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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National Institute of Neurological Disorders and Stroke (NINDS)
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Neurology B Subcommittee 1 (NEUB)
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University of Tennessee Health Science Center
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Kitai, S T (1998) Afferent control of substantia nigra compacta dopamine neurons: anatomical perspective and role of glutamatergic and cholinergic inputs. Adv Pharmacol 42:700-2
Surmeier, D J; Seno, N; Kitai, S T (1994) Acutely isolated neurons of the rat globus pallidus exhibit four types of high-voltage-activated Ca2+ current. J Neurophysiol 71:1272-80
Bargas, J; Howe, A; Eberwine, J et al. (1994) Cellular and molecular characterization of Ca2+ currents in acutely isolated, adult rat neostriatal neurons. J Neurosci 14:6667-86
Kang, Y; Kitai, S T (1993) Calcium spike underlying rhythmic firing in dopaminergic neurons of the rat substantia nigra. Neurosci Res 18:195-207
Kang, Y; Kitai, S T (1993) A whole cell patch-clamp study on the pacemaker potential in dopaminergic neurons of rat substantia nigra compacta. Neurosci Res 18:209-21
Granata, A R; Kitai, S T (1992) Intracellular analysis in vivo of different barosensitive bulbospinal neurons in the rat rostral ventrolateral medulla. J Neurosci 12:1-20
Pennartz, C M; Kitai, S T (1991) Hippocampal inputs to identified neurons in an in vitro slice preparation of the rat nucleus accumbens: evidence for feed-forward inhibition. J Neurosci 11:2838-47
Kita, H; Kitai, S T (1991) Intracellular study of rat globus pallidus neurons: membrane properties and responses to neostriatal, subthalamic and nigral stimulation. Brain Res 564:296-305
Machida, C M; Scott, J D; Ciment, G (1991) NGF-induction of the metalloproteinase-transin/stromelysin in PC12 cells: involvement of multiple protein kinases. J Cell Biol 114:1037-48
Pennartz, C M; Boeijinga, P H; Kitai, S T et al. (1991) Contribution of NMDA receptors to postsynaptic potentials and paired-pulse facilitation in identified neurons of the rat nucleus accumbens in vitro. Exp Brain Res 86:190-8

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