Guillaumin Adriane, Serra Gian Pietro, Georges François, Wallén-Mackenzie Åsa
Department of Organism Biology, Uppsala University, SE-752 36 Uppsala, Sweden.
Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
Brain Res. 2021 Mar 15;1755:147226. doi: 10.1016/j.brainres.2020.147226. Epub 2020 Dec 23.
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）对于预期动作的执行至关重要。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，而丘脑底核是帕金森病深部脑刺激（DBS）治疗的重要靶点区域。经典的基底神经节模型假定，直接通路和间接通路这两条平行通路对运动发挥相反的控制作用，丘脑底核在间接通路中起作用。丘脑底核受抑制性和兴奋性输入的调节，其本身具有兴奋性。虽然关于这个临床相关脑结构的大多数功能知识是从病理状况和模型（主要是帕金森病模型）中获得的，但关于其在正常运动控制中作用的实验证据仍然较为稀少。这里的目的是梳理出丘脑底核对实现预期动作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。在自由活动的小鼠中实施了对丘脑底核的双侧和单侧光遗传学兴奋和抑制。结果表明，对丘脑底核的选择性光遗传学抑制增强了运动，而其兴奋则减少了运动。这些发现为丘脑底核在运动方面的基底神经节模型提供了实验支持。此外，在自由探索的小鼠中进行光遗传学兴奋会诱发自我梳理、步态紊乱和跳跃/逃避行为，同时在高级运动任务中导致运动协调能力下降，且与梳理和跳跃无关。这项研究为丘脑底核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。
