The experiments outlined in this project will test hypotheses that 1) extend findings on age-related changes in striatal physiology and 2) examine the localization and modulation of nigral Ca2+ currents. These studies will blend morphological and physiological disciplines and apply them to in vitro brain slice, acute neuronal isolation and embryonic mesencephalic culture techniques. Sharp electrode and whole-cell patch clamp techniques will be used for physiological analysis. The theme of the first set of studies is an investigation of mechanisms underlying changes in short-term synaptic plasticity and synaptic reorganization in the aged striatum. Synaptic efficacy and failure rate will be determined through 1) responses to minimal stimulation and 2) an analysis of 4-AP induced spontaneous EPSPs. Postsynaptic striatal cells will be filled with biocytin and examined ultrastructurally to look for relationships between synaptic structure and synaptic plasticity. Lastly, synapses will be experimentally eliminated and the influence of age on reinnervation will be examined physiologically. The theme of the second set of studies is to examine the relationship between dendrites and somatically measured Ca2+ signals. Cortical and nigral lesions will be used to test the hypothesis that synapse elimination induces a reactive dendritic regression that is expressed physiologically as a decrease in the duration of striatal plateau potentials. A second set of experiments will examine the relationship between dendrites and Ca2+ signals by characterizing somatically recorded Ca2+ currents during the postnatal period of dendritic expansion. Acute isolation methods will then be used to examine the impact of dendritic pruning of somatic Ca2+ signals. The third set of studies will test the hypotheses that neurotropins act on dopaminergic substantia nigra neurons through a modulation of 1) Ca2+ currents and 2) afferent synaptic efficacy.
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