THE PRIMATE SUBTHALAMIC NUCLEUS .3. CHANGES IN MOTOR BEHAVIOR AND NEURONAL-ACTIVITY IN THE INTERNAL PALLIDUM INDUCED BY SUBTHALAMIC INACTIVATION IN THE MPTP MODEL OF PARKINSONISM

1. The effects of reversible and irreversible pharmacological manipula tions of the neuronal activity in the subthalamic nucleus (STN) on par kinsonian motor signs and neuronal activity in the internal segment of the globus pallidus (GPi) were studied in African green monkeys rende red parkinsonian by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydr opyridine. 2. Muscimol injections (less than or equal to 1 mu l, 1 mu g/mu l) into STN reduced neuronal activity recorded at the injection s ite within minutes. This was immediately followed by reduced akinesia, tremor, and rigidity, as well as the emergence of dyskinesias in cont ralateral limbs. The motor effects were accompanied by generalized beh avioral activation, lasted between 10 and 60 min, and were strongly de pendent on the site of injection, with injections into the lateral ''a rm area'' of STN first affecting contralateral arm movements and injec tions into the ''leg'' area affecting leg movements first. 3. Bicucull ine injections (less than or equal to 1 mu l, 1 mu g/mu l) into STN ma rginally increased the neuronal activity and induced neuronal discharg e in bursts. Rigidity, akinesia, and tremor in the contralateral limbs were not changed. 4. Injections of ibotenic acid in two animals (2 an d 7 mu l, 10 mu g/mu l) resulted in 70 and 51% destruction of STN, res pectively. Similarly to the muscimol injections, this resulted in a re duction of the neuronal activity, a reversal of parkinsonian motor sig ns, and the development of dyskinesias in the contralateral limbs. 5. Although tremor was significantly reduced after STN lesions, periodic oscillatory neuronal activity in GPi persisted. The strength of modula tion of the neuronal oscillation was not significantly changed after S TN lesion. 6. The percentage of cells in GPi exhibiting increases in d ischarge in response to torque application was significantly reduced a fter STN lesion. The magnitude and duration of the responses with incr ease in firing rate were reduced after STN lesioning. 7. These results support the hypothesis that abnormally increased tonic and phasic act ivity in STN leads to abnormal GPi activity and is a major factor in t he development of parkinsonian motor signs. Furthermore they imply tha t cells in the basal ganglia have the intrinsic property of dischargin g in periodic bursts, which is unmasked under parkinsonian conditions.