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he Michael research group in the Department of Chemistry at the University of Pittsburgh focuses on monitoring chemical processes in living animals. Most of the work performed in our lab involves monitoring neurotransmitters in the central nervous system. Often these chemical processes are short lived and are at very low levels making detection very difficult; for this reason we employ electrochemical methods and devices. These methods (cyclic voltammetry, and fast scan cyclic voltammetry) and devices (carbon fiber microelectrodes) provide superior spatial and temporal resolution in the detection of numerous species in vivo making it a useful tool in the neurosciences. Neurochemical events can be observed in real-time. The small size of the electrodes makes this devices particularly suited for delicate systems, such as the brain. These small devices in conjugation with electrochemistry allows us to examine many neurotransmitters like dopamine, serotonin, ascorbic acid and nitric oxide. Many of these species are implicated in various diseases including Parkinson's, schizophrenia, and drug abuse.

Tonic autoinhibition contributes to the heterogeneity of dopamine release

Electrically evoked dopamine release as measured by voltammetry in the rat striatum is heterogeneous in both amplitude and temporal profile. Previous studies have attributed this heterogeneity to variations in the density of dopamine (DA) terminals at the recording site. We reach the alternate conclusion that the heterogeneity of evoked DA release derives from variations in the extent to which DA terminals are autoinhibited. We demonstrate that low-amplitude, slow evoked DA responses occur even though recording electrodes are close to DA terminals. Moreover, the D2 agonist and antagonist, quinpirole and raclopride, respectively, affect the slow responses in a manner consistent with the known functions of pre-synaptic D2 autoreceptors. Recording sites that exhibit autoinhibited responses are prevalent in the dorsal striatum. Autoinhibition preceded electrical stimulation, which is consistent with our prior eports that the striatum contains a tonic pool of extracellular DA at basal concentrations that exceed

Figure: Kinetic heterogeneity of evoked DA release in the rat striatum.

The symbols mark the start (circles) and finish (triangles) of the stimuli. The evoked change in extracellular DA was recorded by FSCV with 400-lm long carbon fiber microelectrodes. (a) A fast-type response: DA increases rapidly during the stimulus and falls rapidly after the stimulus. The amount of DA evoked after the first six stimulus pulses (diamond) is more than half of the amount of DA evoked after 12 pulses (triangle), indicating that the rate of DA release is decelerating. (b) A slow-type response: evoked DA release begins slowly (arrow 1) and accelerates as the stimulus continues (arrow 2). At the end of stimulation the signal returns toward baseline immediately (arrow 3), showing no signs of overshoot.