Most models of movement disorders arising from basal ganglia disease, including Huntington's disease, tardive dyskinesia and Parkinsonism, are based upon the concept of striatal dopaminergic-cholinergic balance. Diseases that disrupt this balance result in movement disorders; pharmacological manipulations that tend to restore this balance constitute the usual treatments. A series of experiments is proposed that is designed to elucidate the structural and functional role of the cells that subserve one half of this balance: the neostriatal cholinergic local circuit neurons. (1) Using the method of intracellular recording and HRP filling, type I large neurons will be characterized electrophysiologically and then filled with HRP to reveal their morphology (which will be examined at the light microscopic level). (2) Type I large aspiny neurons, filled by HRP, will be examined at the electron microscopic level and compared to choline acetyltransferase(ChAT)-immunoreactive neurons, with the goal of establishing the identity of the two. (3) The relationship of type I large neurons to the enkephalin-rich patch and enkephalin-poor matrix compartments will be examined using a combined intracellular HRP and immunoperoxidase method. The connections from spiny projection neurons to ChAT-immunoreactive neurons will also be examined with the electron microscope, as will local afferents that are immunoreactive for glutamic acid decarboxylase, enkephalin, and substance P.
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