Date of Award

Fall 2021

Document Type

Open Access Dissertation

Department

Biomedical Science

First Advisor

Parastoo Hashemi

Second Advisor

Lawrence Reagan

Abstract

The monoamine, serotonin, is an important modulator in the central nervous system. It is believed to participate in a variety of functions ranging from moderating stress, promoting brain plasticity, and regulating sleep and appetite. Dysfunction of the serotonergic system has also been implicated in mood disorders and neurodegenerative diseases. While serotonin is of great interest to the research community, real-time in vivo serotonin dynamics remain understudied. This is because direct measurement of fast serotonergic transmission is analytically challenging. In 2009, the Hashemi lab pioneered the direct measurement of endogenously evoked serotonin using a method called fast scan cyclic voltammetry (FSCV). FSCV allows for selective detection of serotonin on a time scale conducive for neurotransmission. This work aims to further our understanding of serotonergic transmission in healthy and disease states. First, we discuss different methods investigating the two uptakes systems for monoamine reuptake into the cell (Chapter 2). Then we review electrochemical serotonin detection and recent findings (Chapter 3). Next, we evaluate serotonin in a toxicological model of Parkinsonism (Chapter 4). This study revealed that mice with lesioned dopamine neurons also have lower concentrations of serotonin in the hippocampus. Furthermore, when given levodopa, dopamine is released at the expense of serotonin production. Finally, we optimized the serotonin waveform to improve electrode sensitivity to serotonin (Chapter 5). When measuring the small signals in the neurodegenerative mice, it became apparent that increased sensitivity was needed for future experiments. We determined that by extending the serotonin waveform to an upper limit of 1.3 V compared to the 1.0 V of the traditional waveform, we could improve serotonin sensitivity while maintaining selectivity. Collectively, this dissertation furthers our understanding of serotonin in mood disorders and neurodegeneration as well as improves our electroanalytical techniques for future studies.

Rights

© 2021, Anna Marie Buchanan

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