Physiology and Anatomy of the Basal Ganglia

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We have hypothesized that the external segment of the pallidum (GPe) is located at the center of the basal ganglia connections and plays a key role in the physiology and pathophysiology of the basal ganglia. To understand how the neuronal activity of the GPe is controlled under physiological and pathophysiological conditions, the nature of both the synaptic inputs to the GPe neurons and the properties of the postsynaptic membrane should be fully characterized. Anatomical knowledge as well as theories on the basal ganglia motor control predict that the stimulation of the cerebral cortex would induce powerful disynaptic, through the neostriatdum (Str), inhibition in the GPe. However, a striking observation obtained in monkey unit recording study as well as intracellular recording in anesthetized rats was that the cortical stimulation-induced inhibition in the GPe was weak and was dominated by the disynaptic excitation through the subthalamic nucleus (STN). When the STN was chemically blocked, cortical stimulation induced a long duration powerful inhibition in the GPe. Thus, aim 1 is to test a possibility that glutamatergic inputs suppress GABAergic inhibition in the GPe. The STN blockade also caused slow and strong oscillation of GPe neurons. Aim 2 is to investigate the nature of the slow oscillation. Our experiments in the monkey also suggest that GPe neurons receive tonic excitatory input even after the STN blockade. The possible excitatory sources to the GPe, other than the STN, include the centromedian-parafascicular complex (CM-Pf) and the dorsal raphe nucleus. Aim 3 is to study the anatomical and physiological properties of the CM-Pf inputs to the GPe. Aim 4 is to investigate the effects of 5-HT agonists on the GPe neurons and also on the GABAergic synaptic transmissions in the GPe. Experiments will use whole cell recording method in rat brain slice preparations, unit recording method in awake monkeys and an anterograde neurotracing method in the rat. At the end of the proposed projects, we should be able to offer an anatomical and physiological basis for explaining how the synaptic inputs might control the neuronal activity of the GPe.