Yoshida Atsushi, Hikosaka Okihide
Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA; Systems Neuroscience Laboratory, Department of Physiology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido 060-8638, Japan.
Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Curr Biol. 2025 Aug 4. doi: 10.1016/j.cub.2025.07.051.
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.
苍白球外侧段(GPe)传统上被视为基底神经节间接通路中的关键中继站,主要介导运动抑制。然而,最近对啮齿动物的研究表明其作用更为复杂,包括积极促进动作。在此,我们通过记录两只执行新型序列选择任务的猕猴的单单位活动,研究灵长类动物的GPe是否表现出类似的功能多样性。该任务通过要求猴子使用多种策略之一接受“好”物体以获取奖励或拒绝“坏”物体,将动作启动和抑制过程分开。我们根据放电模式识别出三个不同的神经元簇。簇1和簇2与动作促进有关:簇1对两种物体类型的扫视活动均增加,而簇2对好物体扫视有选择性激活,在拒绝时受到抑制——类似于簇3,其在拒绝坏物体时表现出抑制。对尾背GPe内谷氨酸受体进行局部药理学阻断可延长扫视潜伏期并降低拒绝扫视的频率,证实了兴奋性驱动在扫视促进中的因果作用。这些发现扩展了对GPe的传统认识——从单纯的抑制性位点,表明在灵长类动物中,它同时介导运动促进和主动抑制。我们的结果强调了在基底神经节网络中表征GPe的特定回路和特定细胞类型作用的重要性,这对非人类灵长类动物在基于复杂奖励的决策过程中的正常运动功能和运动障碍病理生理学具有启示意义。