Date of Award
Master of Science (MS)
School of Biological Sciences
Paul A Garris
Dopamine (DA) is a neurotransmitter critical for locomotion, motivation, and reward learning and has implications in the neuropathologies of Parkinson’s disease, schizophrenia, and substance use disorder. The rat striatum, which receives the densest DA innervation in the entire rat brain, shows distinct heterogeneity at different anatomical levels, e.g., dorsal and ventral subregions, patch and matrix compartments, and microdomains. The previous use of carbon-fiber microelectrodes (CFM), a single site microsensor coupled to fast-scan cyclic voltammetry (FSCV), has limited the ability to view and characterize this DA heterogeneity. Furthermore, studies examining the effects of amphetamine (AMPH), a psychostimulant with clinical efficacy and high abuse potential, using the CFM may have been biased towards one type of striatal DA signal. Here, I employ a new sensor for characterizing extracellular DA signaling in the rat striatum, the carbon-fiber microelectrode array (CF-MEA). The CF-MEA allows for independent measurements of DA simultaneously at 16 sites with the same analytical features offered by CFMs. Thus, the CF-MEA provides a more complete and unbiased view of striatal DA signaling, because it is not limited to the pitfalls of a CFM optimized to record one signal type. In addition to characterizing a new CF-MEA, whose 9-mm length enables recording in the ventral striatum, I also evaluate a new 32-site FSCV system. For neurobiological applications in the urethan-anesthetized rat, I implant one CF-MEA in the dorsal striatum and one CF-MEA in the ventral striatum for simultaneous 32-site recordings, which demonstrate the heterogeneity of DA across a broad swath of the striatum: 1.5 mm with a 100 µm spatial resolution in the dorsal striatum and 1.8 mm with 120 µm spatial resolution in the ventral striatum. Heterogeneity of DA signaling was demonstrated in the dorsoventral plane by lowering each CF-MEA in 100 µm increments. Moreover, I demonstrate the variability of AMPH effects show additional heterogeneity within DA subdomains and DA signal types. Together, the results indicate that the 32-channel system shows great promise for advancing in vivo neurochemical sensing. Furthermore, the results obtained with the CF-MEA demonstrate the heterogeneity of DA signaling in the striatum on unprecedented dimensions and provide additional insight into the mechanisms of AMPH action.
Chicosky, Rebecca Louise, "Exploring the Heterogeneity of Dopamine Signaling in the Rat Striatum" (2023). Theses and Dissertations. 1725.