In recent years, a striking internal organization of the mammalian striatum has been revealed by neuroanatomical and histochemical experiments. Two forms of anatomical heterogeneity have been revealed in the striatum: patches and gradients. Recent autoradiographic studies from the principal investigator's laboratory reveal that the dopamine (D-2) receptor of the striatum shows a marked lateral-to-medial gradient, suggesting an important novel type of heterogeneity in the dopaminergic control of striatal function. Experiments are proposed to characterize and understand the basis for this D-2 heterogeneity. Specific experiments will test (1) whether the striatal D-2 heterogeneity takes the form of patches in a species (rabbit) that displays a patchy organization of acetylcholinesterase, and (2) whether the lateral-to-medial gradient of D-2 receptors in rat caudate-putamen reflects an association of this receptor subtype with cortical afferents to the striatum, intrinsic neurons, or both. Experiments that employ intrastriatal kainic acid injections in neonatal rats or adult dopamine-depleted rats are further designed to test the hypothesis of a preferential association of dopamine D-2 receptor with striatal cholinergic cells.
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