Improving the Collection and Calibration of Voltammetric Measurements of Striatal Dopamine Release

Fast-scan cyclic voltammetry (FSCV) enables rapid and sensitive measurements of electroactive neurochemicals in a variety of organisms, including rodents, non-human primates, and most recently, humans. Many FSCV recordings have focused on the role of the neurotransmitter dopamine, which is implicated in a wide host of different behavioral and pathological states. Experiments using FSCV in conscious rodents have corroborated previous electrophysiology studies that demonstrated dopamine plays a key role in learning, reward-seeking behavior, and the actions of drugs of abuse. The first half of this dissertation concerns studies delving into the role of phasic dopamine release during intracranial self-stimulation (ICSS). In ICSS, subjects are trained to self-administer electrical stimulation of the brain in a manner akin to self-administration of drugs of abuse. Unsurprisingly, given the established role of dopamine in reward-seeking, histological and pharmacological studies have implicated dopamine as a key mediator of this task. However, direct measurements of dopamine release on a timescale relevant to behavior were elusive until the development of FSCV. Early FSCV studies suggested a dissociation between phasic dopamine release and ICSS responding, which stood in stark contrast to evidence from previous reports. Chapter 2 revisits this original finding with the use of more sensitive FSCV measurements and improved calibration methodology, while Chapter 3 extends the study with behavioral and pharmacological manipulations to further probe the relationship between dopamine release and ICSS. The second half of this dissertation pertains to the recent development of chronically-implanted fused-silica microelectrodes (CFMs) for longitudinal FSCV measurements. While these electrodes permit recordings over unprecedented timescales in single recording locations, experimental and practical limitations have required changes in calibration compared to previously established techniques with acutely-implanted glass CFMs. Chapter 4 investigates the potential pitfalls of one approach to calibration, which uses universal models to analyze collected data. Chapter 5 is a collaborative review written with the developers of these electrodes, which addresses similarities and differences between experiments using acutely- or chronically- implanted CFMs, while Chapter 6 describes further characterization and comparison of these two electrode designs. Altogether, the studies in this dissertation suggest improvements for the collection, interpretation, and calibration of FSCV data.Doctor of Philosoph