Département de pharmacologie-physiologie, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, QC, Canada.
Department of Medical Neuroscience, Atlantic Mobility Action Project, Brain Repair Center, Dalhousie University, Halifax, NS, Canada.
Front Neural Circuits. 2021 Apr 9;15:639900. doi: 10.3389/fncir.2021.639900. eCollection 2021.
A key function of the mesencephalic locomotor region (MLR) is to control the speed of forward symmetrical locomotor movements. However, the ability of freely moving mammals to integrate environmental cues to brake and turn during MLR stimulation is poorly documented. Here, we investigated whether freely behaving mice could brake or turn, based on environmental cues during MLR stimulation. We photostimulated the cuneiform nucleus (part of the MLR) in mice expressing channelrhodopsin in Vglut2-positive neurons in a Cre-dependent manner (Vglut2-ChR2-EYFP) using optogenetics. We detected locomotor movements using deep learning. We used patch-clamp recordings to validate the functional expression of channelrhodopsin and neuroanatomy to visualize the stimulation sites. In the linear corridor, gait diagram and limb kinematics were similar during spontaneous and optogenetic-evoked locomotion. In the open-field arena, optogenetic stimulation of the MLR evoked locomotion, and increasing laser power increased locomotor speed. Mice could brake and make sharp turns (~90°) when approaching a corner during MLR stimulation in the open-field arena. The speed during the turn was scaled with the speed before the turn, and with the turn angle. Patch-clamp recordings in Vglut2-ChR2-EYFP mice show that blue light evoked short-latency spiking in MLR neurons. Our results strengthen the idea that different brainstem neurons convey braking/turning and MLR speed commands in mammals. Our study also shows that Vglut2-positive neurons of the cuneiform nucleus are a relevant target to increase locomotor activity without impeding the ability to brake and turn when approaching obstacles, thus ensuring smooth and adaptable navigation. Our observations may have clinical relevance since cuneiform nucleus stimulation is increasingly considered to improve locomotion function in pathological states such as Parkinson's disease, spinal cord injury, or stroke.
中脑运动区（MLR）的一个关键功能是控制向前对称运动的速度。然而，自由活动的哺乳动物在 MLR 刺激下整合环境线索制动和转弯的能力记录甚少。在这里，我们研究了在 MLR 刺激期间，自由活动的小鼠是否可以根据环境线索制动或转弯。我们使用光遗传学以 Cre 依赖性方式在表达通道视紫红质的 Vglut2 阳性神经元（Vglut2-ChR2-EYFP）的小鼠中光刺激楔状核（MLR 的一部分）。我们使用深度学习检测运动。我们使用膜片钳记录来验证通道视紫红质的功能表达和神经解剖学来可视化刺激部位。在线性走廊中，自发和光遗传学诱发运动期间步态图和肢体运动学相似。在开阔场中，MLR 的光遗传学刺激引起运动，增加激光功率增加运动速度。在开阔场中的 MLR 刺激期间，当接近角落时，小鼠可以制动并进行急转弯（~90°）。转弯时的速度与转弯前的速度以及转弯角度成比例。在 Vglut2-ChR2-EYFP 小鼠中的膜片钳记录显示，蓝光诱发 MLR 神经元的短潜伏期尖峰。我们的结果加强了这样一种观点，即不同的脑干神经元在哺乳动物中传递制动/转弯和 MLR 速度指令。我们的研究还表明，楔状核的 Vglut2 阳性神经元是一个相关的靶点，可以在不阻碍接近障碍物时制动和转弯的能力的情况下增加运动活性，从而确保平稳和适应性的导航。我们的观察结果可能具有临床意义，因为楔状核刺激越来越被认为可以改善帕金森病、脊髓损伤或中风等病理状态下的运动功能。
