Novel Strategies for Improved Chronic Neurochemical Measurements In Vivo

Abstract

The work detailed in this dissertation investigates the challenges of chronic neurochemical measurements in vivo and expands the toolbox of the neuroanalytical chemist working to overcome those challenges. Following the introduction in Chapter 1, Chapter 2 investigates the effects that biofouling has on chronically implanted electrodes, specifically for long-term FSCV. The effects on impedance and reference electrode polarization are explored, and a three-electrode FSCV configuration is designed and employed to mitigate the effects on impedance. Chapter 3 describes the fabrication, characterization, and utilization of an iridium oxide (IrOx) reference electrode. The IrOx reference electrode is shown to perform as well as the conventional Ag/AgCl-wire reference electrode in vitro and in vivo, with the additional benefit of biocompatibility. IrOx has the capability to provide a stable reference potential for chronic FSCV in animals and eventually humans. Chapter 4 details the design and employment of an Ommaya-reservoir-based probe for chronic, minimally invasive collection of cerebrospinal fluid (CSF) from non-human primates (NHPs). The development and optimization of an ion-pair HPLC method with electrochemical detection for neurochemical analysis of the collected CSF is described. The use of this novel collection strategy to investigate the effects of vagus nerve stimulation on CSF neurotransmitter levels is explored. Additionally, the behavioral characteristics of NHPs during the completion of custom-written visual learning tasks involving social hierarchy are studied. Combination of these behavioral observations with CSF neurotransmitter analysis via Ommaya reservoir is feasible and would allow for novel insight into the relationships between neurotransmission, social hierarchy, and learning. Together, the work presented in this dissertation offers novel insights, tools, and strategies toward making accurate and meaningful neurochemical measurements in vivo and paves the way for further advancements in the field of chronic in vivo neurochemistry.