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. 2024 Dec 25:2024.12.25.630331. doi: 10.1101/2024.12.25.630331.
The basal ganglia play a crucial role in action selection by facilitating desired movements and suppressing unwanted ones. The substantia nigra pars reticulata (SNr), a key output nucleus, facilitates movement through disinhibition of the superior colliculus (SC). However, its role in action suppression, particularly in primates, remains less clear. We investigated whether individual SNr neurons in three male macaque monkeys bidirectionally modulate their activity to both facilitate and suppress actions and examined the role of glutamatergic inputs in suppression. Monkeys performed a sequential choice task, selecting or rejecting visually presented targets. Electrophysiological recordings showed SNr neurons decreased firing rates during target selection and increased firing rates during rejection, demonstrating bidirectional modulation. Pharmacological blockade of glutamatergic inputs to the lateral SNr disrupted saccadic control and impaired suppression of reflexive saccades, providing causal evidence for the role of excitatory input in behavioral inhibition. These findings suggest that glutamatergic projections, most likely from the subthalamic nucleus, drive the increased SNr activity during action suppression. Our results highlight conserved basal ganglia mechanisms across species and offer insights into the neural substrates of action selection and suppression in primates, with implications for understanding disorders such as Parkinson's disease.
基底神经节在动作选择中起着关键作用，它通过促进期望的动作并抑制不想要的动作来实现。黑质网状部（SNr）作为一个关键的输出核团，通过解除对上丘（SC）的抑制来促进动作。然而，其在动作抑制中的作用，尤其是在灵长类动物中，仍不太清楚。我们研究了三只雄性猕猴的单个SNr神经元是否双向调节其活动以促进和抑制动作，并研究了谷氨酸能输入在抑制中的作用。猕猴执行了一个顺序选择任务，选择或拒绝视觉呈现的目标。电生理记录显示，SNr神经元在目标选择期间放电率降低，在拒绝期间放电率增加，表明存在双向调节。对SNr外侧谷氨酸能输入的药理学阻断破坏了扫视控制，并损害了对反射性扫视的抑制，为兴奋性输入在行为抑制中的作用提供了因果证据。这些发现表明，最有可能来自丘脑底核的谷氨酸能投射驱动了动作抑制期间SNr活动的增加。我们的结果突出了跨物种保守的基底神经节机制，并为灵长类动物动作选择和抑制的神经基础提供了见解，对理解帕金森病等疾病具有启示意义。
