Date of Award
Fall 2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Neuroscience
First Advisor
Colón-Ramos, Daniel
Abstract
A fundamental goal in neuroscience is to elucidate the cellular and molecular mechanisms that regulate learned behavioral preferences, or memories. While modulation of synaptic connections has been well-established as a component of memory formation, there remains a critical lack in understanding of how specific molecular changes that alter synaptic physiology result in learned behaviors. In this thesis, I utilize the paradigm of learned thermal preferences and the connection between a sensory neuron (AFD) and its postsynaptic partner (AIY) in Caenorhabditis elegans to bridge this gap at the single-synapse level. I first characterize the neurotransmission requirements of this synapse and find that AFD transmits two signals of opposing valence onto AIY: an inhibitory signal that is mediated by glutamate, and an excitatory signal that is refractory to perturbations in chemical neurotransmission. Presynaptic release of glutamate is facilitated by the activity of PKC-1, a highly conserved ortholog of mammalian protein kinase C epsilon, in the AFD neurons and alters behavior by plastically establishing the thermal preference of the ani-mal. Next, I use forward and reverse genetic methods to identify novel effectors of PKC 1, where I find an unexpected role of the Integrator complex in regulating cryophilic behavior produced by constitutively high PKC-1 activity, as well as novel alleles of genes required for normal thermosensory transduction. Finally, I describe efforts to determine the source of AFD’s excitatory output. While it is not mediated by any one gap junction protein that underlies electrical neurotransmission, I extend previous findings that the strength of the excitatory signal may be regulated by a stomatin-like protein MEC-2. Taken together, my work further develops the cell biological principles of regulation at a single synapse that acts to modify animal behavior.
Recommended Citation
Lee, Joon Ha, "Investigating the Synaptic Plasticity Mechanisms Underlying a Learned Behavioral Preference in C. elegans" (2023). Yale Graduate School of Arts and Sciences Dissertations. 1233.
https://elischolar.library.yale.edu/gsas_dissertations/1233
