The recent discovery of an internal substructure within the neostriatum has raised the possibility that this important region of the brain may contain two different functional cell groups with different synaptic organizations, as well as different afferent and efferent connections. If so, this raises serious complications for all of the current conceptual models of the function of this important set of forebrain structures. The experiments proposed here will determine the extent to which the two tissue compartments in neostriatum, the patch (or striosomal) compartment and the matrix compartment differ along several functionally important parameters. These are: 1) the ratios of convergence of cortical afferents to neostriatal neurons, 2) the effectiveness of synapses made by cortical fibers onto the neostriatal neurons, and 3) the ionic mechanisms that govern the pattern of repetitive firing of the cells. They will also determine whether or not their are functional synaptic connections that connect cells of the matrix with those of the patches. If such connections do exist, the interneurons responsible for them will be identified, and their synaptic actions will be characterized. The goal of the studies is to refine a quantitative model of the physiological function of the neostriatum as an integrator of afferent synaptic input, and to extend it to include interneuronal communication between patches and matrix and the differences in the intrinsic organization of the two compartments that could alter their integrative functions. The experiments will be performed on a newly developed in vitro slice preparation which includes a portion of the neostriatum and its associated corticostriatal pathway and which thus contains a complete corticostriatal circuit. The patch and matrix compartments will be visualized directly at the time of the experiment by fluorescent mircoscopy in slices prepared from animals given injections of a retrogradely transported fluorescent tracer in a region of the midbrain that receives synaptic inputs exclusively from the patch compartment. New findings from neurochemical, developmental and neuropathological investigations have shown that there are important differences between the patch and matrix compartments that may make them differentially susceptible to neurodegenerative disorders, and to defects in development. Functional differences in the organizational and operational principles that govern the two tissue compartments may explain some of the paradoxical symptoms of these conditions and differences in their responses to various forms of treatment, and could suggest ways of altering the course of these disorders.
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