To identify mutants that perceive a constitutive state of food deprivation, we screened for mutants that behave as if they had been food-deprived when well fed. Well-fed C. elegans that encounter a bacterial lawn slow their locomotion, exhibiting the basal-slowing response. Acutely food-deprived animals slow more upon entering a bacterial lawn, exhibiting the enhanced-slowing response. Using a
mod-5 deletion background, we screened for mutants that exhibited enhanced slowing in the well-fed state; deletion of
mod-5, which encodes a serotonin reuptake transporter, provided a sensitized strain background facilitating the recovery of mutants. We isolated 17 mutants that were restored to normal locomotion on food by methiothepin, a serotonin-gated receptor antagonist, suggesting that the mutations affect serotonin signaling and the ability to modulate behavior in response to past feeding experience. Two of the 17 mutants,
n4022 and
n3925, failed to complement each other and mapped to a 50 kb region on LG III. We identified a single gene, C44B9.1, capable of rescuing the locomotion defects of
n4022. We identified in the
n4022 and
n3925 strains single point mutations in C44B9.1 predicted to result in premature stop codons. The protein encoded by C44B9.1 has no conserved domains of known function but is significantly similar to uncharacterized proteins found in other organisms, including humans (29% identical, 49% similar). Expression of a C44B9.1 cDNA using a pan-neuronal promoter (
unc-119), but not a body-wall muscle promoter (
myo-3), rescued the locomotion and Hid defects (see below) of
n4022 animals. Using a transcriptional gfp reporter driven by a C44B9.1 promoter, we observed expression in several head neurons, the identities of which we have not yet confirmed. The
n4022 strain has a decreased sensitivity to aldicarb, an acetylcholinesterase inhibitor, and an increased sensitivity to levamisole, an acetylcholine receptor agonist, suggesting that the
n4022 defect may act presynaptically. The drug-sensitivity profile of
n4022 is similar to that of strains mutant for any one of several conserved genes implicated in the regulation of vesicle exocytosis (
unc-64,
unc-31,
hid-1, and
aex-3). Similar to mutations in this group of genes,
n4022 also causes high-temperature (27C) induced dauer (Hid) formation on its own and dauer formation at 25C in combination with
unc-31(
e928) or
unc-64(
e246).