Date of Award

2018

Document Type

Open Access Dissertation

Department

Chemistry and Biochemistry

Sub-Department

College of Arts and Sciences

First Advisor

Parastoo Hashemi

Abstract

Serotonin neurotransmission has multiple facets that are challenging to characterize, due to the lack of analytical tools that can measure serotonin in the brain. In addition, the mechanisms of serotonin modulation by other neurotransmitters, such as histamine, are not well understood. These limitations make the study and treatment of disorders in which serotonin is implicated problematic. This dissertation presents novel electrochemical methods, in addition to the well-established serotonin fast-scan cyclic voltammetry (FSCV), to better understand the dynamics of serotonin and histamine neurotransmission in vivo. In Chapter 1, a method, known as fast-scan controlled adsorption voltammetry, was optimized to selectively and sensitively measure ambient serotonin levels in vivo. In Chapter 2, this newly developed method was combined with FSCV and triple staining immunohistochemistry to confirm that serotonin transporter density affects the reuptake kinetics and ambient levels of serotonin in the CA2 region of the hippocampus and the medial prefrontal cortex. Subsequently, to study the serotonin modulation by histamine, in Chapter 3, an FSCV voltammetry waveform for in vivo measurement of histamine was optimized, that is stable, selective, and sensitive. Through electrical stimulation of the MFB and measuring the evoked histamine signal in the posterior hypothalamus, we showed that serotonin can be simultaneously measured alongside histamine. In Chapter 4, our work was able to demonstrate that histamine has an inhibitory effect on serotonin via the H-3 receptors. This dissertation showcases novel electrochemical techniques that will help pave the way towards a more detailed understanding of the different mechanisms that regulate serotonin neurotransmission in vivo, including neuromodulatory effects by other neurotransmitters. This will enable further work to be carried out in disease models.

Included in

Chemistry Commons

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