Excitotoxic acid lesions of the primate subthalamic nucleus result in reduced pallidal neuronal activity during active holding

Abstract

1. To gain a better understanding of the pathophysiology of hemiballismus in primates, and to test directly the hypothesis that the subthalamopallidal projection is excitatory, we studied the effects of lesions of the subthalamic nucleus (STN) on neuronal activity in the globus pallidus (GP) of monkeys during performance of a motor behavioral task. 2. Animals were trained to position and hold a manipulandum to which torque pulses were applied, producing elbow flexion and extension. The activity of neurons 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 the fiber-sparing neurotoxins ibotenic acid and/or kainic acid. 3. After lesioning, the firing rate of neurons in both segments of GP, which was measured during the period of holding before torque application, was significantly decreased in both animals. The mean of discharge rates of GPi neurons decreased (P < 0.001) from 69.8 (n = 169, SD = 21.6) to 47.4 spikes/s (n = 180, SD = 22.6) after lesioning. The mean of discharge rates of GPe neurons decreased from 63.6 spikes/s (n = 218, SD = 25.1) before lesions to 41.0 spikes/s (n = 208, SD = 18.1) after lesioning. 4. These results provide further evidence that STN gives rise to a major excitatory input to both segments of the GP and support the hypothesis that dyskinesias result from decreased GPi output.