The aim is to obtain more precise description of internuclear relationship among the subthalamus (STh), the substantia nigra (SN), and the globus pallidus (GP). The problems of interest will be addressed with intensive usage of the well established methodology in our laboratory whereby intracellular recordings and labeling with HRP and neuropharmacological analysis in an in vitro preparation, light and electronmicroscopic analysis of the structures labeled by axonally transported PHA-L lectin and localized by immunohistochemical method. Intracellular recordings are intended to reveal synaptic actions, cell firing patterns and membrane characteristics, neuropharmacological analysis to reveal actions of putative transmitters suspected to operate in these circuits, PHA-L immunohistochemistry to reveal morphological features, at both light and ultrastructural level, of the subthalamic, pallidal and nigral axonal terminals and terminal plexus. The convergent multidisciplinary analysis of physiology, pharmacology and anatomy will be directed, in rats, to the following questions: (1) What are the membrane characteristics of STh, SNr and GP neurons? (2) What is the mode of action of STh inputs to SN and GP, and the suspected putative transmitters? (3) What is the mode of action of GP inputs to STh and the putative neurotransmitters? (4) What is the mode of action of SN inputs to STh and its putative neurotransmitters? (5) What are the morphological features of STh axon terminals in SN and GP, GP and SN terminals in STh? Disequilibria of cholinergic, dopaminergic and GABAergic systems in the basal ganglia are suspected to be involved in the pathophysiology of basal ganglia disease. The research for more specific treatments will be facilitated by clear understandings of specific functional nature of the basal ganglia components (e.g., STh, SN, GP) in terms of physiology, pharmacology and anatomy.
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