Dopaminergic Modulation of Corticostriatal Activity

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DESCRIPTION(As provided by Applicant): This research examines the dopaminergic modulation of cortically-driven striatal immediate-early gene (lEG) expression. Cortical disinhibition induces Fos expression in the dorsolateral portion of the striatum in rats. Previous research has shown that dopamine (DA) has differential effects on striatal neurons, and thus it may modulate striatal response to cortical input. In addition, although the main target of DA-ergic input to the basal ganglia (BG) is the striatum, other BG nuclei receive DA-ergic afferents. The globus pallidus (GP) is an area of the BG that is directly modulated by DA and it also has efferent projections to the striatum. Thus the GP is an area in which DA-ergic modulation can affect striatal function. The specific aims are: 1) to examine the pattern of cortically driven striatal lEG response in subpopulations of striatal neurons by using double-labeling ICC techniques to visualize Fos and parvalbumin (PV); 2) to examine changes in this pattern due to dopamine depletion; 3) to examine changes in this pattern due to blockade of DA receptors in the GP, using intrapallidal application of sulpiride; and 4) to examine changes in this pattern due to stimulation of DA receptors in the GP using inirapallidal application of quinpirole. By examining the effects of DA, both in the striatum and in the GP, on cortically driven striatal lEG response information will be gained about how DA modulates basal ganglia functioning. This information may provide a basis for understanding mechanisms involved in motor disorders such as Parkinson's disease, and may provide important insights into possible extra-striatal targets for therapeutic interventions.