Abstract
Neuromodulators signal through G-protein-coupled receptors to regulate neural circuit activity through a variety of complex signaling pathways. Studies in various systems have found that G-protein signaling pathways can facilitate vesicle release, regulate calcium flow within the cell, activate protein kinases, modulate ion channels, and regulate transcription pathways. Many questions remain, however, about the exact mechanisms by which these pathways regulate neural circuit activity and how distinct G-protein signaling pathways work together to fine-tune the rate and intensity of neural circuit activity in response to signals from other circuits, such as sensory cues. The nematode worm Caenorhabditis elegans has proven to be an invaluable model organism to study the genetic determinants of synaptic transmission. Its simple nervous system and behaviors make it amenable to forward genetic screens using simple phenotype analysis, which have been used to map a diverse array of conserved synaptic and signaling proteins to simple neural circuits. Its transparent body allows for the in vivo use of optogenetic techniques and of transgenically expressed fluorescent proteins, which have been used to identify useful cell-specific promoters, acutely and specifically manipulate cell activity in model circuits, and measure changes in real-time cell activity patterns in response to genetic and acute perturbations. In this dissertation, I present a series of studies in which I have explored how G-protein signaling pathways regulate the egg-laying circuit and tested candidate ion channels as effectors of these pathways.