Dopamine Replacement Therapy Reverses Abnormal Synchronization of Pallidal Neurons in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Primate Model of Parkinsonism

Abstract

Previous physiological studies have revealed changes in firing rates and synchronization of pallidal neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of Parkinson's disease. Several primate and human studies have demonstrated that dopamine replacement therapy (DRT) reverses the changes in the pallidal firing rates; however, the effects of DRT on pallidal synchronization have never been explored. To do so, we recorded the simultaneous activity of pallidal neurons of a vervet monkey before and after induction of severe parkinsonism by systemic MPTP treatment. We subsequently recorded the pallidal activity before and after daily administration of oral DRT. We extended the time scale of our correlation studies to +/-5 sec to allow detection of long-duration synchronized neuronal activity. After MPTP treatment, firing rates decreased in the external segment of the globus pallidus (GP(e)) and increased in the internal segment (GP(i)). A reversal of these rate changes occurred during the "on" periods of DRT. The percentage of correlated pairs increased from 16.7% in the normal state to 46.9% after MPTP treatment and was restored to nearly normal values (25% correlated pairs) under the influence of DRT. These changes in rate and correlation were observed at both the population level and at the level of units recorded continuously before, during, and after the clinical transition from "off" to "on" periods. We conclude that changes in both pallidal discharge rates and synchronization are correlated with the clinical manifestations of parkinsonism and its pharmacological treatment.