Biozentrum, Department of Cell Biology, University of Basel, Basel, Switzerland.
Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Nature. 2021 Feb;590(7846):445-450. doi: 10.1038/s41586-020-03080-z. Epub 2021 Jan 6.
The brainstem is a key centre in the control of body movements. Although the precise nature of brainstem cell types and circuits that are central to full-body locomotion are becoming known, efforts to understand the neuronal underpinnings of skilled forelimb movements have focused predominantly on supra-brainstem centres and the spinal cord. Here we define the logic of a functional map for skilled forelimb movements within the lateral rostral medulla (latRM) of the brainstem. Using in vivo electrophysiology in freely moving mice, we reveal a neuronal code with tuning of latRM populations to distinct forelimb actions. These include reaching and food handling, both of which are impaired by perturbation of excitatory latRM neurons. Through the combinatorial use of genetics and viral tracing, we demonstrate that excitatory latRM neurons segregate into distinct populations by axonal target, and act through the differential recruitment of intra-brainstem and spinal circuits. Investigating the behavioural potential of projection-stratified latRM populations, we find that the optogenetic stimulation of these populations can elicit diverse forelimb movements, with each behaviour stably expressed by individual mice. In summary, projection-stratified brainstem populations encode action phases and together serve as putative building blocks for regulating key features of complex forelimb movements, identifying substrates of the brainstem for skilled forelimb behaviours.
脑桥是控制身体运动的关键中心。尽管控制全身运动的脑桥细胞类型和回路的精确性质正在逐渐被揭示,但理解熟练前肢运动的神经元基础的努力主要集中在脑桥以上中枢和脊髓上。在这里,我们定义了在脑桥外侧吻侧区(latRM)中熟练前肢运动的功能图的逻辑。使用在自由活动的小鼠中的体内电生理学,我们揭示了一种神经元编码,latRM 群体对不同的前肢动作进行调谐。这些动作包括伸手和食物处理,这两种动作都因兴奋 latRM 神经元的干扰而受损。通过遗传和病毒追踪的组合使用,我们证明兴奋性 latRM 神经元通过轴突靶部分为不同的群体,通过差异招募脑桥内和脊髓回路起作用。研究投射分层的 latRM 群体的行为潜力,我们发现这些群体的光遗传学刺激可以引发不同的前肢运动,每个行为都由单个小鼠稳定表达。总之,投射分层的脑桥群体编码动作阶段,共同作为调节复杂前肢运动关键特征的潜在构建块,确定了熟练前肢行为的脑桥基础。