Movement-related activity in the internal globus pallidus of the parkinsonian macaque.

Abstract

Although the basal ganglia (BG) play a central role in the motor symptoms of Parkinson's disease, few studies have investigated the influence of parkinsonism on movement-related activity in the BG. Here, we studied the perimovement activity of neurons in globus pallidus internus (GPi) of nonhuman primates (NHPs) during performance of a choice reaction time reaching task before and after the induction of parkinsonism by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Neuronal responses, including increases or decreases in firing rate, were equally common in the parkinsonian brain as seen before MPTP, and the distribution of different response types was largely unchanged. The slowing of behavioral reaction times and movement durations following the induction of parkinsonism was accompanied by a prolongation of the time interval between neuronal response onset and movement initiation. Neuronal responses were also reduced in magnitude and prolonged in duration after the induction of parkinsonism. Importantly, those two effects were more pronounced among decrease-type responses, and they persisted after controlling for MPTP-induced changes in the between-trial variability in response timing. Following MPTP, the trial-to-trial timing of neuronal responses also became uncoupled from the time of movement onset and more variable in general. Overall, the effects of MPTP on temporal features of GPi responses were related to the severity of parkinsonian motor impairments, whereas changes in response magnitude and duration did not reflect symptom severity consistently. These findings point to a previously underappreciated potential role for abnormalities in the timing of GPi task-related activity in the generation of parkinsonian motor signs.NEW & NOTEWORTHY Although the globus pallidus internus (GPi) plays a central role in the cardinal symptoms of Parkinson's disease (PD), how parkinsonism alters the movement-related activity of GPi neurons remains understudied. Using a monkey model of PD, we found that: 1) the timing of GPi responses became uncoupled from movement onset; and 2) responses, especially decrease-type responses, became attenuated and prolonged. These abnormalities in GPi perimovement activity may contribute to the generation of parkinsonian motor signs.