UCSF

Neuropeptides are a diverse and ancient class of signaling molecule. Many act as neuromodulators, incorporating flexibility into the fixed circuits of the nervous system. In this capacity, neuropeptides subserve one of the nervous system's most important functions - allowing an organism to respond adaptively to changes in its environment. Neuropeptide signaling pathways have been characterized across a range of phyla. Still, many neuropeptides remain poorly understood or altogether undiscovered, and the mechanisms by which pathways interact with each other remain unclear. C. elegans offers a powerful model system for studying neuropeptide signaling. Beyond its genetic tractability and compact nervous system, the worm produces a uniquely large and varied set of neuropeptides. In this work, we use genetic analysis to explore two neuropeptide signaling pathways that modulate C. elegans behaviors. In Part I, we examine the HEN-1 neuropeptide, originally identified for its role in sensory integration. We demonstrate that HEN-1 constitutes a novel signal of food-depletion, and that it regulates foraging, feeding, and egg-laying according to food availability. HEN-1 acts through SCD-2, a receptor tyrosine kinase, and SCD-2 ultimately modulates the activity of tyramine and octopamine, the invertebrate counterparts of epinephrine and norepinephrine. In Part II, we explore a well-known C. elegans social feeding behavior. Social feeding is governed by NPR-1, a member of the neuropeptide-Y receptor family. We establish that reductions in NPR-1 activity enhance the secretion of neuropeptide-containing vesicles. And we show that release of an as yet unidentified neuropeptide drives social feeding.