Neuropeptides are a diverse class of signaling molecules that act as neuromodulators in both vertebrates and invertebrates. C. elegans sensory neurons express an array of neuropeptides that modulate many sensory-mediated locomotory behaviors. In the present study, we have begun to examine the roles of neuropeptides expressed in the polymodal, nociceptive, ASH sensory neurons on aversive behavior.
nlp-15 encodes five predicted peptides and is expressed in the ASHs and a small subset of other neurons. In contrast to wild type animals,
nlp-15 animals exhibit more rapid aversive responses to dilute octanol off food and this phenotype is mimicked by the RNAi knockdown of
nlp-15 in the ASHs of wild type animals and rescued by the ASH expression of
nlp-15. In contrast, the ASH overexpression of
nlp-15 dramatically reduces aversive responses to both 30 and 100% octanol off food. In wild type animals, food/5-HT stimulates aversive responses to dilute octanol and dopamine (DA), tyramine (TA) and octopamine (OA) inhibit food/5-HT stimulation. Food/5-HT also stimulates aversive responses in animals overexpressing
nlp-15 to wild type levels. In contrast, only TA, but not DA or OA, inhibits the increased aversive responses of
nlp-15 null animals off food. To identify the peptide receptors mediating responses to
nlp-15 peptides, over 50 predicted peptide receptor encoding genes were screened, using a combination of null mutants and RNAi feeding in sensitized backgrounds. Animals with predicted null alleles for five receptors exhibited more rapid aversive responses off food than wild type animals, as observed in
nlp-15 null animals. To identify the specific receptor(s) mediating inhibition by
nlp-15 encoded peptides, we are currently overexpressing
nlp-15 in these receptor null backgrounds on the assumption that the inhibition of basal aversive responses associated with
nlp-15 overexpression will be absent in animals with null alleles of the cognate receptor(s). Together, these results suggest that neuropeptides encoded by
nlp-15 inhibit ASH-mediated aversive responses. These studies are continuing to identify and functionally localize the receptor(s) for
nlp-15 encoded peptides by heterologous expression and the neuron-specific rescue of receptor null animals.