS ~ f'""'--
PVC
J AVB B~G
RIG
.L
ADF
DVA
A
URX
AVG ~' ~"
VD^
AVB
RIM
SMD
RIP
FIGURE 21. (f) Egg-laying circuitry.
THE MIND OF AWORM 47
present on symmetrical analogues, or corresponding cells in another animal. In the case of gap
junctions, the main criteria were the area of contact and darkness of staining of the structures,
and again whether they were present between analogous partners in the same or in other
animals.
Triangular patterns of connectivity
One of the striking features of the connectivity diagrams is the high incidence of triangular
connections linking three classes. These structures may occur frequently as a consequence of
the organization of the neuropile. A typical neuron in C. elegans is accessible (i.e. adjacent) to
a fairly limited subset of the total complement of neurons but is fairly highly locally connected
within this subset (White et al. 1983). Thus, if a neuron has synaptic contacts with two partners,
these two partners must be neighbours to the neuron and therefore are likely to be neighbours
themselves. It is therefore quite probable, given the high level of local connectivity, that there
will be a synaptic contact between them, which will close the triangle. The abundance of
triangular connections in the nervous system of C. elegans may thus simply be a consequence of
the high levels of connectivity that are present within neighbourhoods.
Gap junction circuitry
Of the 104 classes of neuron in the main (i.e. non-pharyngeal) nervous system, 92 have gap
junctions. Many of these classes make gap junctions to members of their own class if they are
accessible to them (48 classes form such intraclass junctions). This is in marked contrast to the
chemical synapses, where unambiguous synapses between members of the same class are
extremely rare. Gap junctions are the presumed mediators of electrical coupling between cells,
and so it seems likely that the gap junctions seen between members of a class may act to smooth
discontinuities of electrical activity between adjacent class members. This may be important
for classes such as the ventral cord motoneurons, for example, where marked differences in
activity of adjacent motoneurons may be inimical to the smooth wave propagation required
for locomotion.
Many neurons have a process that terminates at its point of contact with a process from a
neuron of the same class. Most of the neurons of the amphid sensilla behave in this way, as
do the DDn and VDn motoneurons of the ventral cord. In nearly all the cases where this
apparent contact termination of process growth is seen, there is a gap junction at the site of
contact. (The processes of RIF on the dorsal mid-line are the one striking counterexample to
this general rule.) It seems possible that, in these cases, gap junctions may facilitate
intercellular communication of the signals for inhibiting process extension.
Functional classification of neuron classes
The simplest functional groupings of neurons that are usually made are their categorizations
as either receptor neurons, interneurons or motoneurons. We have used symbols to represent
these neuron types in the connectivity graphs of figure 21. Assignment of a particular class to
a group is, however, not straightforward; several neuronal classes have to be assigned to more
than one group, because they appear to combine two or more of these basic functions. We will
go on to discuss some of the characteristics of neurons in each of these three major groupings.
48 J.G. WHITE AND OTHERS
Sensory receptors
The lack of electrophysiological data on any of the neurons of C. elegans makes the
identification of sensory receptors and their associated modalities rather tentative. We have,
however, selected a set of 39 neurons, which, on the basis of morphology and connectivity, are
likely to function as sensory receptors; these have been listed in table 1.
TABLE 1. PUTATIVE SENSORY RECEPTORS
external differentiated
Neuron sensillum access ciliated rootlet ending
ASE amphid + + ú ú
ASG amphid + + ú ú
ASH amphid + +
ASI amphid + + ú
ASJ amphid + + ú ú
ASK amphid + +
ADF amphid + + (dual) ú ú
ADL amphid + + (dual) ú ú
AFD amphid ú + ú +
AWA amphid ú + ú +
AWB amphid ú + +
AWC amphid ú + ú +
PHA phasmid + + ú ú
PHB phasmid + + ú
IL2 inner labial + + ú ú
IL1 inner labial ú + + ú
OLQ outer labial quadrant + +
OLL outer labial lateral + ú -
CEP cephalic ú + ú
ADE anterior deirid ú + ú ú
PDE posterior deirid ú +
BAG ú + ú +
FLP ú ú + ú +
AQR ú ú + ú
PQR ú ú + ú ú
URX ú ú ú +
URY ú +
ALM ú ú ú +
PLM * ú ú ú +
AVM ú +
PVM ú ú +
URA I' ....
URB I' ' ú '
AUA 1' ....
AVG * ....
ALN * ú ú
PLN * ....
PHC * ....
PVR * ú ú ú
ú Neurons that have undifferentiated processes that run into the tailspike.
? Neurons that have undifferentiated processes that run up to the tip of the head.
The component neurons of sensilla are the neurons that are most likely to have a sensory
transduction function (Ward et al. 1975). There are two general types of sensillum: those that
have channels that open to the outside, exposing some or all of the neurons to the external
chemical environment, and those that have no such channel. The former class is generally
THE MIND OF A WORM 4:9
considered to be chemosensory and the latter, mechanosensory in function. The component
neurons of sensilla are all ciliated and some of the presumed mechanoreceptors also have ciliary
rootlets. There are several other classes of neurons that are not components of sensilla but which
we suspect may be sensory transducers; these are also listed in table 1. The factors that have
been taken as being indicative of a possible sensory function are: the presence of a cilium, the
presence of a specialized, morphologically differentiated ending or the presence of a long,
morphologically undifferentiated process that projects into the extremities (the tailspike or the
tip of the head). In addition to these criteria, all the putative receptors should be exclusively
or predominantly presynaptic.
Of the putative receptors listed in table 1, one group has a definitely known modality;
another's is known with a fair degree of confidence. Laser ablation studies have shown that
ALM, PLM, AVM and probably PVM transduce touch, i.e. light mechanical pressure
(Chalfie & Sulston 1981). The amphid sensilla are strongly implicated as being necessary for
the chemotaxis response, as several chemotaxis-defective mutants have aberrant amphidial
neurones (Lewis & Hodgkin 1977).
Interneurons
The interneurons in C. elegans are fairly diverse in their general organization, but some classes
are conspicuous in that they are restricted in the classes of neuron with which they interact.
The interneurons AIA, AIB, AIY and AIZ, for instance, receive synaptic input predominantly
from the neurons of the amphid sensilla (figure 21 a), whereas RIC receives its synaptic input
from putative mechanoreceptors (figure 21b). Other interneurons do not show such a
restriction in sensory modalities and receive synaptic input from many sources (see, for
example, AVA).
The only other striking grouping that is seen in interneurones is of the classes whose synaptic
outputs are directed primarily to motoneurons. These classes are AVA, AVB, AVD, AVE and
PVC, which synapse onto motoneurons in the ventral cord, and RIA, which synapses onto
motoneurons in the nerve ring. These interneuron classes are among the most prominent
neurons in the whole nervous system. They generally have larger-diameter processes than other
neurons and have many synaptic connections.
Motoneurons
Each of the motoneurons in C. elegans innervates a specific group of muscle cells. This is
particularly noticeable in the head region, where there is a fairly precise mapping of
motoneurons onto their target muscles. Body-wall muscles are innervated by motoneurons in
both the nerve ring and ventral cord. Each of these regions of neuropile contains its own unique
set of motoneuron classes. The body-wall muscles can be logically divided into three regions
according to the source of innervation: the head region, which receives innervation from
motoneurons in the nerve ring, the neck region, which is dually innervated by motoneurons
of the nerve ring and ventral cord, and the rest of the body region, which is innervated by
motoneurons of the ventral cord (figure 10).
Each member of a motoneuron class in the nerve ring generally innervates muscle cells in
two adjacent rows (table 2). Motoneuron classes with fourfold symmetry innervate all eight
rows of muscle with no overlap, whereas motoneurons with sixfold symmetry have fields of
innervation that overlap with each other by one row on each side but not across the
4 Vol. 3x4. B
50 J.G. WHITE AND OTHERS
dorso-ventral mid-line (table 2). Most of the classes of motoneuron with bilateral symmetry
innervate only the lateral four rows; the exception is RIV, which only innervates ventral rows
(table 2).
In addition to the intraclass circumferential mapping shown by the ring motoneurons there
is also some anteroposterior mapping between classes; some motoneuron classes only innervate
head muscles, some only neck muscles, while others innervate both (tables 2 and 3).
TABLE 2. MUSCLES INNERVATED BY MOTONEURONS IN THE NERVE RING
DLM DLL VLL VLM VRM VRL DRL DRM
IL1DL A, B A ......
IL1L ú B, A A .....
IL1VL ú A A ú ú '
IL1VR .... A A ú ú
IL1R ..... A, B A, B ú
IL1DR ...... A A
RIML ..... C C ú
RIMR ú C, D C, D .....
RIVL .... C, D C ú ú
RIVR ú ú C C, D C ' ' '
RMDDL .... A A, B A
RMDL ú B, C ú ' ú A, B, C A, B
RMDVL .... A, C, D A ú ú
RMDVR ú ú A, B A, D C ' ú '
RMDR ú B, C C ....
RMDDR A, B A, B A .....
RMED ú ú A, B, C A, B ú ú
RMEL ..... A, B A, B ú
RMEV A, B, C ...... A, B
RMER A, B A ....
RMFL .... A, B B ú
ú RMFR ........
RMGL ú C C .....
RMGR ú ú ú C, D C ú
RMHL ..... A A, B ú
RMHR ú A, B, C A .....
SMBDL .... A, B, A, B, C
SMBVL ú ú A, B A, B, C ....
S MBVR .... A, B, C A, B ú ú
SMBDR A, B, C B .... B
SMDDL B, C ..... B B, C
SMDVL .... A B
SMDVR ú B B ....
SMDDR B, C C ......
URADL A, B B ......
URAVL ú A A, B ....
URAVR .... A, B A, B ú ú
URADR ..... A, B A
DLM - dorsal left medial, VRL =- ventral right lateral, etc.
ú Branch to NMJ region not present on this cell in NgU animal.
A, B, C, D- sequences of muscle cells in each row, anterior to posterior.
The muscles in the main part of the body are not so precisely mapped by motoneurons as
those in the head. The ventral cord motoneurons either innervate dorsal muscles or ventral
muscles (table 3), there being no finer circumferential divisions. The members of each class
are evenly distributed along the length of the cord and so give rise to a longitudinal mapping
onto the body muscles.
The vulval muscles are innervated by two main classes of motoneuron, VCn and HSN. The
THE MIND OF A WORM 51
TABLE 3. MAJOR MOTONEURON CLASSES
muscles innervated
motoneuron ~ ~ ~ postsynaptic extended processes in
class head neck body vulval anal at NMJs distal processes sub-lateral cords
IL1 + ú ú ú
RIM ú + ......
RIV ú +V .....
RMD + + ú +
RME + + ú ú ú + ú
RMF + ú ú ú
RMG + ú
RMH + .......
SMB + + ú ú ú + +
SMD + + + + +
URA + .......
DAn + *D +D ú ú ú + ú
VAn ú + *V +V ú ú + ú
DBn ú + *D +D ú ú ú -t- ú
VBn + *V + V ú ú +
DDn ú + *D +D ú + ú ú
VDn + *V + V ú ú + ú ú
ASn ú + *D +D .....
HSN ú ú + ú ú
VCn ú + V + ....
DVB + ú + ú
D, dorsal muscles only; V, ventral muscles only; otherwise both.
ú , only the most anterior members of the class make these NMJs.
VCn motoneurons also innervate the ventral body muscles but the HSNs never do this,
synapsing exclusively onto the vulval muscles. The other classes of motoneuron that innervate
ventral body muscles (VAn, VBn and VDn) also have a few synapses onto the vulval muscles
(figure 11), thus the HSNs appear to be the only neurons that are specific for these muscles.
The only motoneuron class that has been seen to synapse onto the set of muscles that mediate
defecation is DVB, but only via a single synapse onto the intestinal muscles. The defecation
muscles are all coupled together via gap junctions, so it is possible that this single synapse from
DVB is the route by which defecation is controlled from the central nervous system. DVB also
makes a few synapses onto body muscles.
Several motoneuron classes have long, apparently undifferentiated processes, distal to the
regions where NMJs are situated, before they eventually terminate (table 3). It has been
-..
suggested in the case of the ventral cord motoneurons VA, DA, VB and DB, that these regions
may function as stretch receptors (L. Byerly and R. L. Russell, personal communication).
These processes will be stretched when the body bends. This arrangement of the stretch-
receptive region adjacent to the NMJ region will therefore result in body curvature's being
transduced into motor activity in an adjacent region. This will mediate the translation of the
region of curvature along the body. The ring motoneurons have processes that run circum-
ferentially around the nerve ring. Two classes of motoneuron in the nerve ring have processes
that leave the nerve ring distally from the region where their NMJs are situated (SMB and
SMD). These processes turn and run longitudinally down the sub-lateral cords. Running in
these locations, these processes are ideally situated to monitor bend in the anterior body, if these
processes have a stretch-transducing function. This would not be the case, however, if they ran
round the nerve ring following on from their proximal regions.
Several classes of motoneuron have processes that are postsynaptic at the NMJs of other
4-2
52 J.G. WHITE AND OTHERS
neuron classes (table 3), and have their NMJs diametrically opposite these postsynaptic
regions. There is nearly always another neuron present, of the same or similar class, which has
the converse arrangement of postsynaptic and presynaptic regions, i.e. it has NMJs where its
partner is postsynaptic and is itself postsynaptic in the diametrically opposite region where its
partner has NMJs (the DDn neurons in the L1 are notable exceptions to this generalization-
White et al. 1978). This reciprocal arrangement of pairs of such neurons suggests that they may
act as reciprocal inhibitors, picking up excitatory synaptic input to muscles from other classes
of neuron and relaying this round to the other side of the animal as an inhibitory input to the
diametrically opposite muscles, ensuring that they work in antiphase. The postsynaptic regions
of these putative cross-inhibitor classes often receive a few synapses from their contralateral
partners (RMD has rather more of these connections than other motoneuron classes of this
type). If these synapses are inhibitory, as is assumed to be the case for the NMJs, then they
could add a certain amount of positive feedback to the system. This would have the effect that
when the other (i.e. non-cross-inhibitor) neuron classes are activated, the system would act as
a bi-stable switch with one side activated and the other inhibited. If the cross-inhibitors have
a time dependent component in their response to stimulation, then the system could oscillate,
one side being activated after the other in succession.
Two classes of motoneuron that have their NMJs in the nerve ring, IL1 and URA, are also
probably sensory receptors. The IL1 neurons are components of the inner labial sensilla; they
may respond to mechanical stimulation at the extreme tip of the head. Presumably such a
simple connection acting directly on to muscles can only mediate a simple withdrawal response.
The function of URA is not clear; it is probably a sensory receptor as it is predominantly
presynaptic in the ring and sends processes to the tip of the head, but the appearance and
disposition of these presumed sensory endings gives no indication as to their sensory modality.
Connectivity
The availability of the complete connectivity data for a nervous system generates an almost
irresistible desire to speculate extensively on the function of such a structure. We will, however,
try to resist this temptation and leave such speculations for future work, when we hope that
they can be backed up by corroborative experimental data. We will, therefore, try to confine
our comments to the general features of the connectivity, some of which may not be obvious
from the connectivity diagrams, and to the functional aspects of those parts of the circuitry
for which there is some relevant experimental data.
Amphids (figure 21 a)
The neurons of the amphid sensilla have synaptic outputs that are predominantly focused
onto four interneurons: AIA, AIB, AIY and AIZ. Most ef the receptors that are situated in
the amphid channel synapse onto the AIA-AIB pair, whereas most of the accessory neurons
that are associated with the amphid sheath cells synapse onto AIY-AIZ. The amphid channel
receptor, ASJ, is unusual in that it alone synapses onto none of the four main amphid associated
interneuron classes, but instead synapses onto PVQ, an interneuron class that has cell bodies
in the tail. PVQ also receives synaptic input from the phasmid receptor neurons, PHA, in the
tail, and synapses onto AIA, thereby providing an indirect route from ASJ onto the major
interneurons.
The interneurons AIA and AIB generally receive a common synaptic input from their
presynaptic partners. These are usually (but not exclusively) mediated by dyadic synapses,
THE MIND OF A WORM 53
with the closely associated processes of AIA and AIB being the postsynaptic elements. There
is generally a bias to AIA, in that receptor neurons often have additional monadic synapses
to AIA or dyadic synapses to AIA with an alternative co-recipient. The main synaptic output
of AIA is onto AIB, and this closes the triangles made by all the neurons that synapse onto
both AIA and AIB. The output from these triangular subcircuits is derived from AIB and is
mainly directed to the nerve ring motoneurons, RIM, and the ventral cord interneurons, AVB.
The interneurons AIY and AIZ do not make as many triangular connections as are seen
on AIA and AIB, although AIY synapses onto AIZ in an analogous way to the synapse from
AIA onto AIB. The main synaptic outputs of both AIY and AIZ are onto RIA interneurons,
which in turn synapse onto the putative cross-inhibitor motoneurons of the nerve ring, RMD
and SMD.
Several of the receptor neurons make direct synaptic contacts with some of the other major
interneurons, thereby bypassing the AIA-AIB-AIY-AIZ system. Most notable of these are the
connections made by ASH and ADF onto RIA and the somewhat less prominent connections
made by ASH and ADL onto the ventral cord interneurons AVA, AVB and AVD.
There are several instances of receptor neurons synapsing directly onto other receptor
neurons. Some of these synapses are quite striking (that of ASE onto AWC, for example) and
some receptors synapse onto more than one other receptor. These receptor-receptor synapses
are not peculiar to the amphid receptors as they are seen between many different classes of
receptor neuron, although the amphid receptors predominantly synapse onto other amphid
receptors. It seems likely that such receptor-receptor connections facilitate the modulation of
the activity of one receptor by another.
Other receptors in the head and their associated interneurons (figure 21 b)
Many of the putative sensory receptors in the head, apart from those of the amphid sensilla,
have connections either directly or indirectly to the five major classes of' ventral cord
interneuron that innervate body muscles (AVA, AVB, AVD, AVE and PVC). OLL and CEP
synapse directly onto AVE; CEP and OLQ. synapse onto RIC, which in turn synapses onto
AVA, for example. There are also connections to the motoneurons in the nerve ring, such as
the direct connections made by OLL onto SMD or the connections made to SMD and SMB
by OLQ and CEP indirectly via RIC. Most of the putative sensory receptors are not exclusively
postsynaptic but receive synaptic input primarily from other sensory receptors; however, these
receptor-receptor connections are not as prominent as receptor-interneuron or receptor-
motoneuron connections. The only receptors with a "Well characterized sensory modality are
the touch receptors ALM, PLM and AVM (Chalfie & Sulston 1981). ALM and AVM have
long, differentiated processes that run in the anterior regions of the body, whereas the processes
of PLM span the posterior regions. Stimulation of the anterior neurons, by gently stroking
animals with a fine hair, causes animals to move backwards; stimulation of the posterior
neurons causes the animals to move forwards. Laser ablation studies have shown that these
responses are primarily mediated by the connections made to AVA, AVD, PVC and AVB
(Chalfie et al. 1984).
Motoneurons in the nerve ring (figure 21 c)
Two prominent motoneuron classes, RMD and SMD, are probable cross-inhibitors in the
nerve ring. RMD receives extensive synaptic input from most of the motoneurons of the ring
(including itself) at dyadic NMJs. Each of the SMD neurons has only one dendritic process
54 J.G. WHITE AND OTHERS
that enters the NMJ region of the ring; this is postsynaptic to RME and the contralateral SMD.
The dorsal and ventral RMEs (RMED and RMEV) have dendritic processes that are
postsynaptic at the NMJs made by SMB. The lateral RMEs have no such processes, however,
and so it is not clear whether this class should be considered to be a cross-inhibitor.
The putative cross-inhibitors of the nerve ring receive extensive synaptic input from
interneurons. This is quite unlike their counterparts in the ventral cord (DDn and VDn),
which are only postsynaptic to ventral cord motoneurons at NMJs. The RIP interneurons,
which provide the only connection between the central nervous system and the pharyngeal
nervous system, have several of the features of cross-inhibitor motoneurons; they are postsynaptic
at the NMJs made by the receptors IL1 and URA, and have axonal processes that cross over
to the contralateral side. It seems likely that they may act to inhibit pharyngeal pumping on
receipt of an appropriate stimulus from IL1, URA or IL2.
The major source of synaptic input to the RMD and SMD cross-inhibitors comes via
extensive synapses from RIA interneurons. These connections are reciprocal; the reverse
connections are quite significant although not as numerous as the forward connections. RIA
is one of the most prominent interneurons in the nerve ring and receives extensive synaptic
input from the RIB interneurons, neurons associated with the amphid sensilla and other
putative sensory receptors with no obvious modality. RIB is also a fairly prominent interneuron,
which makes synaptic connections with diverse partners.
The putative receptors IL1 and URA are both fairly prominent motoneurons in the nerve
ring. They behave as other motoneurons, and make quite extensive NMJs, which are also
presynaptic to cross-inhibitor neurons. They also receive synaptic input from other putative
receptor neurons, notably IL2 and CEP. The IL2 receptors share the same inner labial sensilla
as the IL1 receptors or motoneurons, but unlike the IL1 receptors they are open to the outside
and so are probably chemoreceptive.
The SAA interneurons have long, anteriorly directed, undifferentiated processes that run in
the sub-lateral cords. These processes could possibly act as stretch receptors monitoring the
posture of the tip of the head. The main synaptic output of SAA is directed to the major ring
motoneurons, RIM, and the ventral cord interneurons, AVA. There is synaptic input from the
SMB motoneurons and the VB1 ventral cord motoneurons. Thus SAA interacts with the body
and the head motor systems and, given its possible head-posture transducing function, it seems
likely that these interneurons could function to; couple and coordinate head and body
movements. Such coupling seems to occur during forward locomotion, as there are no
discontinuities between head and body movements in this situation.
Motoneurons of the ventral cord (figure 21 d)
The ventral and dorsal body muscles are innervated by their own sets of motoneurons. Both
sets of motoneurons have cell bodies that reside in the ventral cord (figure 4) and receive their
synaptic inputs from interneurons that have processes that run along the cord. The motoneurons
that innervate dorsal muscles have axons that run in the dorsal cord and join up to their cell
bodies in the ventral cord via circumferential commissures (figure 7).
There are four classes of motoneuron that innervate ventral muscles (VAn, VBn, VDn, and
VCn), and four that innervate dorsal muscles (DAn, DBn, DDn and ASn). Of these, the VAn
and DAn classes are similar and should probably be considered to be the same class, as both
have forward-directed axons and both have the same pattern of synaptic input from
THE MIND OF A WORM 55
interneurons in the cord. In an analogous way, VBn and DBn should probably be considered
as one class, as again both have the same pattern of synaptic input and the same direction of
axon projection, only in this case they are posteriorly directed. All four of these classes have
long, undifferentiated distal regions on their axons, in contrast to the processes of VDn and
DDn motoneurons, which end abruptly at the point of contact with the process of an adjacent
neuron of the same class.
The VDn and DDn motoneurons receive their synaptic input solely from the other
motoneuron classes on one side of the animal, usually at dyadic NMJs, and have their own
NMJs on the opposite side. On the dorsal side, DDn has NMJs and VDn is postsynaptic; on
the ventral side, VDn has NMJs and DDn is postsynaptic. The VDn and DDn could again
be considered as a single class; the disposition of their processes and axons suggests that they
probably are cross-inhibitors. The DDn neurons have been shown to rewire in the course of
larval development (White et al. 1978). In the L1 (first stage) larva their polarity is reversed
from that of the adult, having NMJs on the ventral side and being postsynaptic to DAn and
DBn motoneurons on the dorsal side. The DAn, DBn, SAB and DDn are the only classes of
motoneuron present in the L1 ventral cord; the other classes develop post-embryonically
(Sulston & Horvitz 1977).
The SAB neurons have no synaptic outputs in the adult and L4 larval stages, but in the first
stage (L1) larva the three neurons of this class innervate anterior ventral body muscles (SAB-b).
The only other motoneurons that are seen to innervate ventral body muscles at this stage are
the putative cross-inhibitors DDn. This perhaps suggests that the SAB motoneurons may
provide some excitatory inputs to the ventral body muscles during this stage. In several ways
SAB neurons resemble VAn-DAn neurons. They have the same pattern of synaptic input as
these classes and also have long undifferentiated distal endings to their anteriorly directed
processes. These processes run in the sub-lateral cords, unlike the distal processes of VAn-DAn,
which run ventrally.
The two remaining classes, ASn and VCn, are quite distinct and are less prominent with
respect to their innervation of body muscles than the other classes. The ASn motoneurons
innervate dorsal muscles and are somewhat similar to DAn motoneurons in morphology and
synaptic input. The VCn motoneurons are primarily motoneurons for the vulval muscles
(figure 11), but also innervate ventral body muscles.
There are five main classes of interneuron that provide synaptic input to the motoneurons
of the ventral cord: AVA, AVB, AVD, AVE and PVC. All have cell bodies anteriorly in the
lateral ganglia, except for PVC, which has its cell bodies in the lumbar ganglia in the tail. The
classes AVD and AVE have identical patterns of synaptic output although they have quite
different patterns of synaptic input. The processes of AVE terminate in the mid-body region,
whereas the processes of all the other interneuron classes run the whole length of the ventral
nerve cord. AVA, AVD and AVE make chemical synapses onto the VAn-DAn motoneurons;
AVA also makes gap junctions to them. The dorsal motoneuron class, ASn, has all the classes
of synaptic partner that VAn-DAn motoneurons have, and indeed makes gap junctions with
them, but it receives an additional chemical synapse from AVB.
The VBn-DBn motoneurons are predominantly innervated by gap junctions from AVB and
chemical synapses from PVC together with a few chemical synapses from DVA. Laser ablation
experiments have demonstrated that, in the first stage larva, the DBn motoneurons are
necessary for forward locomotion (backward-propagating body waves), and the DAn moto-
56 J.G. WHITE AND OTHERS
neurons are necessary for backward locomotion (forward-propagating body waves) (Chalfie
et al. 1984). Because of their similar structure and identical patterns of synaptic input, it seems
likely that VAn motoneurons have similar functions to DAn motoneurons, and likewise VBn
motoneurons have similar functions to DBn motoneurons. Considering the sources of synaptic
input to these classes of motoneuron, it seems likely that the AVB-PVC interneurons are used
for forward movement and the AVA-AVD-AVE interneurons are used for backward
movement. There is some evidence for this from laser ablation studies (Chalfie et al. 1984).
Circuitry associated with neurons in the tail (figure 21 e)
The tail region of C. elegans contains a number of classes of receptor neuron, interneuron and
motoneuron that are specific to this region. Most of these neurons project into the neuropile
of the pre-anal ganglion, which is situated at the posterior extremity of the ventral cord. In
general, synapses made by neurons in the tail are smaller and less numerous than those seen
in the nerve ring or anterior ventral cord. Some classes of neuron, such as PVT, PVW and
PDB, make very few synaptic contacts. The major interneurons in the tail circuitry are the
ventral cord neurons, AVA, AVD and PVC, and two interneuron classes with cell bodies in
the tail, DVA and LUA.
The tail has two pairs of sensilla, the phasmids and the posterior deirids. The phasmids are
probably chemosensory, as their component neurons are open to the outside in a similar
arrangement to the neurons of the amphid sensilla. There are two neurons in each sensillum,
PHA and PHB. PHA is unusual; virtually all its synaptic output is directed onto the other
phasmid neuron, PHB. This in turn synapses mainly onto AVA and PVC.
The posterior deirid sensilla are similar in structure to the anterior deirids, and both have
been shown to contain the neurotransmitter dopamine (Sulston et al. 1975). The cell bodies
of the single receptor neuron (PDE) and the accessory cells of the sensilla are situated in the
lateral, mid-posterior regions of the body. The synaptic output of PDE is quite different from
that of the anterior deirid receptor neuron, ADE; its main postsynaptic partner is DVA. The
putative receptor neuron PVM has a cell body in the right-hand posterior lateral ganglion and
has a differentiated ultrastructure that is very similar to that of the anterior touch receptor
neuron, AVM (Chalfie & Sulston 1981). Its synaptic output is quite different from that of
AVM, however, being directed mainly to PDE. This neuron does not seem to be involved in
the touch response (Chalfie et al. 1984) as is AVM.
The posterior body of the hermaphrodite tapers down into a long thin tailspike. Seven classes
of neuron have long, undifferentiated processes that run nearly to the end of this tailspike
(AVG, ALN, PLN, PHC, PVR, PLM and PDB). It seems likely that these neurons are sensory
and that the tailspike is, in fact, a large sense organ, although it does not have the sheath and
socket cells that are components of sensilla. The neurons of the tailspike are quite diverse in
their synaptic connections. PHC has short processes and synapses predominantly onto DVA
and PVC; PVR has a process that traverses the length of the ventral cord and synapses onto
AVB and RIP in the nerve ring. AVG is the only tailspike class that does not have a posteriorly
located cell body; it has a single, rather large cell body in the retrovesicular ganglion. The main
synaptic output of AVG seems to be via extensive gap junctions to the two RIF interneurons
also situated in the retrovesicular ganglion.
The other classes of neuron with processes in the tailspike, ALN, PLN and PLM, probably
have a sensory function in other regions as well as in the tailspike. PLM are the posterior touch
THE MIND OF A WORM 57
neurons and span the whole of the posterior region of the body. ALN and PLN are two classes
that have processes that run alongside, and are closely associated with, the transducing regions
of the processes of ALM and PLM respectively. They project into the nerve ring and it seems
probable that they are also involved with the touch system in some way.
The motoneuron PDB has a proximal process that runs into and out of the tailspike en route
from the ventral to the dorsal cord. No synaptic input is seen onto this neuron; however, it
makes a few NMJs onto dorsal body muscles. It is possible that, in contrast to other
motoneurons with long distal processes, the long proximal process of PDB may have some
transducing function in the tailspike. PDA is another single motoneuron like PDB; both have
cell bodies situated in the pre-anal ganglion. PDA also innervates dorsal muscles but sends its
process to the dorsal cord by a more direct route via a lumbar commissure. It receives some
synaptic input from the interneuron/motoneuron DVB. The only synaptic input to the
defecation muscles is provided by DVB, which therefore (presumably) controls defecation.
PDA may mediate the contractions of the posterior body, which are associated with defecation
(Crofton 1966), via its connection with DVB.
The ventral cord motoneurons, DA8, DA9 and VA12, have rather different patterns of
synaptic connections from the more anterior members of their classes. Although they still retain
the synaptic inputs from AVA and AVD that are characteristic of these classes, DA9, DA8 and
VA12 have several additional sources of synaptic input: VA12 from PHC; DA9 from PHC
and PHB; and DA8 from DVB. In addition VA12 synapses onto DBT, DA8 and DA9. None
of the other VAn motoneurons is seen to synapse convincingly onto other motoneuron classes
except VDn and DDn, and so this feature is probably indicative of an intrinsic difference
between VA12 and the other VAns. The synaptic inputs from PHC and PHB, on the other
hand, may be restricted to the posterior members of the VAn and DAn classes simply because
of the limited extent of the axons of PHB and PHC in the ventral cord. This would not
necessarily require an intrinsic difference in DA8, DA9 and VA12 compared with the other
members of their class.
The egg-laying circuitry (figure 21f)
The vulval and uterine muscles are predominantly innervated by two classes of motoneuron,
HSN and VCn. The VCn motoneuron class has six members, which are distributed along the
central regions of the ventral cord. They synapse onto ventral body muscles as well as vulval
muscles. The only significant synaptic input that was seen on to them comes from HSN. These
synapses are in close proximity to the NMJs made by the VCns onto the vulval muscles,
suggesting that they could perhaps be mediating a presynaptic inhibition of the VCns. Various
pharmacological agents, including acetylcholine agonists, serotonin analogues and an
octopamine blocking agent, have been shown to stimulate egg laying (Horvitz et al. 1984).
Laser ablation experiments have shown that the HSN neurons are essential for egg laying
(Trent et al. 1983). The circuitry associated with HSN is rather ambiguous. It is predominantly
presynaptic and only receives a few synapses back from its postsynaptic partner, BDU, and
a single synapse from each PLM. This type of behaviour suggests that HSN is not simply a
motoneuron but may have some sensory transduction function that provides the primary signal
for the activation of the vulval muscles. There is, however, no obvious feature of its structure
which suggests such a function.
The same arguments can be applied to the VCn neurons because of their apparent lack of
58 J.G. WHITE AND OTHERS
presynaptic partners, although it is not yet known whether the VCns are essential for egg
laying. Another possibility is that the main inputs for HSN and VCn come via humoral
neurotransmitters rather than by focal synaptic contacts. The sensory integration required to
determine the appropriate moment for egg laying could then be executed in other regions of
the nervous system, with no morphologically distinguishable connections being made to the
vulval muscle motoneurons.
CONCLUSIONS
There are, perhaps, two fundamental questions in the field of neurobiology: how neurons
organize themselves during development into specifically interconnected networks, and how
such a network functions. A knowledge of the detailed structure of a nematode's nervous system
does not in itself provide any answers to these questions, but it does at least provide a framework
within which it is possible to pose rather more specific questions.
The development of a nervous system can be divided into three separate phases. The first
is the generation of a group of differentiated neurons; the second is the outgrowth and guidance
of processes from these neurons and the third is the establishment of connections between
processes. The structural data on the nervous system provides information that is most
pertinent to the last two phases. This is because the final structure represents the ultimate
consequences of the execution of these two processes. We will go on to discuss how these two
developmental processes, together with the question of nervous system function, may be further
explored in C. elegans.
Process placement
One of the most striking features of the nervous system of C. elegans is the precision with which
processes are positioned relative to their neighbours within process bundles. Synaptic contacts
are made en passant between adjacent processes; the set of possible synaptic partners that a
neurone may have is therefore limited to the set of processes that are neighbours. Given the
unbranched nature of nematode neurons, this set is usually a relatively small subset of the total
complement of neurons that make up the nervous system. Within this neighbourhood, however,
neurons are fairly highly connected, making connections to nearly half their neighbours on
average (White et al. 1983). Furthermore, there is circumstantial evidence that this level of
connectivity may be independent of neighbourhood, i.e. that a given neuron may make
synaptic connections to more or less the same percentage of its neighbours no matter what class
they may be (White et al. 1983). Thus process placement must be a major determinant in the
establishment of the patterns of connectivity within the nervous system of C. elegans.
It seems likely that there may be two aspects of process placement: substrate guidance of
pioneering processes to establish process tracts (Berlot & Goodman 1984), and the positioning
of processes relative to their neighbours within bundles once process tracts have become
established. A distinctive feature of the organization of processes within bundles is the close
associations that are seen between specific processes, or between a process and the basal lamina.
Such associations are probably the consequence of selective adhesive affinities between the
associating entities. Given the probable importance of selective adhesivity in determining
connectivity, it is worth considering, within the context of the nematode's nervous system, how
such phenomena may be further investigated.
THE MIND OF A WORM 59
Many behavioural mutants have been isolated in C. elegans; it is likely that most of their
phenotypes are the consequence of alterations in the nervous system. It is also likely that some
of these alterations could take the form of misplaced processes. Up to now, relatively few
behavioural mutants have been analysed at the ultrastructural level. This is mainly because
of the considerable effort that is required to reconstruct a significant portion of the nervous
system from electron micrographs. Recently, staining techniques have been developed that
allow the visualization of specific processes or process bundles in whole mounts of C. elegans
when viewed with the light microscope. In one of these techniques, sensory process tracts are
labelled by dye filling (Hedgecock et al. 1984). In another, processes of certain neuron classes
are labelled with monoclonal antibodies and viewed by immunofluorescence in whole mounts
(Okamoto & Thomson 1984). Such techniques will facilitate the pre-screening of behavioural
mutants for those that have abnormalities in process placement. Selected mutants may then
be subjected to a full ultrastructural analysis.
With the dye uptake technique, certain mutants have been found to have abnormal
projections from sensory receptors (Hedgecock et al. 1984); such mutants could be candidates
for substrate guidance. The defects in these mutants could either be located in the neurons,
or in the substrate upon which they grow. It may be possible to distinguish between these two
possibilities by means of mosaic analysis (Herman 1984).
Of the mutants that have been analysed by serial section reconstruction, one (unc-30) has
been found to have misplaced processes on the VDn and DDn motoneuron classes (J. G. White,
S. Brenner & R. Durbin, unpublished observations). The disposition of the processes of the
other motoneuron classes in the ventral cord appears normal. It seems possible that such a
mutant could be defective in the class-specific expression of an adhesion factor. The molecular
analysis of genes that affect process placement may provide a route to an eventual understanding
of the function and deployment of region-specific adhesion molecules. Another route to the
same end may be taken by directly looking for putative adhesion molecules. Candidate
molecules would be expected to be common to a group of processes that are closely associated
together. Such a molecule could be sought either directly by using antibodies, or indirectly by
looking for species of messenger RNA that show the appropriate neuronal distribution.
Synaptic specificity
Although we have played down the role of synaptic specificity in the generation of the
pattern of connections within the nervous system of C. elegans to a certain extent, it is clear that
there has to be some level of specificity. On average, a neuron is presynaptic to about 15 %
of its neighbours (unpublished observations). The subset of neighbours that are postsynaptic
to a given neuron is fairly constant from animal to animal, and so is presumably actively
selected. It is likely that synaptogenesis is initiated by a cell-cell recognition event. Such an
event may involve the binding of a surface receptor molecule on one cell to a matching 'label'
molecule on another cell. If all cell classes had single distinguishing label and receptor types,
then the set of synaptic partners of a given cell class could never intersect with that of another.
Such intersections are, in fact, the general rule in the nervous system. Therefore, if such a
label-receptor system is the basis of synaptic specificity, then the labels (and/or receptors) have
to be arranged combinatorially.
It is probably not reasonable to assume that the pattern of connections seen between
processes in a particular neighbourhood is solely the consequence of the intrinsic specificities
60 J.G. WHITE AND OTHERS
of the neurons involved. There are suggestions that interactions between synapses may act to
modify certain patterns of synaptic connection that might otherwise form as a consequence of
specific neuron-neuron recognition. There are slight differences in connectivity between the
dorsal and ventral members of the classes SMB, SAA, OLQ and RMD. These differences are
manifested as reciprocal substitutions of gap junctions for chemical synapses and chemical
synapses for gap junctions. This behaviour may suggest that there are interactions between
these types of connection in these circumstances, and that these interactions result in a mutual
exclusivity of chemical synapses and gap junctions.
We have used the criteria of morphology and connectivity to define the 118 classes of neuron
that have been described. Given that a particular neuron can only select synaptic partners from
its neighbourhood, it is probable that there are classes that we have defined that have the same
intrinsic synaptic potential; in other words, if placed in the same neighbourhood they would
select the same subset of neighbours as synaptic partners. Therefore, the number of classes that
we have defined (118) is almost certainly an overestimate of the number of neuron types that
are intrinsically different in their specificities. It is strongly suspected, on the basis of
morphology, that AQR and PQR are members of a single class, as are ALM and PLM, ALN
and PLN, and AVM and PVM. It is probable that there are other class equivalences that are
not so obvious, particularly among the interneurons, which often do not have distinguishably
different morphologies. It may be possible to identify such 'superclasses' by a neighbourhood
analysis. If the neighbourhoods from two classes are compared and common neighbours are
identified, then it is possible that the two classes may be members of a superclass, if the pattern
of synaptic connections made to the common neighbours is the same in each case. By
considering all pairwise combinations of classes, and then reiterating the process considering
all members of putative superclasses as equivalent, it may be possible to arrive at a logically
consistent set of superclasses. These superclasses will define groups of cells that have intrinsically
identical synaptic specificities. Such an endeavour may not just be an idle intellectual exercise,
as a knowledge of such 'supergroups' could facilitate the identification of mutants that have
altered labels or receptors. Such mutations would be expected to have pleiotropic consequences,
affecting all the members of a supergroup. Thus mutants that affect connectivity of all the
members of a particular supergroup are candidates for mutants with altered labels and/or
receptors. An analysis of such mutants may provide a possible route towards an understanding
of the molecular basis of synaptic specificity.
Nervous system function
The relative simplicity of the structure of the nervous system of C. elegans provides a challenge
to determine how it functions. The main disadvantage of this nervous system from the point
of view of functional studies is that the small size of the component neurons precludes the use
of electrophysiological recording techniques. Such techniques can, however, be used with
Ascaris. There are considerable homologies between the ventral cord motoneurons of Ascaris
and C. elegans (Stretton et al. 1978); more recently, similar homologies have been seen in the
interneurons of the retro-vesicular ganglion (Donmoyer, Angstadt and Stretton, personal
communication). The neurotransmitter dopamine has been shown to be present in the same
classes of cells in the two animals (Sulston et al. 1975)- It seems likely that such structural and
biochemical similarities may indicate an underlying functional similarity, justifying the
extrapolation of data obtained from one animal to the other. Electrophysiological studies on
homologous cells in Ascaris suggest that the DAn, DBn, and ASn motoneurons of C. elegans are
THE MIND OF A WORM 61
excitatory, whereas the DDn and VDn motoneurons are inhibitory (Johnson & Stretton 1980).
Further work may yield information about the role of the interneurons of the ventral cord in
activating the motoneurons.
The functional aspects of the nervous system of C. elegans may be studied directly by
characterizing the behavioural consequences of specific lesions in the nervous system. Lesions
may be produced by laser microsurgery (Sulston & White 1980), a technique that is capable
of removing any cell or small group of cells within the nervous system. As an alternative, use
may be made of lesions produced as a consequence of mutations. For example, one mutant,
unc-80, specifically affects the organization of the VDn and DDn motoneurons in the ventral
cord, leaving the other motoneuron classes relatively unaffected (J. G. White, S. Brenner &
R. Durbin, unpublished observations). This mutant is uncoordinated in forward and backward
locomotion. When stimulated by a tap on the head, instead of backing away, these animals
shorten by simultaneously activating both their ventral and their dorsal muscles. This
behaviour is what one would predict if cross-inhibition between the dorsal and ventral sides
were lacking. This observation reinforces the suggestion, originally made on morphological
criteria, that the VDn and DDn classes function as cross-inhibitors.
The combined techniques of laser microsurgery, mutants and tests for drug responsiveness
have been used to produce detailed models for the function of the circuitry associated with the
touch response (Chalfie et al. 1984), and the circuitry that controls egg-laying (Horvitz et al.
1984). Other areas of the nervous system should be equally amenable to such methodologies,
particularly the chemosensory system. This system is particularly attractive, as the chemotactic
response has been characterized (Ward 1973; Dusenbery 1974) and many mutants that are
defective in chemotaxis have been isolated (Dusenbery et al. 1975; Lewis & Hodgkin 1977).
We would like to thank our colleagues who, over the years, have offered advice and
encouragement for this work. We would particularly like to mention Donna Albertson, Martin
Chalfie, Richard Durbin, Edward Hedgecock, Robert Horvitz and John Sulston for the many
stimulating discussions that we have had together, and also Donna Albertson, Leon Nawrocki
and John Sulston for reading and commenting on the manuscript.
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APPENDIX l. CONNECTIVITY DATA
In this section, all the detailed connectivity data for each of the neuron classes are presented.
The neuron classes are arranged in alphabetical order; the data for each class are fairly
self-contained. Some classes have been grouped together because they share many common
features; PLM is listed with ALM, PLN with ALN, PVM with AVM and PQR with AQR.
The data that are presented were derived primarily from three reconstructed animals; the
N2T series, the N2U series and the JSE series. Together these series covered the whole of the
animal except for a region in the posterior body (figure A 1). This region was covered by a
partial reconstruction of a male (N2Y series). Data from this animal provided information on
the neurons of the posterior lateral ganglia and the motoneurons of the posterior ventral cord.
The neuropile of the nerve ring and anterior ventral cord was also reconstructed from an L4
larva (JSH series, figure A 1). These data were mainly used as a check on the N2U
PHARYNX VULVA AN U S
i ú ~ I {
N2T JSE
1
N2U i I
N2Y
JSH
FIGURE A 1. The regions covered by the five separate reconstructions. The NgT, Ngu and JSE series were adult
hermaphrodites, the JSH series was an L4 larva and the N2Y series was an adult male.
64 J.G. WHITE AND OTHERS
reconstructions, which covered this region and are not shown, except in the case of RMF, where
there was a significant difference between the two series.
Neuron topographies are shown in semidiagrammatic form for simplicity in presentation.
Processes of neurons in C. elegans have few, if any, branches and tend to run in parallel process
bundles. It is therefore possible to give a reasonably accurate impression of their three-
dimensional structure by means of such diagrams. Neurons that inhabit the regions of the nerve
ring and anterior ventral cord are plotted out in diagrams on templates of the form shown in
figure A 2. Similarly, neurons that have processes in the posterior ventral cord are plotted out
in diagrams on templates of the form shown in figure A 3. Additional diagrams show the
disposition of the cell bodies and processes of the class members within the animal, as seen from
a lateral viewpoint. The nerve ring or anterior ventral cord diagrams are drawn as if from
a dorsal viewpoint of an animal in which the nerve ring has been flattened so as to lie in the
same plane as the ventral cord. The diagrams of neurons in posterior regions are again drawn
from a dorsal viewpoint, but in this case an imaginary cut has been made along the dorsal
mid-line and the animal opened out fiat so that the ventral mid-line runs along the centre of
the diagrams (figure A 3).
Processes that run in the regions covered by these types of diagram have been drawn out
with all their synaptic connections listed. Synaptic connections mediated by chemical synapses
are depicted by arrows. The direction in which the arrow points relative to the process indicates
'"' iSALBUNDLE SUB-LATERAL
ERVE RING
JUNCTION OF VENTRAL CORD
AND NERVE RING
VENTRAL ~ AMPHIDIAL COMMISSURES
GANGLION
CRETORY DUCT
RETRO- VESICULAR
GANGLION
DEIRID COMMISSURES
FIGURE A 2. Diagram of the projection and template used for the plots of processes that run in the nerve ring and
ventral cord. The nerve ring has been flattened out to lie in the same plane as the ventral cord, so that the
posterior face of the nerve ring and the dorsal face of the ventral cord are directed out of the page. The shaded
region indicates the extent of the neuropile in these regions. The isthmus of the pharynx passes through the
hole in the middle of the nerve ring. The disposition of the major process tracts that join this region of neuropile
are shown.
THE MIND OF A WORM 65
PRE--ANAL DORSO- RECTAL
GANGLION ~GANGLION
~1TAILSPIKE I
__/ ......
DORSAL CORD / LUMBAR GANGLION
LUMBAR COMMISSURES
FIGURE A 3. Diagram of the projection and template that is used for the plots of processes in the tail region. This
is a dorsal view of the projection obtained by making an imaginary cut along the dorsal mid-line and then
opening and flattening the animal. The outlines indicate the dispositions of the process tracts and ganglia. The
rectum passes through the hole in the middle.
whether the process is presynaptic or postsynaptic for that particular contact. Synaptic contacts
in which the process is one of several that are postsynaptic to a single presynaptic element are
marked with an asterisk. All possible postsynaptic partners of contacts in which the process
is presynaptic are shown. Gap junctions only appear between two elements and are marked
with a T; no directionality is implied.
Certain synaptic connections have additional labels. These labels refer to a set of electron
micrographs, which illustrate these connections. Many illustrations were taken from the JSH
series because of the better quality of the pictures that were obtained from this series. Although
the diagrams refer to connections seen in the other series, it was nevertheless possible to use
these illustrations, because in most cases synaptic connections equivalent to those indicated in
the diagrams could be found in the JSH series. References to illustrations of synaptic contacts
are made by an index letter. These refer to the set of illustrations that is associated with the
neuron class currently under discussion. If the index letter is preceded by an asterisk then the
index letter refers to the set of illustrations associated with the class being referenced.
The two diagram formats described above do not cover the central body region, particularly
the region of the ventral cord in which there are many synaptic contacts. Data from this region
are presented in two ways' either as a table of synaptic contacts, in the case of interneurons
which have processes that enter the region, or as individual diagrams, for motoneurons that
are totally contained within the region. The motoneurons of the ventral cord have up to thirteen
members in each of the classes, compared with a maximum of four members for all the other
neuron classes in the animal. Only one' typical' member of each of the ventral cord motoneuron
classes is plotted, together with any atypical members that there may be in the class.
5 Vol. 3 i4. B
66 ADA
--~ ADAL, ADAR
~i AVBL
AVBR--_ ~ "AVBL, AVJL
AVBL,RIPL --
.......... ..........
/ ~AVBR,AVJL
/ ,, RICR*
~ ~ RMGR*
--- ~ AVBR,AVJL
AVEL, AVJR~------
.... --t -- ~/ --t ....
AIAL* ----~'
AIAR*
ADFL -~ ú AWAL --~ADFR
~ . iI~ASH~, [,** . ú --J"'----AsHRADFR*
PVPL*
AVBR,RIML AVAR, FLPR ~ i /
AIBRL
AVBR, AIBR -,e--- , AVBL, RIMR
AVEL
1
SMDVL ~ ' /
ADAL / ADAR
SMDVL ~ , ,IDVR
)ER* / LATERAL
PVQL ----{ " CELL BODY
AVDR ---~ ,
ADA 67
AVBL Ra AIZR AvBRC VOL
ADAL RIPL ADAL DVA AVDL AVdL OLQVR AVdL
AVBR ADAR
ADAL e
ADA
Members: ADAL, ADAR.
ADA is a set of two interneurons with cell bodies situated laterally at the level of the second
bulb of the pharynx. Processes enter the neuropile of the retro-vesicular ganglion via the deirid
commissures and run anteriorly into the nerve ring. They then run round the nerve ring and
end in a gap junction to their contralateral partners (b). The processes of ADA are rather small
and run near the centre of the neuropile of the ring, adjacent to the processes of AVA, much
of the time. Synaptic endings are generally small and have large dark vesicles (a). The main
synaptic output is to AVB (a, c), with a few synapses also being made to AVJ (c), RIM, SMD
and RIP (a). There are gap junctions to itself (b), AVD (d), PVO. ASH and ADF.
Magnifications: (a-d) x 25500.
5-2
68 ADE
-
RIGL
AVAR
~~ ~ RIGL
CELL BODY ú CELL BODY
AVAR*
mv ml~,,,, I
CILIATED ENDING IN
ClLIATED ENDING IN
--~ AV KR
DEIRID SENSILLUM
DEIRID SENSILLUM
ú ~ FLPL*
c
ú RMGR
BDUL ú --AVM*
RMGL
ú --AVM
ADE 69
:4t
RI" L DE C AVFL ADEL d
IL2L
.
ADEL
ADE
Members: ADEL, ADER.
ADE is a set of two ciliated neurons with endings in the deirid sensilla, which are situated
in the alae on the lateral lines. The cell bodies of ADE are part of a small group of cells situated
laterally behind the second bulb of the pharynx. Processes enter the retro-vesicular ganglion
via the deirid commissures and then run anteriorly in the ventral ganglion (e). Here they cross
over to the contralateral side and run posteriorly a for a short distance before ending.
the synaptic output is situated in this region and is predominantly to RIG (a) and RIG in
association with AVA (b) although there is usually a bias towards RIG in these dyadic
synapses. The process to the ciliated ending has a branch, which enters the ring neuropile
laterally, running anteriorly through the ring neuropile and making some rather small synapses
to diverse partners; OLL, RMD (c), CEP and FLP are the most prominent synaptic partners
in this region. ADE receives some synaptic input from BDU (*b), FLP (*c), AVM(*) and
IL2L/R. It has gap junctions to AVK (d) in the neuropile of the ventral ganglion. ADE
neurons have been shown to contain dopamine (Sulston et al. 1975)-
Magnifications' (a, c, d) x 25500, (b) x 12750.
7O ADF
i DUAL CILIATED ENDING DUAL CILIATED ENDING
IN AMPHID SENSILLUM' ENSILLUM
'N
/
/
/ \
/ ~ PV PR *
^WBL*---~ ----/'/ \ \
A I glo._.___
.... ....
OLQVL -4---- ----~ ~ -- ~ AWBR
AWBL*------~
RIAL,AUAL ~ ~ ~ [
a ......... --~XI / ........... --- AWL*
AWBL*.___.~ ~ N /
._q
RIH
RIAL ~ --------~ /
RIAL,SMBVL ~ ~\ / -- ~IGR
AWBL* ~
.......... f5›'\
~ RIAR,AIZR
.... I:1 ......
ADAL --q Ill -~ ADAR
RIAL, ADAL ~ I~ ~ RIAR, ADAR
i i
ASHL* -----~ I.~ -.,--- ASHR*
R IAL'.AYZL ~ ~:~ ~ RIAL ~ R IA R, ASHR
ASHL* Z---~ I;I ......
RIAL,AIZL.4----- ~1 ~-- AWBR*
LI
--~ R IAR, SMBDL
AWAR*
-j AIAR
AWAR
ADFL ADFR
CELL BODY IN C LL BODY IN
LATERAL GANGLION
LATERAL
GANGLION
ADF 71
1
ADFL RIAR SMBVL RIAL ,.,, RIAR AWBR
IH AIZL ASHL AD 'R ADFL RIH ADFR AWAR
ADFL (~
ADF
Members' ADFL, ADFR.
ADF is a set of two neurons that have dual ciliated endings in the amphid sensillum. The
endings are in the amphid channel, which is open to the outside (figure 1). Processes from
lateral cell bodies enter the ventral cord via the amphidial commissures and.turn anteriorly
to enter the nerve ring. The processes of ADF run near the outside surface and posterior face
of the ring, in close association with those of AIZ. They meet at the dorsal mid-line and
terminate; there is a gap junction at the point of contact (b). The main synaptic output is to
RIA and AIZ (a); there are also synapses to SMB (c), AUA and RIR, usually in dyadic
combinations with RIA or AIZ. AWB synapses onto ADF in several places (d, *a) and there
are gap junctions to RIH, ADA and AIA.
Magnifications' (a) x25500, (b)-(d) x 12750.
72 ADL
DUAL CILIATED ENDING IN
DUAL CILIATED ENDING IN
"~ "/~ AMPHID SENSILLUM ~ ~
-~ ADLR, ADLL
AIAR,AWC BR
/ ..... / x .......... x
\ x ..........
/ AIBL.~--. ~\ ~ I ~ ----~ASHR
/ AVBL,AVJR-.,~----- ~\ f (~ ----~AIBR,ASER
AVAIl, ~B~ ~ :~.\ ~ v, t.-~-- ..........
/ AIBL ~\
sDQi,*~---~-~'--f~.X v /./-----t oLov.
]_~/------~ ~ AVAR, PVCL
/ AVBL~,----- ~_m\ /7----- ~ AVBR
OLQVL --4
OLQ .....LpLQV L.~L-~-~ ~ / ~ ..........
/~----- ~ AVBR
AVDR'AVJR'4---- ------~ /eTL~ ~ AVDL,AIBR
A IBL, AVDR-~-- ------~_~
1i CEPVL*-----.~ ~\ /o7~ ---,.- AVDL
..... __~,, /7-- .... ~
AVAL. SMDDL ~ ----------~\
AVAR,ASHL ~ ~ ~ { t"'J J
AWBL ~ ~ \
_/e--/~ ~ ASHR,AIBR /
/7--- .... ~
AVAR, .... ~%/ ~~ /
---~A IAR ,AIBR
AVAR ,AVDR ~ /,'~/.~xx ~- ----~A IAR, A I BR //
~D [_L_ ~ ~ / ~D[_~
CELL BODY IN 1 ~ CELL BODY IN
LATERAL GANGLION
LATERAL GANGLION
ADL 73
ALA AVFR j ADLL AVAR
PVQR ASKR ADLL ADLR ADLR / AIBR AVDR
ASER
ADLL (~
ADL
ú Members: ADLL, ADLR.
ADL is a set of two neurons that have dual ciliated endings in the amphid sensillum. The
endings are in the amphid channel, which is open to the outside (figure 1). Cell bodies are
situated in the dorsal regions of the lateral ganglia and have processes that enter the nerve ring
laterally, unlike the other amphid neurons, which enter the ventral cord via the amphidial
commissures. The processes split as they enter the nerve ring and one process runs dorsally
round to the mid-line on the posterior face of the nerve ring, where it meets its contralateral
partner and terminates with a gap junction (b). The other process runs ventrally and
eventually peters out in the ventral ganglion. The general disposition of the processes in the
nerve ring is much like those of the other amphid neurons (such as ASK, alongside which it
runs for much of its length) yet the route from the cell body is completely different. The
processes are large; they run in close association with those of AIB and are filled with vesicles,
many of which are dark-cored (a). The processes are predominantly presynaptic, synapsing
mainly onto AIA (a) and AIB (c) and to a lesser extent onto AVD, AVB and AVA (d). There
are gap junctions to OLO and RMG.
Magnifications: (a) x 25500, (b-d) x 12750.
74 AFD
CILIATED ENDING
................. ~~ ..............
IN AMPHID SENSlLLUM
...... N T"7
/+-'
AWAL* X ~ /~ AIYR
) =
AWAR*
AIYL AIYR
.... ~ ~:i:L
A I YL-~---- --
AINR ~-
AINR ~-
/ ~ AINL
AINR* ~ ~ AWAR*
ASER* ~ ~
ak~
AWAL* ~
AIYL ~ -- ~ ~ AIYR
ASER ~ J'
/
AWAL* ~ ~ ~ AINL*
/~ ~ AIYR
AIYL -.,---- -- ~ AINL*
AWAL ~ ~ /~e --~ AIYR
AWAL* ~ / /~ ~ AWAR*
~.~ ~ AIYR
AWAR
AIYR
AIYL
AIBL --]
AFDL AFDR
CELL BODY IN CELL BODY IN
LATERAL GANGLION LATERAL
GANGLION
0
AFD 75
~ ~J," ~ '~ "' 5;~)~'~~ ~:~~,~.~ ~ ,~. .... ~, .... ~ .......... ..~~:~.~ ~ ~"'~
i
AFDR AIYR a A AWCL ADF
ASER ASEL AIYR AIBL AIYL AIYL AWAL
AIYL AINL ASER ASEL AFDL
AFDL (~
AFD
Members' AFDL, AFDR.
AFD is a set of two ciliated neurons that are part of the amphid sensillum. The endings of
AFD have numerous villi, which poke into the amphid sheath cells (figure 1). The cell bodies
are situated in the lateral ganglia; processes enter the ventral cord via the amphidial
commissures and turn anteriorly to enter the nerve ring. They run round on the outside surface
and the posterior face of the nerve ring in close association with the processes of AIY until they
meet at the dorsal mid-line, where they terminate. There is a gap junction at the point of
contact (b). The only synaptic output is to AIY (a); some dark-cored vesicles are seen in
presynaptic terminals (a). There are synaptic inputs from AIN (c) and AWA (d) and small
gap junctions to AIB in the ventral ganglion.
Magnifications' (a) x25500, (b-d) x 12750.
76 AIA
ASGR
ASGL <
..... ;i~, ........ \ ~ .................
AIA 77
-~?~' '~'.~ .~. .... .- ?~-'~ ...... '~'~ iI .... ~ '.~r r""~' ~,'~?~.,,~,~ ........ ......... 'i
ú ~,..?{~fii~
RIAL /
AIAL AWOL AIBL RIAFI AIAL FIIFL \ AWAL AWBL
A$1L
RIAL
A[A
Members: AIAL, AIAR.
AIA is a set of two interneurons with cell bodies situated in the ventral ganglion. Their
processes run up the ventral cord, run round the nerve ring close to the posterior face of the
neuropile and terminate at the dorsal mid-line with a gap junction to their contralateral
partners (b). The processes of AIA run in close association with the proximal regions of the
processes from AIB (a). AIA is one of the main classes of integrating neuron for the neurons
of the amphid sensilla, receiving synaptic inputs predominantly from ASK (*a), ASG (*a),
ASH (*a), ADL (*a), PVQ (*a-*d), AIM (*a), ASE (*b), AWC (*c), AIZ and ASI (*a).
Most of these synapses are dyadic; AIB is the corecipient. The main synaptic output is to AIB,
often as a dyadic with RIF (a) or AWC (b) as the corecipient. AIA has gap junctions to ASI
(c), AWA (d) and ADF.
Magnifications: (a, d) x 25500, (b, c) x 12750.
78 AIB
AIAL ~ L
ASKL
AS H L * ---------~
AS
/ ^s~R --. )
A SKL* ----~.
....... \ k/ ...... \
~_~ ~k-~ .... /
A IZL ---__~. ~ RIMR
, ...... \7 /
[ ASEL* ~
[ ..... ...___~ _ ~ .... [
I ASEL -----~ _
, ..... //_ .... /
A IAL__._~
_ / ~--- -..--~ R IMR I
/~--- ~ [(I;R ...... /
.......... "J ~ 7- .... /
R IMR*--__~ / / /
.... A .... \ // /
~ ~ ~ DVC*
.......... -,~~-~i~v~ .... /
F I~ ~ '~------fiIZR /
AIAL* . ~ ~IMR, SMDDR /
/ ~ .,~---_...AIZR*' /
...... , t~ ~~: .... /
ASGL* I ~ .~-----.~AIZR /
..... ~ I' ~- .... /
SDQR* ..................._~
DVB ---t 1
ADAL I ---~FLPL, AVAL /
DLL* ú ~ FLPL /
ASHL* ú ~ DVB
FLPL* ----.~ :l --q RIMR,DVC /
#
C -'-~ RIM
ALIBI_
CELL BODY IN
LATERAL GANGLION
c
AIB 79
/ RIBL*- -
RIBL* -- -
AVEL,RIBL -~
DVB,_____~
R IML
RMGL-------~
RIBL
RIML
RIGL ----q
RIBL, AVBR~------ ~ ASGR* [
I
RIBL ,RIML
ASEL *'
AIAR
RIML,AVBR -- -4---------- ASEL
RIGL--~ - ADLR*
RIML,SAADL ~ ~ AIZL ASHR
%
ADLR*
RIML RIMR ~ \ [-~--~! SMDDL AWCR*
k ' -z I I I , ~ ,~ DVC*
k m IDvL~--q~ ~ ~J I-~ IL* ~ ......
....... ~ ~/ [-- DVB / .......
Q~ - ~ ASER*
/
Dvc, --I. I. --t A~,a
RIAL ,AVAR -~---[r /
FLPL* --d' Io - ADAR*
FLPL* ---.ql I
FLPR* --'"~ir [
.......... ---r. !
c AIBR
iii ......
C RAL GANGLION
c
8O AIB
RIBL / AIBR IE AIBL / SAAOL d
i.a
ASER AIAR AIBL AVAL AIBR AVDR RIBL BAGL
AIBL i
AIB
Members: AIBL, AIBR.
AIB is a set of two interneurons with cell bodies situated in the lateral ganglia; it is one of
the main classes of integrating neuron for the receptors of the amphid sensilla. Processes enter
the ventral cord from the cell bodies via the amphid commissures and project anteriorly into
the nerve ring. They then run round the nerve ring close to the posterior face, in close
association with the processes of AIA. When they reach the dorsal midline, at the point where
the processes of AIA terminate, they turn and run anteriorly for about 2.5 !~m at right angles
to the orientation of the neighbouring processes in this region (b). They then turn again and
continue running round the ring, but now in close association with the proximal processes of
RIM near the anterior surface of the ring. They eventually reenter the ventral cord and finally
end in the region of the ventral ganglion. AIB is presynaptic only on these distal regions of
its processes; the predominant postsynaptic partners are RIM (a, c, d), AVB (c), RIB (a, g)
AIB 81
and SAAD (d). Because of the unusual shift of position that occurs on the dorsal mid-line, the
distal and proximal regions of AIB reside in different regions of the ring neuropile and the
synaptic inputs are, therefore, different for these two regions. The proximal regions receive
essentially the same synaptic input as AIA (except for synapses from AIA), with AIB being
the second postsynaptic element in dyadic synapses. Most of the synapses appear to be
symmetrical, although some have a bias towards AIA (e). The main synaptic inputs in these
proximal regions are from AIA (*a, *b), ASE, ADL (*c), ASH, AWC (*b), ASG (*b), AIZ
(*g), ASK (*d) and ASI. The main synaptic inputs on the distal branch are from AIZ
(*e, *f), DVB (*a), DVC (*c), RIM (f), RIB and FLP. AIB has gap junctions to DVB, DVC,
RIG (h), AFD, RIS and RIV (*h).
Magnifications: (a, h) x 25500, (b-g) x 12750.
6 Vol. 3 i4. B
82 AIM
\ ......... ----1 ...........
~,~;~i~i;-~~- -~ ~_ ~.~-A~i~!ii;~ /-
- AIAL,ASGL
~ ......... ~'-'- / 1
..... i ........... \ ............ , ................
GANGLION/ GANGLION
AIM 83
AVDR / MUSCLE j
^l^. I / ^iM. @ ^,M.
AIBR ASGR AIMR ALMR CEPshVL ASGL j CEPDR SIBDL
AIAL
AIML (~
AIM
Members: AIML, AIMR.
AIM is a set of two interneurons with cell bodies in the ventral ganglion behind the excretory
duct. Processes run anteriorly from the cell bodies, adjacent to the lateral surfaces of the ventral
cord. On entering the nerve ring they move round to the inside surface until they reach a
sub-dorsal position, where they loop out into the middle of the neuropile and then return to
the inner surface until the processes meet and terminate with a gap junction on the dorsal
mid-line. The main synaptic output is to AIA, usually in association with ASG (a) or ASK
as dyadic partners. Synapses are also made to AS.] (b), AVF, the cephalic sheath cells (c) and
a few other minor partners. There is not much synaptic input except for a few synapses from
ASK (*c). There are gap junctions to SIBD (d) (there was only one present in the U series
but there is one on each side in the H series).
Magnifications: (a-d) x 25500.
84 AIN
RID
AINR-~
AFDL,ASER
-~ .... -~ ....
AINR--~
AFDR,AUAR
AFDL~
AFDL i -------~BAGL,RIBR
BAGR,RIBL ---------~AFDR
ASER 4
AFDL -- BAGL,RIBR
4 --BAGL,CEPshVR
BAGR,RIBL
AFDL
AFDR
AFDL,ASER
-------~AFDR
ASEL
------~ASEL,AFDR
---~ AUAR
.... _~ ~ ....
ASGR
A IAL, AI BL ~,---- ---~ ASGL
AINL ..... AINR
CELL BODY IN CELL BODY IN
LATERAL GANGLION LATERAL GANGLION
I
c
AIN 85
: ...:.:
i El ^f.R ^u^ INR R
CEPshDL AIYL CEPshVL BAGR CEPshVL BAGR BAGL AINL
ASER RIBL
AINL (~
A[N
Members' AINL, AINR.
AIN is a set of two interneurons with cell bodies situated in the lateral ganglia. Processes
project anteriorly and enter the nerve ring sub-dorsally. They run round the ring to the
contralateral side on the outside surface and then enter the ventral cord, eventually petering
out in the region of the ventral ganglion. The main synaptic output is to AFl) (a, d), BAG
(b), RIB (c), and ASE (a). The cephalic sheath cells may also be receiving synaptic input from
AIN at dyadic synapses (b). AIN has no significant synaptic inputs but has gap junctions with
ASG, AUA (*d) and itself.
Magnifications' (a) x 25500, (b-d) x 12750.
86 AIY
-~AIYL,AIYR
ASEL* ~ I
AWCL* ~ ~ ASER
AFDL
ASEL* ~ ~ AFDR
AWCL*
AFDR*
ASER*
AWCL* --
/
AFDL / ~ AUAR*
r
A WC R *
A I ZL-,~----- ~ A IZR, ADFR
AWCL*
A WCL *-------~
------~ A IZR, HSNL
..........AWcL--AFDL --~ ~ ......'~-----A SG R
A I ZL '4------- C ) -- AFDR
AWCR ~ ~ {
AWCL ~ ~- I
...... ---Y'. ~ ....
.... '---V I ....
-*----- ASEL
ASEL -----~ ~~ ~------A SER
~------ AS E L
'4------- AWCR
...... --i\
AWCL,AWCR ~ ..~'e~ ]~____ ASER -~------ASER*
ASER*------~-~ --i% I .'4-----AWCR*
ASE / /~----AS E R ~-- AFDR
AFDL------~ ~ ~ ~ AWCR*
'//l~---- A~' L ASER*
ASIL*--'''----~ ~._~ ']~ D
AIZL,AWAL~----- f ~,~~ ~------ASER
A S ~ L _..._._..~ _-~ko~ AWCR*
--------~ A IZR, AWAR
AFDR*
ASEL* ~ f ~ -- ~ AFDR
AWC L*------~" /.,~ AWAR*
'~-----AWCR*
mwc~*-----~//
ASEL ------~' /, ~ ASER*
~_./ ......
AWCL ~ ASER*
ASEL ~ AFDR
RIAL, RIBL~-~ ~ AWCR*
~"~----- ASER*
-4----__AFDR
AWAR*
RIAR,RIBR
AIZR
---~RIAR,AIZR,RIBR
ASEL
RIBR
,RIBR
A IY L ~ ..... A IYR
CELL BODY IN VENTRAL
CELL BODY IN VENTRAL
GANGLION
GANGLION
AIY 87
^,zL . ^,~. C .,M. / .I. d
RIBL AIYL/ AIYR BAGR AFDL AIYL
ASHL ASHR
^sGL ^lsL / .WBL .!^~ .U^. .lB. ^,B. ^SG. e
^l^.^Iv. ^lz. AIz. ^,v. ^t^.
AIYL f
AI
Members: AIYL, AIYR.
AIY is a set of two interneurons with cell bodies situated in the ventral ganglion behind the
excretory duct. AIY is one of the main classes of integrating neuron for the receptors of the
amphid sensilla. Processes run up the ventral cord from the cell bodies, forming characteristic
structures in the ventral region of the neuropile of the ventral ganglion (e). The processes then
run round the nerve ring in the posterior region of the neuropile, meeting and terminating at
the dorsal mid-line with a gap junction (b). The main synaptic output from AIY is to AIZ,
RIA and RIB. These synapses are mainly in the region of the ventral ganglion and are usually
dyadic (a) or triadic (e). There are also a few smaller synapses to AIZ laterally in the nerve
ring (c). Synaptic input is predominantly from ASE (*a), AWC (*c), AFD (*a) and AWA
(*c). Gap junctions are made to RIM (d).
Magnifications: (a, d) x 5~5500, (b, c, e) x 12750.
88 AIZ
AIZL,AIZR
-.,---- ADFR
*___~
RI~m
DVA
.~------ RIG R*
OVA
~--_R IBR
~,------ADFR
RIR
AIAR*
RIR*
AWAR-----~ ~ AWBR
ADFR ~ I BR
AIBR,AIAR
AIYR*
.~. AWAR
AWBR*
.~ AWAR*
-- -~----- R I R
AWBR*
~---- R IR
AIBL -,,---- AIYR
SMBDR
* RIR
RIAR~__
R IH*--~
AIBL ,AVEL
SMBVR
ADFR*
.4------ AWAR
~IAR
AWAR*, A I YR*
SMBDR, SMBVR
AIZL
SMBVR
ADFL
ú
AIZL AIZR
CELL BODY IN ~ CELL BODY iN
k.J
LATERAL GANGLION LATERAL GANGLION
AIZ 89
I,-,
vLC
SUBDR RIBLI I R""RU R",
^lZR R,^R ^tZL ^lZR ^,ZL SMBDL R,^L SMBDL
AIZL
?i!
SMDDR e IAR RIGL R g ASHR ASGR
AIBL AIZR ADFR AIZR AIBR AIZL AVBR AIZR
RIML
)
AIZL i
Members: AIZL, AIZR.
AIZ is a set of two interneurons with cell bodies situated in the lateral ganglia. AIZ is one
of the main classes of integrating neuron for the receptors of the amphid sensilla. Processes enter
the ventral cord via the amphid commissures and run anteriorly near the ventral surface of
the neuropile. Most of the synaptic output is in the region of the neuropile of the ventral
ganglion. The processes then enter the nerve ring and run round it in close association with
the processes of ADF near the middle of the neuropile. They move slightly anteriorly on the
dorsal side of the nerve ring and meet and terminate at the dorsal mid-line with a gap junction
between them (b). The main synaptic outputs are to RIA (a, c, d), SMB (a, c, d), AIB (e, f,
g), RIM (e, g), AIY (f) and AVE. The main synaptic inputs are from ADF (*a), AWA (*a),
AIY (*a, *c, *e), RIR (*c), AWB (*a), RIH (*a) and HSN (*f). Gap junctions are made
to ASH and ASG (h) near the amphid commissures.
Magnifications: (a, h) x 25500, (b-g) x 12750.
9O ALA
RID
CELL BODY IN
ADLL* ~ --
DORSAL GANGLION
-- ~ AVER, CE PshVR
AVE L ,CEPshDL~ AVER, RMDR
AVE L ,C E p s h DL-',I--~--
ALA
c
ALA 91
~*?:.~:~*~ i:~!*.~,,:i'~ ',?! ,~...:~:iiii!'~i:~ /~'~'"~~'~~~~' ~ ~~~~~~ii:iS;~ .~-~'
~: ..... ~:.: ~:"~;~?:~.~: !~:/ ~:~-. '~:ii!~~' ...... -~:i~
' i
A.^ / a ^ ,vc. ^.^?
i
CEPshVR SAAVR ALA URXR DORSAL CORD ANAL MUSCLE ALNR
ALA e
ALA f
AI,A
Member: ALA.
ALA is a single cell situated in the dorsal ganglion just behind the nerve ring (b). A short
process enters the dorsal cord and then peters out. Two larger, bilaterally symmetrical processes
leave the cell body and run right and left round the ring, leaving it laterally and running down
the length of the animal, adjacent to the excretory canal and alongside the processes of CAN
and PVD. This group of three processes, which run in close association to the excretory canal,
has not been followed completely along the length of the animal although it has been sampled
in several places. No synapses have been seen from this group except for one small synapse to
the lateral hypodermis (CAN-c). Two of the three processes end at about the level of the anus
and one enters the lumbar ganglion and synapses onto PVC (d). In the nerve ring, ALA has
a few synapses to AVE (a) and possibly CEPsh (a) and a gap junction to RID (c) in the dorsal
cord.
Magnifications: (a, d) x 25500, (b) x 6375, (c) x 12750.
92 ALM AND PLM
ú
N~ RMDDL SIADL
..... ~ h
CEPDL~-------____~7
CEPDL ' --]-I
RMGL* ~ ~ \
BDUL~ ------/4 \
SDQL PVR---{~
---'-'~BDUR
ii
PVCL,CEPVL,AVDR ~ ---~\
UR*
BDUL 4 _ ~mx
pvca,pvcu~---~ 5&\ ---~Pvca
ALML ALMR
LATERAL CELL BODY LATERAL CELL BODY
c
ALM AND PLM 93
. ~"~. -~..~ ..... ~. ~-~~ ~ ........ ...... ~., ...........
BDUR / ADAR a PV~ ALMR CEPDR ALML /
/
ALMR ASHR PVCL j CEPVL MUSI~LE AIMR ADEL BDUL
ALML
^v~, t~v^ e ^v^c i .s., ~[u, co ~,u, h
PDER PLMR PLMR PDER HYPODERMIS PLNR PVCR
ALML PLML j
- ~
' -----~qt
) F"'~ PLM ]
ALM AND PLM
Members' ALML, ALMR; PLML, PLMR.
ALM and PLM are two sets of two sensory neurons that transduce touch stimuli (Chalfie
& Sulston 1981). Both ALM and PLM have long lateral processes, closely apposed to the
94 ALM AND PLM
cuticle, which contain large, darkly staining microtubules (g) (Chalfie & Thomson 1982).
Microtubules with the same appearance are seen in AVM and PVM, which are also part of
the touch-transducing system.
ALM
The cell bodies of ALM are situated laterally in the mid-body (i). Anteriorly directed
processes leave the cell bodies and run near the dorsal edge of the lateral hypodermal ridges
in close association with the processes of ALN (*d). Each process sends off a branch, which
enters the nerve ring sub-dorsally; this then runs ventrally round the ring near the inside
surface, ending soon after it meets a process of AVM. The processes of ALM are predominantly
presynaptic in the nerve ring and synapse onto BDU (a), PVC (b) and CEP (c). There are
gap junctions to AVM (*d)and PVR (d).
PLM
The cell bodies of PLM are situated in the lumbar ganglia (j). Anteriorly and posteriorly
directed processes emanate from the cell bodies and run near the ventral edge of the lateral
hypodermal ridges (g) in close association with the processes of PLN for part of their length.
Gap junctions are made to PVC (h), LUA (*d), and PVR where the processes of PLM cross
the lumbar commissures (j). Each HSN sends out a short ventral branch, which receives a
single synapse from the lateral PLM processes (g). The processes of PLM turn and enter the
ventral cord via a commissure near the vulva. The process of PLML does not get over the
hypodermal ridge (which is rather wide at this point due to the proximity of the vulva) and
has no synapses. The process of PLMR runs along the neuropile of the cord for a short distance
and synapses onto DVA (e), AVA (f), PDE (e) and AVD (e, f).
Magnifications: (a, b, d, g, h) x 25500, (c, e, f) x 12750.
PLM VENTRAL CORD SYNAPSES
synapses to and
partners gap junctions synapses from corecipients
DVA 5PDE
PDE 5DVA
AVA 1, 3AVD, PVC
AVD 1, 3AVA
HSN 2
PVC 2 AVA
LUA 2
PVR g
PHC 1
AVJ 1
ALN AND P LN 95
r SA AV R-.~------
SMBDL, SAAVR
SMBDR, SAAVL
~ ----~ SMBDR
RMGR*
* _...........~ ~)
RIGR ~
SMBVL ! SAADL
SMBVL
SMBVL, SAADL ',,
SMBVR, SAADR
SMBVR
ALNL ALNR
CELL BODY IN
SMBVL, SAADL ~ C E L L B O O Y I N
LUMBAR GANGLION
LUMBAR GANGLION
ELL DY IN CELL BODY IN
~ M G GLION LUMBAR GANGLION ~
96 ALN AND PLN
SMBVR / PLNR V ,.. ALNR ALM!.
LJ
SAADR RMDVL SMDVR SAADL SMDVL AVAL
ALNR ALNR
.._ -- , dI'
i
1 r-'~ ALN 'f
f------~~ ~ ~-
<
~~,:
~ r'""~ PLN g
ALN AND PLN
Members: ALNL, ALNR, PLNL, PLNR.
ALN and PLN are two sets of two neurons with cell bodies situated in the lumbar ganglion
(e, f, g). All four send processes anteriorly, which eventually enter the nerve ring; they also
have posteriorly directed processes that run into the tailspike. The processes of ALN run
laterally and become closely associated with those of ALM in the anterior half of the animal
ALN AND PLN 97
(d). They then enter the nerve ring sub-dorsally and run ventrally round the ring for a short
distance. The processes from PLN are closely associated with those of PLM in the posterior
half of the animal, although the association is not as striking as that of ALN with ALM. The
processes of PLN join the ventral sub-lateral cords in the anterior of the animal and from there
enter the ventral cord via the amphidial commissures. The processes of PLN then enter the
nerve ring and run dorsally for a short distance. The main synaptic outputs of both ALN and
PLN are dyadic synapses to SMB and SAA (a, b) and a few synapses to SMD (c).
Magnifications: (a, b, d) x 25 500, (c) x 12750.
7 Vol. 314. B
98 AQR AND PQR
DVA* ~.
I AVAL, BAG I~_.~ ....
I R!o"-~ --f-- \ lq-- .......... I
I .... .t ,~, (q--~ .... I
.......... _-V. \
\ ......... '--~\ -- /7- .......... /
\ .........~a]
x ...... ::::- ~X '~ // /
\ .... ~---T/ ./›_ ........../
k fF~,~iiil~, /
---q PVPL ..--- PVCR*
X Ii17' / IL
AQR AND PQR 99
:~::~%~i~~':~:;?~i ' i"~' ' ~ '~ ..... ~:2›~ ....... ~ ........
:.:.
AV'BR/ PVCL x a PHARYNX t b ^' c '
AQR / RIAR
AQR AVDR AQR BASAL BODY AVBL i PVCR PVPR BAGL
DVA DVA
f ' h
LUAR ] DB7 AVAIl / PVPL PQR
~'~' t ^v^~ po~ ^v^~ ^v~t PvT ^v^. .v~
RIGR LUAL
AQR i
f g h
r-J j
PQR
7-2
100 AQR AND PQR
AQR AND PQR
Members: AQR, PQR.
Although AQR and PQR have been given different class names, they have several features
in common and so have been grouped together. Each is derived from an equivalent position
on bilaterally symmetrical lineages (Sulston & Horvitz 1977) and each has a small cilium,
which is not part of a sensillum but is free in the body cavity (b). The cell body of AQR is
situated laterally on the right-hand side near the posterior bulb of the pharynx. The cilium
is on a small process emanating from the cell body (i). The cell body of PQR is in the left lumbar
ganglion and its cilium is near the end of a posteriorly directed process (j). The main process
of AQR enters the ventral cord via the right-hand deirid commissure and runs anteriorly. It
splits near the nerve ring and the two branches run round each side of the nerve ring, near
the middle of the ring neuropile and in close association with the process of DVA. The processes
of AQR end without meeting near the dorsal mid-line. The main synaptic output is to AVB
(a, c), AVA (c, e), RIA (d), BAG (d), PVC (a) and AVD. AQR has noticeably denser clusters
of vesicles presynaptically than most of the other classes of neuron. There is some synaptic input
from DVA (*c) and many gap junctions to PVP and also some to AVK (*f) and RIG. PQR
sends an anteriorly directed process that enters the pre-anal ganglion and runs anteriorly in
the ventral region of the process bundle, eventually ending somewhere in the posterior half of
the ventral cord. The main synaptic output of PQR is directed to AVA (f, g) and AVD (g),
usually in dyadic combinations. There are also gap junctions to PVP (h) and there is some
synaptic input from PVN (*c).
Magnifications: (a-c, e, f) x 25500, (d) x 12750, (g, h) x 38250.
PQR VENTRAL CORD SYNAPSES
synapses to and
partners gap junctions synapses from corecipients
AVA l lAVD, 2AVA, LUA
AVD 1 11AVA, AVD, PVN
AVG 1
LUA 1 m AVA
PVN 3 m AVD
PVP 4
ASn 101
AS3 AS3 ASll
AVAR*
AVDL*
>..~---- AVAR*
AVAL*
AVAR*
~ AVAL*
, j ~ AVAR*
"~--"- AVDL*
/ ......
~ ^VAR*
~ AVAL*
~ VA12*
~ NMJ, VD3
I:1 ....
[ ~>---'~ NM J ,VD3
I'l ....
I~>---.~ NM J, VD3
Iff--' VD3, DA3
l ~---~
NMJ, VD3
NMJ VD3
I_,l--'q v^4
^vEa---~ IK--I AVAR
~. ~ ^v~
V' IT-- ^v^~,
›
102 ASn
i!.. -?
I
l
VB3 AVER j AS3 / AS3
!
MUSCLE ARMS AVKL AVAR VA4 VA6 VD4
AS3 COMMISSURE
b d e
^s,, f
ASn
Members: AS1 to AS 11.
ASn is a set of eleven motoneurons, with cell bodies in the ventral cord, which innervate dorsal
muscles. A typical ASn (e.g. AS3 (e)) has rather short processes in the ventral cord on either
side of its cell body. These are exclusively postsynaptic and receive synaptic input from AVB
(*c), AVA (*e) and AVD (*d). In addition AS1 to AS3 receive some synaptic input from AVE
(*f). There are often gap junctions to AVA (c) and VAn (d) in this region also. The anterior
process (except AS11 (f)) leaves the ventral cord and runs round to the dorsal cord as a
commissure (b). All eleven ASn commissures run round the right-hand side of the body. The
process of an ASn turns and runs anteriorly in the dorsal cord, running for part of the time
adjacent to the basal lamina. There are dyadic NMJs in this region with VDn being the
corecipient (a and figure 19). The processes of ASn in the dorsal cord are similar to those of
DAn except that they are shorter and have fewer NMJs.
Magnifications: (a, c, d) x 25500, (b) x 17000.
ASE 103
CILIATED ENDING
IN AMPHID SENSILLUM
104 ASE
IN AMPHID EN ILLUM
....-%
/
/
ASE 105
........... ....... , .....
AIZL ..... x ....
ASER EL A Y L"-'d
AWCR A YL AWGL AIBL
PVQL ASEL
ASEL e
ASE
Members: ASEL, ASER.
ASE is a set of two ciliatcd neurons that are part of the amphid sensilla. The endings are
in the amphid channel, which is open to the outside (figure 1). Cell bodies are situated in the
lateral ganglia and have processes which enter the ventral cord via the amphidial commissures.
From here they run anteriorly into the nerve ring and then run round it in the posterior regions
of the neuropile, in close association with the processes of AIY. The distal region of each process
runs outside the proximal region of the contralateral process. These two processes sandwich
processes of AIY, which is the most prominent postsynaptic partner (a). Synapses are also
made onto AIA (b), RIA (c) and AIB, usually in association with AWC (d). There are synaptic
inputs from AIN (*a), AWA and ASI.
Magnifications: (a) x 25500, (b-d) x 12750.
106 ASG
CILIATED ENDING CILIATED ENDING
IN AMPHID SENSILLUM ~ ~ tN AMPHID SENSILLUM
AlAR, AIBR
r
AWBR
------~A IAR ,AIBR
-- -----~ A IAR !
AIAL ..------- -- ~ AIAR
AIAL ~- - ~ AIAR*
AIAL 4, -- ~ AIAR
~ -----~AIAR
....... AIBL /~..~ ~~ .....
AIAL,AIBL ~
AIML* ~ ~ CEPVR*
AIAL, ~ ~ b) AIMR*
AIAL, A IBL ~------
i
AINL /
AIML* ~ 4---- AINL
AIAL 4---- ~ AIAR
AIAL ~ ~ AIMR*
AINR --~
ASKL, A INR-~----
AWAL*
AIZL ~~
ASGL ASGR
O
ASG 107
i ' ~ ........... .... ~! .... ............ ~ il'~!i~' ,~,~ .~ .... ....
ASGL e
ASG
Members: ASGL, ASGR.
ASG is a set of two ciliated neurons that are part of the amphid sensilla. The endings are
in the amphid channel, which is open to the outside (figure 1). Cell bodies are situated in the
lateral ganglia and send processes into the ventral cord via the amphidial commissures. The
processes run on the outside surface of the neuropile of the ventral ganglion in close association
with the processes of AIA. They project into the nerve ring a short distance, ending laterally.
Synaptic output is almost exclusively onto AIA (a). Some synapses are also made onto AIB
in association with AIA, but AIB always seems to be the minor partner (b). Some of the vesicles
in the synaptic terminals have dark cores (a). ASG is postsynaptic to AIM in a few places (c)
and has gap junctions with AIZ (d) and AIN.
Magnifications: (a, d) x 25500, (b, c) x 12750.
108 ASH
CILIATED ENDING CILIATED ENDING
IN AM t
NSlLLUM
/ AVBL,AVDL~......_
/ ..... -~// '--AW~ X
/ .... --../7 ..........
I ..... F/ .~--- .....
/ ..... ~I~ I
/ -..-..~AVDL,RMGR,AVER
?/ ~ RMGR
-----~AVAR
-----~AVAR,AVDL
-----~AVAR,AVBR
ADLR
__.-------~AVAR
AVDR~...___/ ------~AVDL
AVAL,AVBL~.___.___ ~-----ADLR*
AV BL,~.._._ __
,RiPL.4.__..___ -----~AIAR
AIBL~_.._~
~---RIFR*
/ ! ~IBR,AVDL
AIBL~..__._/ ~ -----~AIAR,AVDL
HSNR*____~ ~~----~AIAR
ADLL*_____~_--- -,,----ADLR*
AVBL,AVDR~.___.._/ ~ __.~AIBR
ADLL*____..~/ ~___..~AIAR~ASKR---'~AIAR
_.--~AIAR,AIBR
tj
.........ii .....
A IAL~____ ~ ASIR
ADAL
A IAL ~__~ ~ ADAR
AIBL,AIAL~-----~~DFL,RiAL __~ADFR,RIAR
RIML,RIAL .4__._ ~ ADFR*
ADFL,RIAL~____ --~ADFR,RIAR
---~AIAR
AIZR
ASHL ASHR
O CELL BODY IN
ASH 109
/
..a ^s.. ^vB[ ^s.[ / ^vD.
^,Bl ^s~. ^v^~ ^v^. ^v~. ^,^~ ^s.. .,^~
ASHL e
ASH
Members: ASHL, ASHR.
ASH is a set of two ciliated neurons that are part of the amphid sensilla. The endings are
in the amphid channel, which is open to the outside (figure 1). Cell bodies are situated in the
lateral ganglia and send processes into the ventral cord via the amphidial commissures. From
there the two processes pass up into the nerve ring, running near the middle of the neuropile,
and meet and terminate at the dorsal mid-line, where there is a gap junction between them.
Processes from ASH run in close association with those from AIA in the ventral part of the
ring and AVB in the dorsal part of the ring. The main synaptic output is to AIA (a). Synapses
are also made to AIB, RIA (d) and to AVB (b) often in association with AVA and AVD (c).
Some of the vesicles in the synaptic terminals have dark cores (a). There are gap junctions to
AIZ, RIC, ADA and RMG.
Magnifications: (a) x25500, (b-d) x 12750.
110 ASI
CILIATED ENDING
CILIATED ENDING
IN AMPHID SENSILLUM
IN AMPHID SENSILLUM
--~ ASIL,ASIR
A I BL ~------- i
AS ER-,~------- ~
~ '~ - ~ AWCL,AWCR
J J
.~.....__ __
--q ....
AIYL, AWCR''~------- --
AWCL, A IYL ~ --
AWCL ~ ú ~1 AIAR
AIAL~~ ------~ A SHR
AIAL ASKL
A I ZL ' RAI ~ii L~l~
ASIL ASIR
cD
ASI 111
AIAL AIAR / AWOL
ASIR AIAR ASJR ASGR AWCR ASIR ASIL ASKL
AIAR AIAL
ASIL e
ASI
Members: ASIL, ASIR.
AS I is a set of two ciliated neurons that are part of the amphid sensilla. The endings are
in the amphid channel, which is open to the outside (figure 1). Cell bodies are situated in the
lateral ganglia and send processes into the ventral cord via the amphid commissures, which
project anteriorly into the nerve ring. They run round the nerve ring near the outside surface
and meet and terminate at the dorsal mid-line with a gap junction between them (d). The
processes are smaller than those of the other amphid neurons and fewer synapses are seen. The
main synaptic output is to AIA (a) to which they also make gap junctions (b). There are also
some smaller synapses onto AIB, AWC (c) and ASE. Some of the vesicles in the synaptic
terminals have dark cores (a).
Magnifications: (a) x 25500, (b-d) x 12750.
112 ASJ
i ............. ~ ..............
f-~
ASJL AS JR
c
ASJ 113
PVQL ASJL a ASJR ASKR ASKL PVQL
ASKL PVQR ASJL ASJR AIAL ASKL
ASJL (~
ASJ
Members: ASJL, ASJR.
ASJ is a set of two ciliated neurons that are part of the amphid sensilla. The endings are
in the amphid channel, which is open to the outside (figure 1). Cell bodies are situated in the
lateral ganglia and send processes into the ventral cord via the amphid commissures. These
processes run anteriorly near the lateral extremities of the ventral cord and then project into
the nerve ring where they run near the inner surface. At all times the processes of ASJ run
in close association with those of PVQ. onto which they synapse extensively and almost
exclusively (a, b). The processes of ASJ meet and terminate at the dorsal mid-line with a gap
junction between them (c). A few of the vesicles in synapses have dark cores (a) but these are
less prominent than those seen in the other amphidial neurons. Some synapses are made onto
ASK but usually in association with PVQ. (d). There is some synaptic input from AIM (*b).
Magnifications: (a) x 25500, (b-d) x 12750.
8 Vol. 314. B
114 ASK
CILIATED ENDIN ILIATED E
t'"
AIAL,AIML ~ ~ PVQR*
HSNL* --------~ ..,_.. *
AS JR
AIML*
ASJL* A IMR*
---... A IMR, A I A R
-~ A IAR
~-- PVQR*
-~ ASHR
RMGR ~ PVQR, ASKR.
:, ----~ A IAR
ASGL* ~ I'l
..... I/
.....
mt
ASKL ASKR
CELL BODY IN CELL BODY IN
LATERAL GANGLION
LATERAL GANGLION
O
ASK 115
ASKR AWCR a Al ASKR ASGR ASKR AIAR
PVQR AIAR ASKL ASKR AIAR AIMR PVQR AIBR
ASKL e
ASK
Members: ASKL, ASKR.
ASK is a set of two ciliated neurons that are part of the amphid sensilla. The endings are
in the amphid channel, which is open to the outside (figure 1). Cell bodies are situated in the
lateral ganglia and send processes into the ventral cord via the amphid commissures. These
processes run anteriorly near the lateral extremities of the ventral cord and then project into
the nerve ring, where they run near the middle of the neuropile. The processes meet and
terminate at the dorsal mid-line with a gap junction between them (b). Some of the vesicles
in the synaptic terminals of ASK are large and darkly staining (a). The predominant synaptic
output is to AIA (a, b). Some of the AIA synapses also include AIM (c) and AIB (d) as possible
partners. There is some synaptic input from ASJ (*d), PVQ, and AIM. ASK makes gap
junctions with PVQ (a) and RMG.
Magnifications: (a, c, d) x 25500, (b) x 12750.
8-2
116 AUA
URXI~--..~ __
-----~ IA R, R IBR
RI AL,R I BL.~..~ _ ~ RIBR,RIAR
-- ~ RIBR,RIAR
URX L*-----~ --
URXR*
URXR,R{AR
URXL*----~ -- ~----URXR*
, ADFL* ~
__ ___~ RIAR,R IBR
__ ~ URXR*
-4-- ADFR*
__-___~ R IAR, R I BR
ADFL -----~-- ~ RIH*
R IBL*----~ /
..........
---J
AINL
~ ADFR*
AINR-~
, /
O
' '-t AW~R
AUAL AUAR
CELL BODY IN CELL BOOY iN
LATERAL GANGLION LATERAL GANGLION
c
AUA 117
"~i!::;!i~,~...! ~ .... ~:;t:~ ~:-:..,': ~" ..~!~i .!' -~'i. '%?". ú ,. ~
BAGR C.,I A ..
AUAL RIAL BAGL DVA RIAR RMDVR RIBR RMDVR
RIBL AUAR BAGL CEPshVR
AUAL e
AUA
Members: AUAL, AUAR.
AUA is a pair of neurons with cell bodies situated in the lateral ganglia. Anteriorly directed
processes leave the cell bodies and run along with the bundles of processes from the amphid
sensilla until they peter out, with no terminal specializations, just in front of the first bulb of
the pharynx (e). A second process comes out of each cell body and enters the ventral cord via
the amphidial commissures; it then turns and runs anteriorly on the ventral surface of the cord.
The processes of AUA then enter and run round each side of the ring, close to the outside
surface, eventually meeting and terminating in a gap junction on the dorsal mid-line. The main
synaptic output is to RIB (a, b), RIA (a, c), AVE (b) and AVA (c) in various dyadic
combinations. The main synaptic input is from URX (*a) and ADF. There are gap junctions
to URX, AWB and AIN (d).
Magnifications: (a) x 25500, (b-d) x 17000.
118 AVA
--~ A AR ~ RICL*
" SMBDR ,t
/ ........ \
BAGR ~
SAADL*
SAAVL*
-~------- S AAV L
~------- R I MR
SAAVL
,
. /
\ z,r~-- ..... /
/
/
/
X SDQR* ------~ ~/~ ....... /
'~----- A I BL* SAAVL*
FLPR*, SDQL
"'--- DVC* FLPR*
I'l ......
/'/ ......
.... -4:/ ......
/ q'""'---- FLPL
/ ú [""--- FLPL
AVA 119
SAAVR
---[ AVAL X
' / / / ............
SAADR
SAA DR*_____~
SAAVt~ R IMR __~
RICL*
SAA
\
\
\
PVPL* ~ ~----- SDQL*
ADLL*--------~
~ ....... ~vc ~
FLPL*---- .
ú ~ DVC*
PVCR*,ADAL*---~ ~ .4,----FLPL*,DVC*
ADDVCL~ ~ ......
: .~____ A~, / AVAR
~. ...... /
~ c
---q .....
120 AVA
SAADR AVAR / AVAL GLRDL GLRDR ~
\
CEPDL RICR SMBDL
AMPHID RECEPTOR DENDRITES PHARYNX MUSCLE ARMS
~ii~ ' ~-:~:' '"'~~ii~. -' '~'~'~~~::~:~.::: !i:::!ii~ ii ''~!:'~!':'~---~. ...~~ ~'~'"'~'' >'~:'~::!~ ~-:~?~:~:"i ~ii:; :'~ ;i:: i~' '"~:~,~ ..~ '~'~ ?~!~-~: ~: ,~-'~
ffi
VA3 lC VB4 d A~ (~
AVAR VA4 VA5 PVC AVAR ~ AVAL VA2 VA4
PVCL PVCR DA5 AVAR DA3 DA2 AVAR
AVAL f
?
AVAL g
AVA
Members: AVAL, AVAR.
AVA is a pair of interneurons with cell bodies situated in the lateral ganglia adjacent to the
neuropile of the nerve ring. Processes from the cell bodies enter the nerve ring laterally and
run round it, near the outside and posterior faces, to the contralateral side, eventually leaving
the ring ventrally and entering the ventral cord. They then run the length of the cord
positioned near the centre of the process bundle (figure 18), ending near the posterior extremity
AVA 121
of the cord in the pre-anal ganglion. The processes of AVA are rather large and lightly staining
(a); together with those of AVB they are the most prominent interneurons in the ventral cord.
In the nerve ring they are exclusively postsynaptic and receive extensive synaptic input. The
main presynaptic partners in this region are: SAA (*b), FLP (*a), RIC (*a), DVC (*c), PVP
(*c), AUA (*c), ASH (*b), AQR (*c), ADL (*d), SDQ (*b), DVA (*c) and RIB (*g); there
are gap junctions to RIM, URY and itself (a). In the ventral cord AVA is both pre- and
postsynaptic, although the chemical synapses that it makes have rather few vesicles (b, c, d,
e). The main synaptic output is to the ventral cord motoneurons: VAn (c), DAn (d), ASn
(e) and also to PVC (b) and SAB. PVC (*g), VAn (*b), DAn (*c), ASn (*c) and SAB (*c)
have gap junctions with AVA. There is considerable synaptic input from AVD (*a), AVE (*a)
and AVB (*b) distributed along the length of the cord as well as some less extensive input from
PVC (*f), ADE (*b) and PLM (*f). In the pre-anal ganglion, AVA receives synapses from
PHB (*a), PQR (*g) and LUA (*a).
Magnifications: (a-e) x 17000.
AVA VENTRAL CORD SYNAPSES
partners gap junctions synapses from synapses to and corecipients
PVC 10 3 + 11 m 7, 5LUA, 4PVC, 4DAB, 2PDE, VA10, DB5,
VA4, DB3, DA7, DA5
VAIl 8 6ASll, 3DAB, 2DA9, VA12, VA10, VD13
DA8 1 4PVC, 3VAll, gASll, VAI2, DAT, DA9, VA10, VD13
DA4 5 3, 4DA3, 2DA5, 2VA3, VA4
VA10 2 l, 3AS10, 2DA7, PVC, VAll, ASll, DA8
DA5 5 2, 3VA5, 2DA4, PVC, DA6
DA3 2 2, 4DA4, 2DA2, VA3
ASll 6VAll, 2DA8, VA10
DA7 2 2AVA, 2VA10, AS10, DA8, PVC
VA5 6 3DA5, VA6, AS6, DA6
LUA 1 + 19 m 5PVC
DA9 2, 2VAll, DA8
AS5 .2 3VA6, AVB
DA1 8 2, AVA, SABD
AS10 1 3VA10, DA7
VA4 3 PVC, DA4, AS4, DB3
DA2 3 l, 2DA3, AVE
VA6 5 3AS5, VA5
VA3 3 1, 2DA4, DA3
AVE 8 + 30 m 2AS3, AS 1, DA2
AVA 4 3 m 2DA7, DA1 '..:
VA2 3 1, 2AS2
AS2 1, 2VA2
AVD 7 + 56 m SABV, AS6
DB5 2 1, PVC
VA12 1 DA8, VA11
SABV 4 l, AVD
AS6 2 VA5, AVD
AS4 l, VA4
VD 13 2 m DA8, VA11
DB3 PVC, VA4
DA6 DA5, VA5
PDE 2 PVC
AVB 21 + 6 m 1, AS5
AS3 3 2AVE
SABD 4 DA1
AS1 4 AVE
122 AVA
AVA VENTRAL CORD SYNAPSES (cont.)
partners gap junctions synapses from synapses to and corecipients
PHB 21 m
PQR 5+ 14 m
FLP 3 + 14 m
PLM 1 + 4 m
PVN 2 + 4 m
AVJ 2 2m --
PVD 3 m
VDll 2
AVG 1 + 1 m --
VA7 5 --
VA1 2
VA5 1
DA2 1
VA8 1
BDU 2 m
AVB 123
PVC L ~ ~ PVR
pvpL____ ~ [ ------R~rR*
I ,J // //~/ '4------PVCR X
...... / ~ -O<. .... \
UR B[.--------~
AVJR*------~
PVPL* ~
ADAL*------~
ASHL ~ -~
A DAL *-------.-~
ADLL* ~,
ADAL ~ ~ "0
ASHL*-------~ ~ ~ AIBL*
PVCR* ~
ADLL* ~
SDQR ~
ASHL*------~
ADLL* ~ ------
ASHL* ~
SDQR ~
R I FL*-------~
PVR*------~ /
RIFL* ~ /
SDQR--------~/
AVFL* ~ --------
AVFR*-------~ ~
ASHL* ~ 5/ AV jR, --------~
RIFL* ~ /
PVPL* ~ /
AVM* ---4
RIFL*
...... Iii~- /
RIFL* ~
AVM*,RIML*AvBR ~ [
RIML*
~~ ...... r1-1~ .... ~ /
I~l-~c~' /
RID --'-'{ ~ DVA*
124 AVB
AVB 125
AVBR~I AV.~L t AVAR b VC1 / AVBL C AVBRM
AVBL I AVAR AVBR AVBL AS3 AVBR AVER AVDR
AVAL
.::
ASHL RIFL AVBR RIML VA A VBL / g
AVBL PVCL AVJR RIBL AVBR AVBR / PVPR
AIBR RIMR
AVBL h
AVL
AVB
Members: AVBL, AVBR.
AVB is a pair of interneurons with cell bodies situated in thc lateral ganglia. Processes leave
the cell bodies and enter the ventral cord via the amphidial commissures (h). They then turn,
run anteriorly into the nerve ring and run right round it near the middle of the neuropile, in
close association with the processes of PVC and AVJ. They reenter the ventral nerve cord on
the contralateral side and run along it in the dorsal region of the process bundle (figure 18),
ending in the posterior body before the pre-anal ganglion is reached (i). AVB, together with
AVA, are the most prominent interneurons of the ventral cord. The processes of AVB are large
126 AVB
and lightly staining (e, f, g) and have several short projections emanating from them in thc
nerve ring (e, f). AVB is entirely postsynaptic in thc nerve ring, where it receives many synaptic
inputs. These come mainly from RIF (*b), RIM (*f), AVM (*a), PVC (*b), ASH (*b), PVR
(*a), PVP (*a), SDQ (*a), ADA (*a), AQR (*a), FLP (*b), AIB (*c), AVF (*c), ADL and
URX. There are also gap junctions to RIB (*g), SIBV (*d), DVA (*g), RID (*c), SDQ and
itself (g) in the nerve ring. AVB is predominantly presynaptic in the ventral cord, where it
synapses mainly onto AVA (b), ASn (c) and the hypodermis (HDC) (a) together with a few
small synapses onto AVD (d) and AVE (d). There are gap junctions to all the VBn (*c) and
DBn (*c) motoneurons, usually in the vicinity of their cell bodies. AVB has little synaptic input
in the ventral cord; what there is comes from AVF (*c), PVN (*c) and PVC.
Magnifications: (a, f, g) x 25500, (b-d) x 17000, (e) x 12750.
AVB VENTRAL CORD SYNAPSES
partners gap junctions synapses from synapses to and corecipients
AVA 1 + 1 m 21, 2AVA, DA5, AVD
HDC ~ 6
AVD 1 AVA, AVB, AVE
AVE ' 1, AVD, VA4
AS3 2
AVB 1 2 m VD3, AVD
AS10 2
AS4 2
AS6 2
AS5 1
VA10 1
AVL 1
VA7 1
AS1 1
HSN 1
VA4 AVE
VD3 AVB
DA5 AVA
FLP 1 + 5 m
AVG 3 + 1 m
AVF 1 + 3 m
PVN 2 1 + 2 m
PVC 3 m
AVJ 1
AVH 1 m
VC4 1 m
DB3 5
VB7 4
DB7 3
VBll 3
VB4 2
DB5 2
VB8 2
DB1 2
VB5 1
DB4 1
DB2 1
VB1 1
VB3 1
AVD 127
FLPL* i,,
/ ....... -"it' \' /
..... ....[..\ .......
T_~ J/ ....
A DL L * ........_...~ ---------"
-------q ADAL
....... T/ // '~ ....
...... ~l t x'~- 2---A~**
' m .... '~-._X XT--
AS.L , f ..x., ~ ~~ ~ ~ PvcL,
AVDL AVDR
I
AIML* ?
PVPL*--'"* ;'
ADAL----~ ".j /
.-- ~..:
PVCL*
FLPR*
FLPL*
FLPL*
FLPR*
,.~ ., ,.,~.,,
128 AVD
~ -'~i~ili~i:, ::~,~'
~~.~t~ '~
:~::~:'~' ' '/ t^v~'c I ,v=,d
^v^, I ^v j ^v^./ ^v~.
v^~ I ^vo. ^v^, ~v^. o^~ .vc ~s~ ^v^,
AVAR AVAL
.-~ ~'~
,,,/D, / ,,,'~,. / ,,v~, / ,,v~,,.e ,,', ~,,,,v,I, i~,,,,Dg
AVEL RID AIZR AVAR j SABVR AVAL AVDL
!
DA1 SABVL
, fl g
vo. h
f~g d
AVD i
AVD
Members: AVDL, AVDR.
AVD is a pair of interneurons with cell bodies situated in the lateral ganglia. Anteriorly
directed processes leave the cell bodies and enter the ring sub-dorsally, where they initially run
near the inside surface of the neuropile. They move out near the outside surface as the processes
cross over on the dorsal mid-line (e) and move back to the middle of the neuropile as they
carry on round the ring. They then enter the ventral cord where they run near the middle
of the process bundle (figure 18), eventually ending in the pre-anal ganglion. The processes
AVD 129
of AVD are exclusively postsynaptic in the nerve ring and are lightly staining. The main
synaptic input in this region is from ASH (*c), ADL (*d), FLP (*b), PVC (*c) and AQR.
There are gap junctions to ADA (*d) and FLP. AVD is predominantly presynaptic in the
ventral cord having the same post-synaptic partners as AVE. It makes many synapses to AVA
(a, b, c, d) and several to SAB (f, g), VAn (a), DAn (c) and ASn (d), usually in various dyadic
combinations. There are some striking synaptic complexes in the vicinity of the cell bodies of
the SAB neurons, where two presynaptic specializations from AVD and/or AVE (and
sometimes also AVA) occur in the same region with the processes of SAB, DA1 and VA1
sandwiched in between (f). The main synaptic input to AVD in the ventral cord is from PQR
(*g), LUA (*a), PVN (*b) and PLM (*f), there are also minor inputs from AVB (*b), PHB
(*c) and possibly PVW (*c). There are gap junctions to AVJ, AVM (*e) and FLP in the cord.
Magnifications: (a) x 25500, (b-d, f, g) x 17000, (e) x 12750.
AVD VENTRAL CORD SYNAPSES
partners gap junctions synapses from synapses to and corecipients
AVA 2 7, 33AVA, 4SABV, 3DA1, 3LUA, 2DA4, 2ASll,
2SABD, 2AVD, VA6, DA5, PVC, AS4, AS10,
VA5, VAIl, DA8, PQR, VA3, DB4, DA3
DA3 5, AVA
SABV 4AVA, 2SABV
DA4 2, 2AVA
LUA 7 m 3AVA
SABD 1, 2AVA
DA1 3AVA
DA5 2, AVA
VA3 2, AVA
AS 11 2AVA
AVD 2AVA
DA2 , 2
VA6 1, AVA
AS10 1, AVA
PQR 12 m AVA
PVN 6 m
DA8 AVA
PVC 3 m AVA
AS1 1
AS4 AVA
AVB 3 m 1
DA9 1
VA2 1
DVC 1
AS5 1
DB4 AVA
VAll AVA
VA5 AVA
FLP 1 24-18 m
PLM 1 + 4 m
AVJ 4 4 m
PHB 3 m
HSN 3 m
AVG 1
VA4 1
PHA 1 m
PVW 1 m
AVE 1 m
AVM 1
9 Vol. 3 I4. B
130 AVE
'~,::_:~.~,~ii~i' I1-- ......
/ =\ /7-- ......
\ iL::.' o:::' ,
\ _:!!:':-.-:1 /~::.__~::~:~. /
~-----R I BR* /
~' ~ iii:.-I'.1/
:i.'øii,,ilo~ \ ..... :.t/
AVE 131
CELL BODY IN
132 AVE
15:i.15 :Cf
AVAR / AVDR AVEL SABVL DA1 SABVL DA2 AVER
i
AVDL VA1 AVAR
ú ~ ........ ~:i~ii i,~ .... ~~-~~i~?"--~-'"~ ~ ~ .......... ~ ~,~,
~,~iiiii",~:~,~i:,~i~,, ":~ ,~:~,:' ........ ! ~ :~i5~''~'i~:~''''~i~i~! .... Ii ..... ~. .... :',"?" ........ '
~, ~i~ , ~:~.~. :,,,~.
VA3 / AVEL AVA AVER RMEV AVEL
AVAR CEPshVL BAGR
AVEL i
clb/ d al fie
1..
AVE J
AVE
Members: AVEL, AVER.
AVE is a pair of interneurons with cell bodies situated in the lateral ganglion close to the
ring neuropile. Processes from the cell bodies enter the ring laterally and run anteriorly through
the neuropile until they are near the anterior surface. They then turn dorsally and start running
round the ring in close association with the processes of AIB. When the processes of AVE reach
the dorsal mid-line they turn and run anteriorly for a short distance until the anterior surface
AVE 133
is reached, where they turn again and carry on round the ring in close association with the
processes of RIB, until they leave the ring ventrally and enter the ventral cord. They run near
the centre of the nerve cord (figure 18) and eventually end before the vulva is reached (j). The
processes of AVE are exclusively postsynaptic in the nerve ring and are lightly staining in this
region. They receive many synapses, particularly from the mechanosensory system. The main
synaptic input is from OLL (*a), URY (*b), CEP (*d), URX (*b), DVA (*a), RIB (*h),
RIS (*a), BAG (*c) and AUA (*b); there are also a few synapses from FLP (*b), ALA (*a),
AVK (*a), AIZ, RIG, PVC (*a) and RMG. There are gap junctions to RIM (*h), RME
(g) and RMD (h) in the ring. AVE is predominantly presynaptic in the ventral cord and has
the same postsynaptic partners as AVD. It makes many synapses onto AVA (a) and also several
onto SAB (b, c), VAn (c, e), DAn (d) and ASn (f), usually in various dyadic combinations.
There are some striking synaptic complexes in the vicinity of the SAB cell bodies, where both
AVEL and AVER have presynaptic specializations in the same region with processes of SAB,
VA1 and DA1 sandwiched in between (c). There is some synaptic input from AVJ (*d) and
AVB (*d) in the ventral cord.
Magnifications: (a, g, h) x 25500, (b-f) x 17000.
AVE VENTRAL CORD SYNAPSES
partners gap junctions synapses from synapses to and corecipients
AVA 3 m 8, 6DA1, 5DA2, 4SABV, 4AS1, 4AVA, 2DA3,
2AS2, 2DB3, 2VA2, PVC, VA3, DA4, AVD,
1VA4
SABV 4SABD, 4AVA, 4DA1, 3VA1, 2SABV
DA1 6AVA, 4SABV, 2SABD
SABD 4SABV, 2VA1, 2DA1
VA1 3SABV, 2SABD, VA3
VA3 3, AVA, VD3, VA1
DA2 1, 5AVA
AS 1 1, 4AVA
DA3 2, 2AVA
DB3 2AVA
AS2 2AVA
VA2 2AVA
PVC 1 m AVA
DVB VD2
VD2 DVB
VD3 VA3
DA4 AVA
AVD AVA
AS3 1
VA6 1
VA4 AVA
AVJ 2+2 m
AVB 1 + 1 m
AVG 2 m
AVL 1 m
134 AVF.
/ _.J~~-~~~~ .... \
A I M L _......__-.~
/ l/ /i ...... /
\ __. II .if_ ..... /
\ .... ~ .... __~' ~\ W . /
AVF 135
AVBR,HSNR ~ AIMR*
(
/j ...../
I
___~HSNR
---~PVQL PVQR ---'~U /
...... ~ AV F R
AVFL*
c
136 AVF
, .~ ~, :- ~?:: ~i~~-' '.~.~;~,?~,
VC1 LC AVHR DD2
I
AVFR HSNR PVQL PVQR AVBR i AVFR AVFL
AVFR AVBL MUSCLE ARM
-{
AVFL (~
c0
AVF
Members: AVFL, AVFR.
AVF is a pair of interneurons with bipolar cell bodies situated in the retro-vesicular ganglion.
Anteriorly directed processes leave the cell bodies and run together round the left side of the
excretory duct and then enter the nerve ring. They run right round the nerve ring on a
trajectory which is near the inside and posterior surfaces of the neuropile, eventually ending
ventrally. The posteriorly directed processes from the cell bodies of AVF run together in the
dorsal regions of the ventral cord and end in the pre-anal ganglion. The processes of AVFL
and AVFR are at all times closely associated. AVF makes a few rather small synapses, although
in the nerve ring there are several regions that have vesicle-filled varicosities with no associated
synaptic contacts (b). The main synaptic output in the nerve ring is to AVB (a), HSN (a) and
AVJ; the main synaptic input is from AIM and HSN (*c). In the ventral cord there are
chemical synapses to and from AVH (c and *d) as well as several gap junctions. There are
also a few synapses to AVB (c) and several other synapses including a couple of small NMJs
(d) and a few synapses with no obvious postsynaptic partner. There are many rather small
gap junctions between AVFL and AVFR along the length of the cord.
Magnifications: (a) x25500, (b) x 12750, (c, d) x 17000.
AVF 137
AVF VENTRAL CORD SYNAPSES
partners gap junctions synapses from synapses to and corecipients
AVH ' 8 6 m 1, AVL, AVF, AVB, AVJ
AVB 1, AVG, AVJ, AVH
AVF 21 1 + 2 m 1, PVT, AVH
AVJ 1 1 m 1, AVB, AVH
NMJ 2
AVG 1 1, AVB
PVQ. 1 PDE
PDE PVQ.
AVL 1 m AVH
VDll 1
PHA 3 m
VC5 1+1 m
PHB 1 m
VC4 2
138 AVG
-'q VD1
vo ~~~,,~
l"~':v3 F R
RIFL
~ .~----- AVFL
AVG 139
:/.<~d~P ú :: . ! ......
i
G C~ VB1 RIFR VC1 AVG j C V
AVJR I AVER AVG Rl›IR MUSCLE ARMS AVG VC2
AVBL AVFL
b d
~ AVG e
)r-'~ AVG f
AVG
Member: AVG.
AVG is a single interneuron with its cell body situated in the retro-vesicular ganglion. A
posteriorly directed, fairly large process leaves the cell body and runs in the dorsal region of
the cord down to the pre-anal ganglion. Here it runs to the left of the anus and enters the
dorso-rectal ganglion and from there runs down the dorsal hypodermal ridge to the tip of the
tail. The disposition of the posterior extremities of this process suggest that it could be a sensory
dendrite. There are a few scattered synapses in the ventral cord (e.g. d) the most prominent
of which are some synapses to AVB (a). There are several synapses onto the basal lamina
surrounding the nerve cord with no obvious postsynaptic partners (c). The most striking
features of AVG are the gap junctions it makes with RIF in the retro-vesicular ganglion (b).
A short anteriorly directed process from AVG often pokes into the cell bodies of one of the RIF
neurons (b).
Magnifications: (a) x 25500, (b-d) x 17000.
140 AVG
AVG VENTRAL CORD SYNAPSES
partners gap junctions synapses from synapses to and corecipients
AVB 3, AVJ
AVA '~ 1, PVC, HSN
PHA 2 + 6 m PVQ, DA8
AVE AVE
AVF 1 + 1 m 1
VAIl 1
AVD 1
DVB 1
HDC 1
DA8 PHA
PVQ. PHA
PVC AVA
AVJ AVB
AVL PVP
PVP AVL
HSN AVA
PQR 1
RIF 2
PVN 1 rn 1, AVA
AVH 141
,
AVFL
RIFL* ,.
AIML* ~/~ ,
AVJL, AVDL 4 . ~ // ~ AV.JR, ADLR ~
II
RIR 4 --
~ RIFR*
--.--~ AV BR, RIMR
PVPR*
AQR, AVDR
AVHL ' AVHR
PVPL* ----~
BDUR*
PVPR*
IGL
142 AVH
AVAR RIR AQR AVHR d
AVHL AUAR SMBVR ASER AVJL AVHL AVFR AVB
AD "R AWBR VB6
AVHL (~
AVHL f
AVH
Members: AVHL, AVHR.
AVH is a pair of interneurons with cell bodies in the lateral ganglia. Processes from the cell
bodies enter the nerve ring sub-dorsally and cross over to the contralateral side. They then
travel ventrally round the ring, running near the middle of the neuropile, and leave it to enter
the ventral cord. The processes of AVH run in the dorsal regions of the cord and end in the
pre-anal ganglion. The chemical synapses made by AVH are rather small, with few synaptic
vesicles. The main synaptic outputs are to AVJ (c), PVP, SMB (b), ADF (a) and RIR (a)
in the nerve ring. In the ventral cord there are synapses to and from AVF (d, *c) as well as
gap junctions to AVF and also a few synapses from PHA.
Magnifications: (a) x 25500, (b-d) x 17000.
AVH VENTRAL CORD SYNAPSES
partners gap junctions synapses from synapses to and corecipients
AVF 8 3 + 5 m 2AVH, 2AVF, PVQ
PVQ AVF, VD1
AVH 2 m 2AVF
VD1 PVQ
AVJ 1 m AVB
AVB AVJ
PHB
PHA 3 m
PVP 1 m
AVA 1 m
PHC 1 m
VC4 1 m
AVJ 14'3
I/ ..
/ '""----- ADAR*
~_......~V !m
AQR*
AVBR, PVCR
-4- HSNL*
-- AVFR*
HSNR*
a. AVBR,RIFR
ú .~---_ PVNL*
~ BDUR*
-.~-- PVNR*
> -.,--- R I MR*
PVNR*
AVBR
AVJL
I
CELL BODY IN
-.---~ RI S
LATERAL GANGLION ---] RIS
i --.-..~ PVCR, R I S
R I SpVCR
I, II ~
vel.
AVBL, PVCL, PVNR
0
144 AVJ
PvcRPVR* ---"---'~\ /~---'----\ ! PVNL* ~ AVBR, AVJL
/ ~______AV HR*
I ........ -TI I
PvCR, PVCL
.... *PVC--~ ~~ /
AVM, AVBL ~
AVJ 145
/ d
AVJL AVJI-
›
AVJL e
øI
AVJL f
AVJ
Members: AVJL, AVJR.
AVJ is a pair of interneurons with cell bodies in the lateral ganglion. Processes from the cell
bodies enter the ring sub-dorsally and then run round it to the contralateral side near the centre
of the neuropile, in close association with the processes of AVB. The processes of AVJ then leave
the ring ventrally and traverse the length of the ventral cord, running immediately adjacent
and dorsal to the processes of AVB and eventually petering out in the pre-anal ganglion. There
are few synapses from AVJ; and those that are present are rather small and have some
dark-cored vesicles. The main synaptic output is directed to PVC (a), AVB (a) and RIS (b)
in the nerve ring, and to AVE (d) and AVD in the ventral cord. The main synaptic input
is from BDU (*a), AVH (*c), ADA (*c), ADL, PVR (*b), RIF (*b), HSN and PVC in the
nerve ring and PVN (*b) and AVF in the nerve ring and ventral cord. AVJ has a prominent
gap junction with RIS in the neuropile of the ventral ganglion (c); RIS sends a short branch
down into the ncuropile of the cord in this region. There are gap junctions to PVC (*h) in
the nerve ring and to AVD, PVC and itself in the ventral cord.
Magnifications: (a) x 25500, (b-d) x 17000.
1O Vol. 314. B
146 ^vi
AVJ VENTRAL CORD SYNAPSES
partners gap junctions synapses from synapses to and corecipients
AVE 2, 2AVD
AVD 2 2AVE, AVA
AVA AVD, SABV
HSN 1
PVN 2 + 4 m 1
AVB 1
PVQ. 1
AVF 1 + 2 m AVH
AVH 1 m AVF
SABV AVA
LUA 2 m
PVW 1 m
AVG I m
AVJ 4
PVC 2
AVK 147
r
..... ti/ /i' .... /
....... -~\ // /
AQR -~ [ ~ DVC*
AVKL .......... /
c
10-2
148 AVK
7'f o ~l- ..... \
..... -4./ \\ \
..... -PI ~ ....... /
// IT- ..... !
..... T,/ /X
...... Q( /~--~:;:. j
It !~ ..... /
...... ---'tx,iT-- ....... I
' __ \h' 17 ..... I
/
' 'Nx z.-z ......
\ '"'1'1 t/ /
\ ,I,I //, / .2[~R.
\ .... * I!1 I'1 .... ;, / ....
\ .... -Hill II . / .....
\ I1' I/ ',./ ........
Members: AVKL, AVKR.
AVK is a pair of interneurons with cell bodies situated in the ventral ganglion behind the
excretory duct. Anteriorly directed processes leave the cell bodies and run near the centre of
the neuropile. They move ventrally as the nerve ring is approached and then run right round
the ring near the outside surface, emerging on the contralateral side adjacent to the processes
of their partners. At all times, in the regions of overlap, the processes of AVK run in close
association with those of their contralateral partners. The processes travel down the length
of the ventral cord running in the ventral regions of the process bundles on either side of the
150 AVK
hypodermal ridge (c), eventually petering out in the pre-anal ganglion. The main synaptic
output in the nerve ring is on the dorsal side and is directed to RIM (a, b), AVE (a) and SMD
(b). Synapses are received mainly from DVB (*b), RMF (*e) and RIG (*f). AVK has gap
junctions to several partners, namely itself, SMB (e), AQR (f), DVB, PVP (g), RIC, ADE (*d)
and RIG. In the ventral cord there are a few small synapses to hypodermal cells (HDC) (d)
and PDE (c). AVK receives synapses from PDE (*b) and PVM (*f). There are also some rather
marginal gap junctions to PVP.
Magnifications: (a, d, f, g) x 25500, (b, c, e) x 17000.
AVK VENTRAL CORD SYNAPSES
partners gap junctions synapses from synapses to and \
HDC 5, AVM
PDE 1 + 10 m 2, 2PDE
PVM 7 + 4 m 1
DVA 1
PVQ 1 1
AVM HDC
PVP ,5
AVL 151
I
-4--.----
DVB* ~ --
RIS* "
AVL
CELL BODY IN VENTRAL ~ J
Member: AVL.
AVL is a motoneuron/interneuron with its cell body situated in the ventral ganglion. An
anteriorly directed process runs in the mid-line on the dorsal surface of the neuropile of the
ventral ganglion. It enters the ring on the left and makes a complete circuit running near the
outside surface and the anterior face. It then re-enters the neuropile of the ventral ganglion
and runs posteriorly down the length of the ventral cord running in the ventral regions of the
process bundle. AVL has few synaptic connections in the nerve ring. In the ventral cord the
synapses are rather small and are onto muscles (a), SAB (b) and VD12. Synapses are received
from DVB and PVP (*e). There is a gap junction to PVM (d), DVB and several rather
marginal gap junctions to DVC.
Magnifications' (a) 25500, (b-d) x 17000.
AVL 153
AVL VENTRAL CORD SYNAPSES
partners gap junctions synapses from synapses to and corecipients
SABV 4SABD, 2SABV, AVE
NMJ 6
SABD 1, 4SABV
VD12 2DD6, PVW
DD6 2VD12
HSN 1
PVW VD12
AVE SABV
AS1 AVF
AVF AS 1
DA2 1
DD1 1
DVB 1 2 + 3 m
PVP 1 + 3 m
PVN 2 m
VC1 1 m
VC3 1 m
AVB 1
PVC 1
PVQ 1
AVF 1 m
AVG 1 m
DVC 9
PVM 1
154 AVM AND PVM
\ (-b')~.L~l:l ft-:::: ..... /
X ....... i'~1'1 [I ..... /
,.,,.,~
Members' AVM, PVM.
AVM and PVM, although given separate class names, have been grouped together because
of their many common features. Both are known to be touch receptors (Chalfie & Sulston 1981 )
and share with ALM and PLM the large microtubules that are present on the regions of their
processes which are adjacent to the cuticle (Chalfie & Thomson 1982). The cell body of PVM
is situated laterally, on the left-hand side of the posterior half of the body (i). A process from the
cell body enters the ventral cord via a commissure and runs anteriorly along it in an extreme
ventral location adjacent to the cuticle. It terminates in the anterior body after making some
en passant synapses, mainly to AVK (f), PDE (g), PVC (h) and PVR. There are gap junctions
to PDE and AVL (*d). The cell body of AVM is situated laterally, on the right-hand side of
the anterior half of the body (i). A process leaves the cell body and enters the ventral cord
via a commissure, and then runs anteriorly along it in an extreme ventral location, alongside
156 AVM AND PVM
the process of PVM. It terminates at a position just beyond the first bulb of the pharynx. A
branch leaves the main process and enters the neuropile of the ventral ganglion. This splits
and the branches enter the nerve ring at each side, but terminate, while still in the ventral half
of the ring, with gap junctions to the ends of the processes of ALM. Nearly all the synapses
of AVM are on these branches. The main synaptic output is to AVB (a), PVC (a), BDU (b),
ADE (c) and PVR. AVM has gap junctions with ALM (d) and AVD (e).
Magnifications: (a, b, d, e) x 25500, (c, f-h) x 17 000.
AVM VENTRAL CORD SYNAPSES
partners gap junctions synapses from synapses to and corecipients
ADE 1, DA1
DA1 ADE
AVD 1
PVM 1 m
AVK 1 m
PVM VENTRAL CORD SYNAPSES
partners gap junctions synapses from synapses to and corecipients
AVK 1 7, AVM, PVR, PDE, DVA
PDE 2 2 m 3, 5PDE, AVK, PVR
DVA 1, AVK, HDC
PVC 2
PVR PDE, AVK
AVM AVK
HDC DVA
AVL 1
AWA 157
CILIATEO END lNG CILIATED END lNG
AIAR*
ASER, R IFR
ASKR
A I ZR, AFDR
AFDR
~--- ..........
-- ~ AIZR,AFDR
-- ~ AFDR
-- ~ AIZR
AIZL,AWBL ~ __ ~ -- ~ AIZR,A~DR
AIZL,AFDL ~ -- '~ ) -- ~ ASER*
/
_
AIZL
AIZL,AFDL ~ -- ~ AFDR,AIYR
AIYL ~ -- ~ AWBR
-- -----~AFDR
AFDL 4 , -- ~ A F D R
ASEL,AFDL~----- -- ~ AIZR,AIYR
ADAL -..----- t '---~
AIYL
-,~--- A IYA IZL, L* /
AIYL*--~ AIZL .4,----- m
~ArAR ?
ADFR, AWBR
-~ AIZR
'.j
r
AWAL .AWAR
c
Members' AWAL, AWAR.
AWA is a set of two ciliated neurons that are associated with the sheath cells of the amphid
sensilla (figure 1 ). The cell bodies of AWA are situated in the lateral ganglia and send processes
into the ventral cord via the amphid commissures. The processes run anteriorly in the ventral
cord near the ventral surface of the cord and project into the nerve ring, where they run near
the middle of the neuropile. The processes of AWA meet and terminate at the dorsal mid-line
with a gap junction. The predominant synaptic output is to AIZ (a); there are also some
synapses to AFD (b), AIY (c) and ASE usually in dyadic combination with AIZ. A few of
the synaptic vesicles are dark cored (a). There are gap junctions to AIA (d).
Magnifications' (a, d) x 25500, (b, c) x 12750.
AWB 159
CILIATED ENDING
CILIATED ENDING
--{ AWBL, AWBR
A I ZL, A I BR ..,.......--
..,,_..._
/
HSI~ *...._.~
A IZL ..,......_ /' _ ~ ~ ASGR
..... ::::Z:: t .-
___+ __Er.. -- -{ .Mo.
ADLL
RMGL -~
ADFL ~ e-
/
AIZL
ADFL
A I ZL ~ ADFR
'"--- ADFR
AIZL, ADFL.~----
A IZL, ADFL ~ !
ADLL / -- ~ AIZR,ADFR
ADFL, SMBDR
R IA.L, ADFL ~ R IAR, ADFR
-- -,----- AVHL*
R IA L.,~.----- ~ -~RICL
RIAL, ADFL.~--- --
ADFR, SMBVR
AWAR
AUAL -~
AWBL AWBR
c
AWB
Members: AWBL, AWBR.
AWB is a set of two ciliated neurons with flattened, sheet-like endings that are associated
with the sheath cells of the amphid sensilla (figure 1). Cell bodies are situated in the lateral
ganglion and send processes into the ventral cord via the amphid commissures. The processes
run anteriorly in the ventral part of the nerve cord and project into the nerve ring, where they
run near the middle of the neuropile. They meet and stop at the dorsal mid-line with a gap
junction. The processes are fairly small and none of the synapses is very large. The main
synaptic output is to AIZ and ADF, usually together in a dyadic synapse (a). There are also
synapses to RIA (b) and AVB (c). There are gap junctions to RMG (d) and AUA.
Magnifications: (a) x 25500, (b-d) x 12750.
AWC 161
CILIATED ENDING
ASEL*
X ASEL*------~
\ ~::::~~\ _ /
'~ ...... 2 f
,-5 ..... /
~ø.. ~ /
I I Vol. 3 I4. B
162 AWC
CILIATEO ENDING
~ IN AMPHID SENSILLUM
~~~_~ -----_~ A I YR, A IBR
----..~ A I A R
---__~ I AR
ADLR*
------~ IAR
4___ ASIR* 1
A I B L'-t.~. -- .~..~- .4
AIAR*
/
AIYL*-----~- ~ -----~AIYR
-----~A IYR
~k AIYL 4------ __ AIYR
ASIL* -----~
AS IR
AIYR
AIYR,AIBR
, ~ -- ..,,-.-- ASEL
------~A IYR, A IBR
/
AWCR
c
AWC 163
................
ASIL AIYL AIBR AWCL [~ AWCR AIAR U
Il
AWCR
AIAR
AW›~L AFDL AWCR ~,IAR ASEL ASKR AWCL AIBR AWCL
AWCL (~
AWC
Members: AWCL, AWCR.
AWC is a set of two ciliated neurons with large, flattened, sheet-like endings that are
associated with the sheath cells of the amphid sensilla (figure 1). The cell bodies of AWC are
situated in the lateral ganglia and send processes into the ventral cord via the amphid
commissures. These turn anteriorly and run near the lateral surfaces of the cord. They then
enter the nerve ring which they then run right round adjacent to the posterior surface; finally
ending ventrally. The main synaptic output is to AIY (a), AIB (b) and AIA (c) which synapses
back to AWC reciprocally (d). AWC also has some synaptic input from ASE (*d) and ASI
(*c). Occasional dark vesicles are seen at synapses (a).
Magnifications: (a) x 25500, (b-d) x 12750.
11-2
164 BAG
---[BAGR
AVAR
I 2-- .......... I
\ ~ .... ; ,o, /_:/- ....../
//-- .... /
'~ ---lazR /
BAG 165
Members: BAGL, BAGR.
BAG is a set of two neurons with ciliated endings, in the head, with elliptical, closed, sheet-like
processes near the cilium, which envelop a piece of hypodermis (figure 1). These endings have
no associated sheath and socket cells and so are not directly attached to the hypodermis. The
cell bodies are situated anterior to the nerve ring, just ventral of lateral, and send processes
anteriorly to the ciliated endings in the head. Posteriorly directed processes enter the nerve ring
from the cell bodies and then run round the ring to the contralateral side near the outside
surface of the neuropile, eventually ending ventrally. The main synaptic output is to RIA (a,
b), RIB (a, c), AVE (c) and RIG (b). There are a few dark-cored vesicles in the synaptic
terminals (a). There is some synaptic input from AIN (*b), RIG (*d) and AQR (*d). BAG
has gap junctions with itself, RIR (d) and RIG (*h),
Magnifications: (a, b) x 25500, (c, d) x 12750.
BDU 167
ALML
ADE L *-------~ --
ALML
ALML ~ ALMR
PVNL
,~ PVNL
ALMR
__ ..,--____ HSNR*
ALML*
ALMR, SDQR
ALML
ML ~ ~ PVNL
ALMR
ALMR
PVNL*
HSNR ~ AW~
, PVNR
AVM PVNL~HSNR
AVM PVNR*
AVM
AVJR, PVNR .4__ AVM
\
PVNL*
L ~---- PVNR, LATERAL
CELL BODY % ADEL '~'" CELL BODY
AVAL, AVHL
',
Imv~q'l
I ..... ri
168 BDU
'~*~ ~~~:~,, .~::.-.*%-~ i:~
.'i~
AVM ADI ALML PVNL ., HSNL
AVBR AVJL ADEL ADAL BDUL AVJL SAADL RMGL
PVNR BDUL
a
Bou, e
b d
,L
BDUL f
BDU
Members' BDUL and BDUR.
BDU is a set of two interneurons with cell bodies situated laterally in the anterior body (f).
Single processes project anteriorly from each cell body and run adjacent to the excretory canal,
until they enter the retro-vesicular ganglion via deirid commissures. The processes then run.
anteriorly on either side of the ventral hypodermal ridge until the nerve ring is reached. This
they enter, running round near the inside surface of the neuropile in close association with the
processes of PVN, finally meeting and terminating on the dorsal mid-line. The presynaptic
regions of chemical synapses from BDU are generally rather small but have striking, darkly
staining vesicles (a, b, c, d). The main synaptic output of BDU is to AVJ (a), PVN (c), ADE
(b) and HSN (d). The main synaptic inputs are from ALM (*a), AVM (*b), HSN (*d) and
PVN (*a).
Magnifications' (a-d) x 25500.
BDU VENTRAL CORD SYNAPSES
partners gap junctions synapses from synapses to and corecipients
HSN 1, AVA, SAAD
AVA PVC, HSN
PVC 1, AVA
ADE 1
SAAD HSN
Members' CANL, CANR.
CAN is a set of two cells that are closely associated with the excretory canal. The cell bodies
of CAN are situated adjacent and dorsal to the excretory canal at about the level of the vulva
(d). Anteriorly and posteriorly directed processes emanate from the cell bodies and run along
the canal in close association with the processes of ALA and PVD. The anterior process of CAN
ends just behind the nerve ring (d). The three canal-associated processes on each side, ALA,
CAN and PVD, have not been completely reconstructed although they have been sampled in
several places. Two of the processes end at about the level of the anus and the third enters the
pre-anal ganglia and synapses onto PVC (ALA-d). A single synapse onto the lateral
hypodermis has also been seen on one of the processes (c). Apart from a few rather
unconvincing gap junctions to the excretory canal (b), no other synapses can be unambiguously
assigned to CAN. Laser ablation experiments have, however, shown it to be essential for the
survival of the animal (J. Sulston, unpublished observations).
Magnifications' (a) x 12750, (b, c) x 25500.
170 CEP
LL Y IN ELL DY N
iiiiii, ii~oi,~ ~,ii,~ \ / ....................
c
CEP 171
\ ~-. z!!i~~~~i, '..'., ..... y'~ I
.......... \ / .......... _
Members' CEPDL, CEPDR, CEPVL, CEPVR.
CEP is a set of four neurons with ciliated endings in the cephalic sensilla (figure 1). The
dorsal pair of cell bodies is situated in the pseudocoelomic cavity posterior to the nerve ring
(along with those of URX). The ventral cell bodies are situated anterior to the ring and closely
apposed to the ring neuropile (b). Anteriorly directed processes run in four of the six labial
process bundles to the receptor endings in the head. Posteriorly directed processes emanate
from the ventral CEP pair and loop round the posterior face of the ring neuropile; they then
CEP 173
enter it on the inside surface adjacent to the muscle arms (j, c). The processes branch at this
point and run both ways round the nerve ring on the inside surface near the posterior face of
the ring neuropile. The dorsal branch ends; the ventral branch loops round and runs dorsally
in the middle of the anterior regions of the ring neuropile. The dorsal pair of CEP neurons
send out anteriorly directed processes, which enter the ring near the dorsal mid-line (i) and
then run ventrally on the inside of the ring neuropile adjacent to the muscle arms. These then
loop back and run in the middle of the anterior regions of neuropile, eventually moving back
to the inner surface, where they end. The main synaptic output is to RIC (a, g), AVE (d, f,
h), OLL (f), OLQ. (e), IL1 (e), RMH (g), RMD (h), RMG, URA and URB. CEP synapses
have been shown to contain the neurotransmitter dopamine (Sulston et al. 1975). There is some
synaptic input from OLL, ALM (*c), RIH, RIS, and also from URB (*b) and ADE to the
dorsal pair only. There are gap junctions to OLQ. (*e) and RIH.
Magnifications: (a, e, g) x 25500, (b) x 6375, (c, d, f, h) x 12750.
174 DAn
DA3 DA3 DA8 DA9
AVDL ú
ú ~ AVAR*
ú ~ AVAR
AVER ú
AVEL*
.---~VD3
---~VD3, NMJ
VD3 NMJ ú ~ AVAR*
ú ~ AVAL* i ~ VA12*
AVAL
----~NMJ, VD3
-----~VD3, NMJ
~MJ, VD3
~ VD3, NMJ
..e--- ASII:k ú "",-
VD3, NMJ ú ~ AVAR*
NMJ, VD3 AVAL*
VD3, NMJ ú ~ AVDR
NMJ, VD3
VD3, NMJ ú
NMJ, VD3
VD3, NMJ
---~ NMJ, VD3 ~--AVAL*
NMJ _q ú ~ AVAR*
~. , VI)3 ~ ~--- AVDR*
AVAR*
VD3,NMJ ~ ~ ~ ~+----AVAR* ú ~ AVAR*
NMJ, DD2
VD3, NMJ
'~-- AVDR
......... I--q ....
AVAL*
ú ~ AVAR* ú ~ VA12*
AVDL ú ~ VA12*
VD4,NMJ ~--- AVAR ú ~ AVAL*
ú ~ VA12* ú ~ VA12*
VD4, NMJ
e-~--
NMJ, VD4
ú ~ VA12*
VA12
-~---AVAL e ~ AVAL
ú~ VA12*
ú ~ AVAR*