Serotonin (5-HT) modulates a number of key behaviors in C. elegans, including pharyngeal pumping, egg-laying, locomotion, aversive learning and olfaction. For example, Chao et al., 2004 (PNAS, 101:15512) demonstrated that reversal in response to dilute octanol is mediated primarily by the ASH sensory neurons and, more importantly, that 5-HT or bacteria causes animals to reverse more rapidly. To date, four distinct C. elegans 5-HT receptors have been identified, three G-protein coupled receptors, SER-1, SER-4, SER-7 and a 5-HT gated Cl- channel, MOD-1. In the present study, we have examined the effects of 5-HT on sensitivity to dilute octanol in animals containing null alleles of each of these 5-HT receptors, either singly or in combination. Both
ser-1(
ok345) and mod-l
(ok103) null animals failed to respond to 5-HT in these assays and 5-HT dependent increases in octanol sensitivity could be restored in these strains by introducing either a full length
ser-1::gfp transgene with sequence coding for GFP inserted into the predicted SER-1 C-terminus that is expressed in 5 pairs of head neurons (Xiao et al., 2006, Dev. Biol. 298:379) or a full length mod-l transgene, respectively. Interestingly, mod-l
(ok103) null animals also could be rescued with a Podr-2(2b)::
mod-1 transgene that is expressed primarily in the AIB/AIZ primary interneurons. Since neither
ser-1 or mod-l appears to be expressed directly in the ASH, we examined the role of other putative, previously uncharacterized, 5-HT receptors on 5-HT dependent increases in octanol sensitivity by RNAi in an
rrf-3 sensitized background. Indeed, using this approach, we identified a third gene encoding a putative 5-HT receptor that is expressed in a number of sensory neurons, including the ASH, and is required for 5-HT dependent increases in octanol sensitivity. Taken together, these results suggest that at least three 5-HT receptors, located at distinct levels within the sensory/locomotory circuit, are essential for 5-HT dependent increases in octanol sensitivity.