The function of the basal ganglia in the initiation and elaboration of movement depends upon the generation of properly times episodes of action potential generation by neurons in the neostriatum. The goal of these studies is to determine the anatomical and neurophysiological mechanisms that determine whether or not such an episode will occur in an individual neostriatal neuron, and the timing of these episodes when they do occur. Anatomical experiments will employ intracellular staining with biocytin and light and electron microscopy- to examine the neostriatal innervation from single axons from the largest and most important of the inputs to the neostriatum, the cerebral cortex. The experiments will directly determine the number of synapses made by a single cortical axon which enters the neostriatum, and the volume of neostriatum innervated by one axon. Estimates of the number of synapses made onto one neostriatal neuron by a single cortical axon and the number of axons that contacts each neuron will be made from these data. These estimates will be made separately for three functionally and anatomically different types of corticostriatal cells and for the patch (striosomal) and matrix compartments of the neostriatum. Electron microscopy will be used to identify the identity of postsynaptic neurons, the location of synaptic contacts on the postsynaptic cells, and the morphological features of the synapses formed by each corticostriatal cell type in the patch and matrix compartments. This information is essential to understand how many cortical neurons must be active simultaneously in order to activate a neostriatal neuron. Physiological experiments will use intracellular recording in vivo to determine the firing patterns of corticostriatal neurons that give rise to episodes of activity in neostriatal neurons. This information is analogous to that of the anatomical experiments because it helps to determine the strength of the influence that one cortical neuron may be expected to assert on one neostriatal cell. These experiments will examine each of several types of corticostriatal neurons separately. These experiments provide information required for the interpretation of firing patterns observed during voluntary and goal-directed movements and for interpretation of changes in firing that may accompany disorders of the neostriatum, including Parkinson's disease or Huntington's disease.
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