| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1991: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1990: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
In order to gain a better understanding of the pathophysiology of dyskinesias in primates, we studied the effects of lesions of the subthalamic nucleus (STN) on neuronal activity in the globus pallidus (GP) of behaving monkeys. Animals were trained to position and hold a manipulandum to which torque pulses were applied, producing elbow flexion and extension. The rate and pattern of single unit discharge in the external (GPe) and internal (GPi) segments of GP was recorded in two monkeys during task performance before and after STN lesions. The STN was lesioned by several injections of small amounts (1.0 mul) of the fiber-sparing neurotoxin, ibotenic acid and/or kainic acid. Postmortem histology confirmed that lesions were confined to the STN and the volume of each lesion was approximately 4-11 % of the total volume of the nucleus.
Severe dyskinesias, involving the proximal joints to a greater degree than the distal, developed in contralateral limbs after 60-80 minutes and lasted 2-4 hours. Dyskinesias were not detected in the ipsilateral limbs. Voluntary movements of the contralateral limb as in reaching were little affected, other than by occasional dyskinesia.
After lesioning, the firing rate of neurons in both segments of GP was significantly (p<0.001) decreased in both animals. The mean discharge rates of GPi neurons decreased from 69.8 spikes/s (n=169, SD=21.6) to 47.4 spikes/s (n=180, SD=22.6) following lesioning. The mean rates of GPe neurons decreased from 63.6 spikes/s (n=218, SD=25.1) before lesioning to 41.0 spikes/s (n=208, SD=18.1) after lesioning.
These results provide further evidence that STN provides a major excitatory input to both segments of the globus pallidus and provide direct supports for the hypothesis that dyskinesias are associated with decreased GPi output.
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