The subthalamic nucleus (STN) is critical for the execution of intended movements. Loss of its normal function is strongly associated with several movement disorders, including Parkinson's disease for which the STN is an important target area in deep brain stimulation (DBS) therapy. Classical basal ganglia models postulate that two parallel pathways, the direct and indirect pathways, exert opposing control over movement, with the STN acting within the indirect pathway. The STN is regulated by both inhibitory and excitatory input, and is itself excitatory. While most functional knowledge of this clinically relevant brain structure has been gained from pathological conditions and models, primarily parkinsonian, experimental evidence for its role in normal motor control has remained more sparse. The objective here was to tease out the selective impact of the STN on several motor parameters required to achieve intended movement, including locomotion, balance and motor coordination. Optogenetic excitation and inhibition using both bilateral and unilateral stimulations of the STN were implemented in freely-moving mice. The results demonstrate that selective optogenetic inhibition of the STN enhances locomotion while its excitation reduces locomotion. These findings lend experimental support to basal ganglia models of the STN in terms of locomotion. In addition, optogenetic excitation in freely-exploring mice induced self-grooming, disturbed gait and a jumping/escaping behavior, while causing reduced motor coordination in advanced motor tasks, independent of grooming and jumping. This study contributes experimentally validated evidence for a regulatory role of the STN in several aspects of motor control.

丘脑底核 (STN) 对于执行预期运动至关重要。其正常功能的丧失与多种运动障碍密切相关，包括帕金森病，STN 是深部脑刺激 (DBS) 治疗的重要目标区域。经典基底神经节模型假设两条平行通路（直接通路和间接通路）对运动施加相反的控制，其中 STN 在间接通路内起作用。 STN 受抑制性和兴奋性输入调节，并且本身具有兴奋性。虽然这种临床相关大脑结构的大多数功能知识都是从病理条件和模型（主要是帕金森病）中获得的，但其在正常运动控制中作用的实验证据仍然较少。这里的目标是梳理 STN 对实现预期运动所需的几个运动参数的选择性影响，包括运动、平衡和运动协调。在自由移动的小鼠中使用双侧和单侧 STN 刺激进行光遗传学激发和抑制。结果表明，STN 的选择性光遗传学抑制增强了运动，而其激发则减少了运动。这些发现为 STN 基底神经节模型的运动提供了实验支持。此外，自由探索小鼠的光遗传学激发会诱导自我梳理、步态紊乱和跳跃/逃跑行为，同时导致高级运动任务中的运动协调性降低，而与梳理和跳跃无关。这项研究为 STN 在运动控制的多个方面的调节作用提供了经过实验验证的证据。