Defense Date

2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Neuroscience

First Advisor

Kurt F. Hauser, PhD

Second Advisor

Pamela E. Knapp, PhD

Third Advisor

A. Rory McQuiston, PhD

Fourth Advisor

Thomas M. Reeves, PhD

Fifth Advisor

Jeffrey L. Dupree, PhD

Abstract

HIV is capable of causing a set of neurological diseases collectively termed the HIV Associated Neurocognitive Disorders (HAND). Worsening pathology is observed in HIV+ individuals who use opioid drugs. Memory problems are often observed in HAND, implicating HIV pathology in the hippocampus, and are also known to be exacerbated by morphine use. HIV-1 Tat was demonstrated to reduce spatial memory performance in multiple tasks, and individual subsets of CA1 interneurons were found to be selectively vulnerable to the effects of Tat, notably nNOS+/NPY- interneurons of the pyramidal layer and stratum radiatum, PV+ neurons of the pyramidal layer, and SST+ neurons of stratum oriens. Each of these interneuron subsets are hypothesized to form part of a microcircuit involved in memory formation. Electrophysiological assessment of hippocampal pyramidal neurons with Tat and morphine together revealed that Tat caused a reduction in firing frequency, however, chronic morphine exposure did not have any effect. When morphine was removed after chronic exposure, non-interacting effects of Tat and morphine withholding on firing frequency were observed, suggesting that a homeostatic rebalancing of CA1 excitation/inhibition balance takes place in response to chronic morphine exposure independently of any Tat effects. Additionally, differential morphological effects of Tat and morphine were observed in each of the three major dendritic compartments, with SR being less affected, suggesting complex circuit responses to these insults reflecting local change and potentially changes in inputs from other brain regions. Behaviorally, Tat and morphine interactions occur in spatial memory, with morphine potentially obviating Tat effects.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

12-13-2017

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