Date of Award

5-2023

Document Type

Thesis campus only

Department

Biology

First Advisor

Kimberley A Phillips

Second Advisor

Gerard M J Beaudoin

Abstract

Proper functioning of memory, learning, and attention processes relies on regulation of intricate neural networks. Disturbances to neural processing give rise to disease-state symptoms, such as neuronal loss, drug-seeking behavior, and motor dysfunction. To understand the underlying mechanisms which drive these processes, it is necessary to understand how information is encoded and refined by communication between neurons. As such, our research investigates the nigrostriatal dopaminergic pathway by honing in on the synapse between the midbrain structures pedunculopontine tegmental nucleus (PPN) and substantia nigra pars compacta (SNc). The PPN is unusual in that it sends projections to both ipsilateral and contralateral sides of the brain, unlike other brain structures that confine their innervations to either ipsilateral or contralateral. These projections have not been previously studied due to a lack of tools. To understand the nature of these inputs, the current study focuses on glutamatergic excitatory projections and GABAergic inhibitory projections within the PPN-SNc circuit using optogenetics in combination with electrophysiological and confocal microscopic methods. Specifically, we assess how hemisphere-specific inputs differ in their synaptic strength and neurotransmitter make-up. Preliminary findings suggest GABAergic PPN efferents project only to ipsilateral SNc, while glutamatergic PPN efferents project to both ipsilateral and contralateral SNc, with greater strength on the ipsilateral side. Our research will permit greater clarity for future studies to understand the underlying neural network and synaptic-level processes of the nigrostriatal dopaminergic pathway.

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