Date of Award

5-2020

Document Type

Thesis campus only

Department

Neuroscience

First Advisor

Gerard MJ Beaudoin

Second Advisor

Kah-Chung Leong

Abstract

Exposure to drugs of abuse, such as cocaine, has been known to cause synaptic plasticity, a process that involves changes in receptor expression and receptor-mediated transmission in response to overactivation of a synapse. Cocaine-induced synaptic plasticity has previously been demonstrated in various inputs onto neural pathways involved in motivation and reward, specifically dopaminergic pathways. Our research focused on characterizing cocaine-induced changes at one particular modulatory synapse onto the nigrostriatal dopaminergic pathway: that between the pedunculopontine tegmental nucleus (PPN) and substantia nigra pars compacta (SNc). Prior research has shown that, within the synapse between PPN glutamatergic neurons and SNc dopaminergic neurons, cocaine induces changes in glutamate receptor composition. Based on this finding and the role of cocaine in increasing extracellular dopamine, we wanted to determine whether PPN-SNc plasticity is dependent on one or both dopamine receptor subtypes: excitatory D1-like or inhibitory D2-like. As prior research had implicated D1-like receptors but not D2-like receptors in plasticity in a different dopaminergic pathway, we used a D1-like receptor antagonist to study its effect on cocaine-mediated plasticity at the PPN-SNc synapse. We utilized optogenetics to selectively excite PPN neurons and record current mediated by two ionotropic glutamate receptors: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) and N-methyl-D-aspartate receptors (NMDAR). While the project is still in progress, our data so far seem to diverge from the previously shown cocaine-induced decrease in the AMPA/NMDA ratio, but they suggest that blocking D1-like receptors affects AMPA receptors. These data bring up interesting considerations, such as the existence of SNc subpopulations, that could guide future studies.

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