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 been conventionally 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. Here, we investigated whether the primate GPe exhibits similar functional diversity by recording single-unit activity in two macaque monkeys performing a novel sequential choice task. This task separated the process 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 were linked to action facilitation: cluster 1 increased activity for saccades to both object types, while cluster 2 was selectively active for good-object saccades and suppressed during rejections-similar to cluster 3, which showed suppression during bad-object rejection. Local pharmacological blockade of glutamate receptors within the caudal dorsal GPe prolonged saccade latencies and reduced the frequency of rejection saccades, confirming 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 simultaneously mediates 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.