Date of Award
Spring 2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Molecular Biophysics and Biochemistry
First Advisor
Koelle, Michael
Abstract
Neurons typically release both a neurotransmitter and one or more neuropeptides in a process known as co-transmission. While this process is a widely observed phenomenon, the logic of why a neuron releases these two or more different types of signals to accomplish its myriad of functions remains largely unclear. In this dissertation, I studied how two serotonergic neurons in the C. elegans egg-laying circuit—known as the Hermaphrodite Specific Neurons (HSNs)—release both the neurotransmitter serotonin and the neuropeptide NLP-3 to activate egg laying. Egg laying typically occurs in a temporal pattern with two-minute active phases, during which the HSNs are highly active and eggs are laid approximately 18 seconds apart. These periods of intense egg laying are separated by approximately 22-minute inactive phases, during which the HSNs have less frequent calcium transients and no eggs are laid. I utilized a targeted RNAi screen to identify the G protein coupled receptor NPR-36 as an NLP-3 receptor, and used additional genetic and molecular experiments to support this cognate pairing. NPR-36 is expressed on and promotes egg laying by activating the egg-laying muscle cells, the same cells where two serotonin receptors also promote egg laying. Although NLP-3 is likely released only when HSNs are highly active (i.e. during the active phase), NLP-3 appears to persist through the subsequent inactive phase to switch on the next active phase along with serotonin. I conclude from this work that NLP-3 and serotonin together overcome the long-lasting inhibitory signals that maintain the egg-laying inactive phase while also regulating discrete aspects of egg-laying activity in the active phase. My work suggests a model in which multiple signals with short and long-lasting effects compete to pattern a behavior over tens of minutes.
Recommended Citation
Butt, Allison, "The Duality of Neurons: Co-transmission of Serotonin and a Neuropeptide, NLP-3, in the Caenorhabditis elegans Egg-Laying Circuit" (2024). Yale Graduate School of Arts and Sciences Dissertations. 1280.
https://elischolar.library.yale.edu/gsas_dissertations/1280
