Author ORCID Identifier

https://orcid.org/0009-0009-1871-9930

Document Type

Thesis

Date of Award

Spring 4-26-2023

Keywords

Noradrenaline, norepinephrine, sex differences, elevated plus maze, dextran, immunofluorescence, atipamezole, NeuN, medial prefrontal cortex, locus coeruleus

Degree Name

Integrative Neuroscience (BS)

Department

INTEGRATIVE NEUROSCIENCE

First Advisor

Dr. Florence Varodayan

Second Advisor

Dr. Marvin Diaz

Third Advisor

Dr. Anushree Karkhanis

Series

Science and Mathematics

Subject Heading(s)

Mental illness -- Physiological aspects ; Brain -- Physiology ; Noradrenergic mechanisms

Abstract

Rates of anxiety disorders have been increasing in recent years, especially in nations such as the United States. The rates of these diagnoses are not distributed equally amongst the sexes, as women are more prone to being diagnosed with an anxiety disorder, and more likely to be impacted by the disorder more. Noradrenaline (NE) is a major brain stress signal that is made by the locus coeruleus (LC). LC neurons innervate many structures, including the medial prefrontal cortex (mPFC) which is involved in stress and arousal. The female LC is larger and contains more NE-containing neurons. However, it is not known if these additional neurons result in a larger LC to mPFC circuit in females, or whether these sex differences in LC structure lead to differences in brain-wide NE function. Here we increased brain NE levels in male and female mice using the drug atipamezole to indirectly assess how NE may alter anxiety-like behavior differently across sexes. We also began to assess the size of the LC to mPFC circuit in mice of both sexes using retrograde injections of fluorescent tracer. Our results suggest that our hypothesis was wrong and that increasing noradrenaline release led to greater anxiety-like behaviors in male mice compared to female mice. This emphasizes the importance of studying the underlying LC to mPFC circuit.

Available for download on Saturday, April 26, 2025

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