Recent anatomic and physiologic studies have demonstrated that the areas of the ventrolateral (VL) thalamus which receive output from the cerebellum (VPLo) and basal ganglia (VLo) are discrete and non- overlapping and that these thalamic subregions project to separate cortical areas. These data suggest the existence of parallel, functionally segregated, thalamocortical circuits which subserve different roles in motor control and the expression of abnormal movements. To test this hypothesis we will examine the physiologic properties of these thalamic subnuclei and the changes associated with cerebellar tremor in the monkey cerebellar tremor subnuclei and the changes associated with cerebellar tremor in the monkey cerebellar tremor model, using quantitative behavioral assessment, single cell recording and microstimulation in the monkey VL thalamus. Cerebellar tremor will be produced by fiber-sparing lesions in the dentate nucleus. We will also assess the effects of fiber-sparing lesions of specific VL subnuclei on motor performance in both normal monkeys and the monkey model of cerebellar tremor. In parallel with the studies in the monkey, we will examine, in humans with cerebellar tremor, the effects of thalamotomy on motor performance and tremor and compare these findings to those in the monkey. These experiments will employ: 1) a passive displacement behavioral paradigm to assess muscle tone, long-latency reflexes, tonic reflexes, and neuronal responses to sensory inputs; 2) a visuo-motor step-tracking task to assess reaction time, movement time, velocity and acceleration profiles, scaling and timing of EMG activity and task-related neuronal activity. These studies will provide a firm test of the hypothesis of functionally segregated circuits, clarify the differential role of VL subnuclei in motor performance and tremor, and provide greater insight into mechanisms which underlie both normal and abnormal movements. These studies may lead to the development of new therapeutic strategies for the treatment of movement disorders.
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