Exploring Extracellular Dopamine Concentration and Its Regulation on Dopamine Release by Voltammetry

Extracellular dopamine (DA) is critical in regulating DA release as well as interacting with other neurotransmission systems. Microdialysis and voltammetry are the major techniques for extracellular DA measurement in vivo. These two techniques provide distinct results due to their different detection volumes. Carbon fiber microelectrode is 10,000 times smaller than that of a microdialysis probe. With such a small size, carbon fiber microelectrode provides a high spatial resolution and causes unobservable damage to the brain which paints a completely different picture of DA release in the brain as compared to the knowledge obtained by microdialysis. In Chapter I, with the high temporal and spatial resolution provided by carbon fiber microelectrode in conjunction with fast scan cyclic voltammetry (FSCV), we are able to detect DA terminal populations with different autoinhibition levels in rat striatum. We revealed a coupling between resting DA and local autoinhibition level. The recording sites with high resting DA concentration (M) exhibit a high autoinhibition on evoked DA release induced by medial forebrain bundle (MFB) stimulation, and vice versa. These different types of DA release will never be observed by microdialysis due to its large dimension. On the contrary, microdialysis result is an average of all the DA release sites (high and low) that the microdialysis probe goes through. This averaging method could contribute to the low measurement of the DA concentration by microdialysis. v In Chapter II, we examined the resting DA by a carbon fiber microelectrode at ~200 m away from a microdialysis probe. We found TTX-insensitive DA was decreased by microdialysis probe implantation. This reduction contributes to the low DA measurement by microdialysis. In Chapter III, we monitored evoked DA induced by MFB stimulation in the tissue near microdialysis probe. We found DA terminals near a microdialysis probe are hyper-sensitive to D2 receptor antagonist and DA transporter inhibitor. This suggests that the DA terminals in the tissue near microdialysis probe are under an altered neurochemical state with a loss of DA homeostasis. vi FORWARD First, I would like to thank my research advisor Prof. Adrian C. Michael. During the years of my research and study at University of Pittsburgh, Dr. Michael has provided incredible and insightful guidance to lead me into analytical chemistry. He encouraged me on critical and innovative thinking, educated me to be a scientist, not just a technician. His lab provides all the resources for professional electrochemistry training and collaborations with other …