Measurements of neurotransmitter release in animal models of the central nervous system using fast scan cyclic voltammetry

Abstract

This dissertation is a compilation of the work we have done in the past five years using fast-scan cyclic voltammetry in model organisms to solve biological problems. In this work, we use fast-scan cyclic voltammetry to measure neurotransmitter release in rodent models of neurodegeneration and neurotoxicity. Later, we develop this technique for use in zebrafish whole mount retinas. In Chapter One, we will introduce fast-scan cyclic voltammetry and the underlying electrochemical concepts. We will also introduce the various biological problems investigated in this work and the model organisms used to investigate these problems. In Chapter Two, we will discuss fast-scan cyclic voltammetry measurements of serotonin release in Huntington’s disease model mice. We have demonstrated that serotonin release is impaired in multiple regions of the brain and across multiple mouse models. In Chapter Three, we will discuss fast-scan cyclic voltammetric measurements of both dopamine and serotonin in chemotherapy-treated rats. Here, we have treated rats with both carboplatin and 5-fluorouracil in order to investigate the effect of chemotherapy on neurotransmitter release. Additionally, we will discuss our collaboration with Dr. David Jarmolowicz, in which his lab measured cognitive behavioral changes in rats treated with chemotherapy. We have also investigated the novel drug, KU-32, developed by Dr. Brian Blagg’s group, as a potential therapy for chemotherapy-induced cognitive changes. In Chapter Four, we will discuss our work developing a method to measure light-stimulated neurotransmitter release in adult zebrafish whole mount retinas. Here, we have shown through pharmacological studies that dopamine can be measured using fast-scan cyclic voltammetry in the retina. Finally, in Chapter Five, we will present our conclusions and future directions for this work.