The overall goal of this program project is to continue our investigation of the function and development of the basal ganglia using a variety of techniques and preparations by a cohesive group of scientists. The strength of this proposal is based on the continuation of a well established program project by a closely linked team of principal investigators (working together for more than five years), who possess diverse backgrounds representing the fields of morphology, electrophysiology, pharmacology, and behavior, AND the addition of two principal investigators and co-investigators whose expertise lie in molecular and cell biology. These additional, closely linked projects and investigators compliment the existing projects and also add another dimension of the cutting edge of science to the existing projects and also add another dimension of the cutting edge of science to the current program. The investigators are united by a common cause; namely, to understand the function and development of the basal ganglia under a multidisciplinary, complementary, and highly interactive research program. Two cores (administrative and central facilities) will be cooperatively shared by investigators for the effective and efficient use of administrative staff, space, and equipment. We plan to investigate: (1.) the elucidation and understanding of molecular changes that occur in target cells of the rat striatum in response to opiate challenge; (2.) the characterization of the molecular and cellular consequences of denervation in the neostriatum; (3.) the enhancement of our understanding of the roles of DA in the control of activities of striatal neurons; (4.) the cellular and molecular mechanisms by which the striatum processes cortical input; (5.) the role basal ganglia play in motor control during stimulus detection and classification, response programming, and selection (initiation) and response production (execution); and (6.) the extent to which grafted striatal neurons possess the characteristic phenotype features of striatal neurons and whether they resemble mature or immature striatal cells.
