ORCID

https://orcid.org/0000-0002-3722-6666

Date of Award

12-17-2024

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

N-methyl-D-aspartate receptors (NMDARs) play an essential role in neuronal function. Activation of NMDARs leads to calcium influx into postsynaptic neurons, which regu?late many fundamental aspects of neuronal physiology including synaptic plasticity, gene expression, and excitability. In the striatum, the input region of the basal ganglia, NM?DAR activity has been shown to regulate physiological function of striatal neurons, such as synaptic plasticity and excitability, and they also modulate behavior, particularly op?erant learning. However, there are many fundamental questions about the signaling and effects of NMDARs in vivo that have yet to be resolved. Moreover, the link between the physiological and behavioral effects of NMDARs has not been investigated. In this Disser?tation, I first show that bulk calcium recordings through fiber photometry is an excellent tool to investigate dendritic calcium changes, since this technique primarily reflects non?somatic changes in calcium. Then, I demonstrate that most striatal calcium signaling is driven by NMDARs, as antagonism of these receptors almost entirely diminish calcium signaling, disrupting the relationship between calcium signaling and action potentials in vivo. Finally, using pharmacological manipulations coupled with home-cage operant learning, I show that NMDARs modulate value-based continuous learning on a trial?by-trial basis, and that antagonism of these receptors disrupts learning of a two-armed bandit task , particularly by diminishing learning from previously rewarded actions. All together, these results demonstrate an essential of NMDARs in both striatal physiology and value-based learning through calcium influx, particularly on a moment-to-moment timescale.

Language

English (en)

Chair and Committee

Alexxai Kravitz

Committee Members

Adam Kepecs; Bryan Copits; Marc Fuccillo; Timothy Holy

Available for download on Monday, June 16, 2025

Included in

Neurosciences Commons

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