The overall goal of this program is to determine the basic mechanisms underlying the regulation of the physiology and pharmacology of basal ganglia amino acid and peptidergic pathways. Within this context, our interests proceed from the behavioral level to the synaptic and molecular level. We are interested in understanding the regulation of the physiological properties of the basal ganglia after selective lesions in relation to motor behavior, the neurotransmitters used in accomplishing this behavior, and the fundamental characteristics of the neurotransmitter receptors that are involved. Our specific goals are as follows: 1. Study the effects of excitotoxic lesions of GABAergic and glutamatergic connections of the basal ganglia on unit activity and motor performance in animals trained to carry out a motor task. 2. Test the hypothesis that the subthalamic nucleus is glutamatergic and is a convergence point for the regulation of striatal and pallidal output and determine whether cortical and thalamic striatal afferents differentially affect striatal neuron subpopulations. 3. Determine the kinetic properties of the GABAA, NMDA and quisqualate receptor channels and the mechanisms by which drugs and ions regulate these properties. 4. Investigate the mechanisms by which neuropeptide Y and somatostatin receptors are coupled to voltage dependent calcium channels.
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