The aim is to examine the role of basal ganglia output in normal and abnormal movement. Specifically, we seek to clarify the pathophysiologic basis of such basal ganglia-related movement disorders as akinesia, bradykinesia, rigidity, and involuntary movements. Because the inner segment of the globus pallidus (GPi) is the major output nucleus of the basal ganglia, the proposed studies will be focused on the analysis of alterations in tonic neuronal activity and phasic movement-related neuronal activity in GPi in association with each of these types of movement disorder. We will examine behaviorally and physiologically two primate models of human movement disorders: the monkey MPTP model of Parkinsonism and the monkey model of hemiballismus. We will also assess the motor effects of local pharmacologic manipulations and lesions of GPi. Changes in task-related neuronal activity will be correlated with normal and altered task performance and muscle tone. Animals will be studied before and after treatment, so that each animal may serve as its own control. Two behavioral paradigms will be employed: a step-tracking task to assess reaction time, movement time, and scaling of movement amplitude; and a torque applications task to assess muscle tone, phasic reflexes and neuronal responses to sensory inputs. Together, these studies should provide new insight into the pathophysiology of the major motor abnormalities resulting from basal ganglia dysfunction and also help to further clarify the role of the basal ganglia in normal movement and the regulation of muscle tone.
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