Excitatory drive to the globus pallidus external segment facilitates action initiation in non-human primates

Abstract

The external segment of the globus pallidus (GPe) has conventionally been regarded as a key relay in the indirect pathway of the basal ganglia, primarily mediating movement suppression; however, recent studies in rodents suggest a more complex role, including active facilitation of actions. Therefore, we investigated whether the primate GPe exhibits similar functional diversity by recording single-unit activity in two macaque monkeys performing a sequential choice task. This task separated processes of action initiation and suppression by requiring the monkeys to either accept a "good" object for reward or reject a "bad" object using one of multiple strategies. We identified three distinct neuronal clusters based on their firing patterns. Clusters 1 and 2 displayed elevated activity preceding contralateral saccades toward good objects, strongly correlating with shorter reaction times, suggesting a facilitative contribution. In contrast, Clusters 2 and 3 showed decreased activity during rejection of bad objects, reflecting proactive inhibition. Local pharmacological blockade of glutamate receptors within the caudodorsal GPe prolonged saccade latencies and reduced the frequency of rejection saccades, suggesting a causal role for excitatory drive in saccade facilitation. These findings expand the traditional view of the GPe beyond a purely inhibitory station, indicating that in primates it may simultaneously mediate both motor facilitation and proactive suppression. Our results emphasize the importance of characterizing circuit-specific and cell-type-specific roles of the GPe within basal ganglia networks, with implications for normal motor function and movement disorder pathophysiology under complex reward-based decision processes in non-human primates.