An important feature of the proposed work is its aim to extend the high resolution of single neuron analysis with combined anatomical and histochemical techniques in a direction that will enable more precise description of cytoarchitechtonics of neuronal elements in the basal ganglia and at the same time enable more meaningful interpretation of various nuclear functions of the basal ganglia that can be obtained by conventional single or multiple unit recording or by conventional anatomical technique. The problems of interest will be addressed with intensive usage of the well established methodology in our laboratory whereby intracellular recording and intracellular labeling with horseradish peroxidase are combined with subsequent light and electron microscopic analysis. In addition, histochemical methods including retrograde and anterograde transport techniques and conventional anatomical techniques such and Golgi and Nissl methods will be employed. Immunocytochemical techniques with capability of analysis at light and electron microscopic level and the in vitro slice preparation, pharmacological and ionic manipulations (i.e. microelectrophoresis of transmitter substances and/or substitution of cellular ionic components) will also be incorporated in this convergent multidisciplinary analysis. This methodology will be directed, in species to include rats, cats and monkeys, to the following questions: (1) The intrinsic organization of the striatum (description of morphological substrates for and functional interactions between neuronal elements within the striatum), (2) The extrinsic inputs to the striatum (A further analysis of the nigral, thalamic and cortical inputs), (3) The striatal projection system (Morphological and physiological identification of striatal projection neurons, the course and termination of their axons, and their target neurons), (4) Morphological and physiological identification of pallidal neurons and (5) Morphological and physiological identification of the subthalamic neurons. Disequilibria of cholinergic, dopaminergic, and GABA-ergic systems in the basal ganglia are suspected to be involved in the pathophysiology of basal ganglia disease. The search for more specific treatments will be facilitated my more clear understanding of specific nature of the basal ganglia components and subsequent imbalance of extra-pyramidal operation.
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