Date of Award

Summer 8-14-2024

Embargo Period

8-14-2030

Document Type

Thesis

Degree Name

Master of Biomedical Science

Department

Neuroscience

College

College of Graduate Studies

First Advisor

Jennifer Rinker

Second Advisor

Patrick Mulholland

Third Advisor

Rachel Penrod-Martin

Fourth Advisor

Howard Becker

Abstract

Midline thalamic nuclei are a cluster of brain regions known for their involvement in higher-order cognitive functions. In particular, the medio-dorsal thalamus (MDT) is known for utilizing short term memory in order to perform tasks and the paraventricular thalamus (PVT) is known for using feedback for behavior regulation. Both regions are highly interconnected with the infralimbic cortex (IL) and involved in behavioral flexibility and decision making. Alcohol Use Disorder (AUD) has previously been shown to alter decision making, but the underlying mechanism has yet to be determined. While there is some evidence that alcohol influences MDT and PVT function, these effects are not well characterized. Current literature shows that while the pathway between these midline thalamic structures and IL is reciprocal, directionality determines the function. Projections from the MDT to the IL were involved in supporting working memory maintenance while projections from the IL to MDT supported subsequent choice for a task. Likewise, the projections from the PVT to IL consolidate emotionally important memories and the projections from the IL to PVT are involved with behavioral responses. Given the role of these midline thalamic nuclei in mediating aspects of cognitive functions impacted by chronic alcohol exposure, I hypothesized that these brain areas would be activated by alcohol consumption after dependence and inhibition of these regions would reduce alcohol drinking and improve cognitive performance. The Chronic Intermittent Ethanol Exposure (CIE) model of alcohol consumption was used to model alcohol dependence in FosTRAP::Ai14 and DREADD-expressing (designer receptors exclusively activated by designer drugs) C57BL/6J mice to assess the effects of dependence on neural activation and inhibition, respectively. While we see a trend towards increased c-Fos activation in the anterior PVT during alcohol drinking after dependence, the MDT shows significantly more activation compared to water drinking. Despite a slight increase in activation of the PVT, we did not see a significant effect of chemogenetic inhibition of the PVT on alcohol consumption after CIE. Taken together, these results indicate that while the PVT might be engaged by alcohol consumption following induction of dependence, functional inhibition of this region during dependence-induced drinking does not alter consumption.

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Available for download on Wednesday, August 14, 2030

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