The goal of this program is to investigate the function and development of the basal ganglia using a variety of techniques and preparations. The strength of the proposal has been built from established work in each of six laboratories, whose principal investigators possess diverse backgrounds representing the fields of anatomy, electrophysiology, pharmacology, molecular and cell biology, and behavior. These investigators are united by a common cause; namely to understand the function and development of the basal ganglia under a multidisciplinary and highly interactive research program. We plan to investigate a) development of synapses and order and topography in the neostriatum, b) development of transmitter and morphological phenotype of the striatal neurons and the characterization of their ionic conductances, c) action of putative transmitters on the basal ganglia neurons, d) identification of new putative neurotransmitters in the globus pallidum, e) single-unit activities in the basal ganglia of awake animals, and f) brain graft in the basal ganglia. Project 1 will intend to characterize in the primary dissociated rat explant culture the expression of neurotransmitter and morphological phenotypes using immunocytochemical techniques in conjunction with light and electronmicroscopy, ionic conductances by whole-cell and single-channel voltage clamp techniques, and electrophysiological effects of dopamine on these neurons. Project 2 will examine the action of dopamine and acetylcholine in in vivo rats striatal slice preparation by the intracellular recording technique and morphological relationship between dopamine afferents and striatal neurons. Project 3 study the firing pattern of striatal neurons during the performance of a sensory-triggered movement tasks in the primate. Concomitant anatomical studies, using immunocytochemical tracing combined with light and electronmicroscope are proposed. Project 4 will determine the extent to which the normal cellular connectional arrangements are reproduced in striatal graft by intracellular recording and PHA-L tracing methods in conjunction with light and electron microscopy.
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