The research of this group examines the organization of the basal ganglia. The basal ganglia are a major neural system through which the cortex affects behavior. As the entire cerebral cortex provides inputs to the basal ganglia it is not surprising that nearly all aspects of behavior are now considered to be affected, to some extent, by the function of the basal ganglia. To date our studies have involved: 1) mapping the neuroanatomical connections of the basal ganglia, 2) characterization of striatal neurons on the basis of their connections and the repertoire of neurochemical markers that they express, and 3) use of quantitative in situ hybridization histochemical (ISHH) analysis of pharmacologically induced regulation of specific subpopulations of striatal neurons to examine the functional organization of the striatum. Neuroanatomical studies have revealed multiple levels of compartmental organization within the striatum that reflect the existence of parallel pathways by which cortical information is processed within the striatum. Characterization of the biochemical phenotypes of striatal neurons contributing to these output pathways reveal their differential expression of repertoires of combinations of transmitter receptor subtypes, second messenger transduction systems, neuroactive peptides and transmitters. We have demonstrated that dopamine differentially regulates the striatopallidal and striatonigral output pathways by the differential expression on neurons contributing to these pathways of the D2 and D1 dopamine receptor subtypes. This provides a model for providing a pharmacologic strategy both for the treatment of Parkinson's disease and for determining the underlying cellular basis of psychostimulant addiction.
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