Student Theses and Dissertations
Date of Award
2019
Document Type
Thesis
Degree Name
Doctor of Philosophy (PhD)
Thesis Advisor
Cori Bargmann
Keywords
C. elegans, nematocin, DVA interneuron, mating behavior, dopamine, oxytocin
Abstract
In the four modalities of analysis that Tinbergen describes: mechanistic, ontological, functional, and phylogenetic, I look at both the "how" and the "why" of oxytocin as a releaser of reproductive behavior. To do so, I take the wide view across 600 million years of metazoan evolution, focusing on the oxytocin-mediated mating behavior and physiology of the often-overlooked invertebrates. By looking to these simpler animals with both smaller, paired-down nervous systems and more diverse sets of mating strategies, I elucidate some of the basic and general principles of the oxytocin circuit (Chapter I). In Chapter II, I give a survey of the ethology of Caenorhabditis (nematode roundworms) mating behavior, before I delve into the experimental investigation of the oxytocin-mediated mating circuit of Caenorhabditis elegans. The compact, fully anatomically diagrammed nervous system of this organism makes it an ideal model for this study, as do the multitude of genetic, molecular, pharmacogenic, optogenetic, and imaging tools available for C. elegans. The singular most critical feature of this animal this study exploits, however, is that I can constitutively knock out the gene for its oxytocin homolog, nematocin, without compromising the health, development, or general locomotion of the animal. In Chapter III, I show that the main source of nematocin in the male's copulatory apparatus (his tail), the interneuron DVA, has activity during mating that is critical for carrying it out competently. I do this by acutely silencing DVA with a heterologous histamine-gated chloride channel and its ligand just prior to mating, then by restoring mating by letting the males recover off histamine. The experiment is repeated in the nematocin-deficient males, to identify which of the behavioral phenotypes are nematocinmediated, and which are not. Next, I discuss a genetic candidate screen to look for a mechanism of nematocin action (Chapter IV). I find that nematocin mutants are epistatic to dopamine mutants, implicating them in the same circuit. The classical interpretation of the genetic result suggests that the severe defect in dopamine deficient animals is due to a dysregulation of nematocin. I then rescue mating in dopamine-deficient males by acutely silencing DVA to corroborate this. In Chapter V I investigate the activity of DVA during mating with the fluorescent calcium indicator GCaMP. I describe an activity pattern for DVA that coordinates calcium signal rises and falls with specific sub-behaviors within the mating behavior. I then look at DVA in nematocin deficient and dopamine-deficient males, and find that DVA activity breaks down at behavioral junctures consistent with the genetic behavioral data. In Chapter VI I identify 2 dopamine receptors responsible for communicating the dopamine signal to DVA, one of which is a D1-like receptor (cAMP activating) and the other of which is a D2-like receptor (cAMP suppressing), and demonstrate their reciprocal effects on mating behavior. In Chapter VII, I summarize the experimental results, contextualize the main implications, and generally discuss oxytocin and dopamine's deep phylogenetic connection in modulating reproductive behavior.
License and Reuse Information
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Recommended Citation
Lockard, Meghan Aileen, "Oxytocin, Dopamine, and the Neuromodulation of Mating Behavior in C. Elegans" (2019). Student Theses and Dissertations. 519.
https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/519
Comments
A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy