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, 060-8638, Hokkaido, Japan.
bioRxiv. 2025 Apr 21:2025.04.16.649214. doi: 10.1101/2025.04.16.649214.
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.
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,包括对动作的积极促进。因此,我们通过记录两只进行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来接受“好”的物体以获取奖励或拒绝“坏”的物体,将动作启动和抑制过程区分开来。我们根据它们的放电模式识别出三个不同的神经元簇。簇1和簇2在对侧朝向好物体的扫视之前活动增强,与较短的反应时间密切相关,表明有促进作用。相比之下,簇2和簇3在拒绝坏物体期间活动减少,反映出主动抑制。对尾背侧GPe内谷氨酸受体进行局部药理学阻断会延长扫视潜伏期并降低拒绝扫视的频率,表明兴奋性驱动在扫视促进中起因果作用。这些发现扩展了对GPe的传统认识,使其不仅仅是一个纯粹的抑制性位点,表明在灵长类动物中它可能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。