Probing dopamine release and function with carbon-fiber microelectrodes

The neurotransmitter dopamine is important in reward processing, however its precise modulatory role is still being investigated. Carbon-fiber microelectrodes can be used to monitor dopamine on a subsecond time scale in the nucleus accumbens of rats. This approach is providing new insights into the mechanisms that control its extracellular concentration as well as the conditions under which it is released. Dopaminergic neurons have been shown to fire in two firing modes, tonic and bursts at higher frequency. Burst firing causes a transient increase in extracellular dopamine whereas tonic firing causes a new steady-state level. In behaving primates, dopaminergic neurons display short-latency, burst firing to primary reward and conditioned cues associated with reward. These bursts code differences between actual and predicted rewards. In rats, transient dopamine release in terminal regions have been demonstrated during reward-related cues.; In order to determine the precise role of dopamine, methods are required which can accurately measure dopamine concentration in the extracellular space. Fast-scan cyclic voltammetry allows selective measurements of dopamine to be made in situ. By enhancing dopamine adsorption at carbon-fiber microelectrode, a lower limit of detection can be achieved. This allows nanomolar concentrations of dopamine to be measured in real-time. I applied principal component regression to analyze cyclic voltammograms for different neurochemicals. This method allows the temporal profile of dopamine and other electroactive substances to be deduced, revealing the temporal profiles of both dopamine and pH changes following cocaine administration.; By combining our electrochemical measurements with electrophysiological measurements, the role of dopamine on neuronal activity can be determined. In this work, electrophysiology recordings were performed between voltammetric scans, meaning both the chemical environment and the cellular activity at the carbon-fiber microelectrode was measured. These studies reveal GABA modulated the changes seen in cell firing during medial forebrain bundle stimulation. Measurements of dopamine in primates also reveal it plays a role in processing reward-related information.