Howard Hughes Medical Institute, Kavli Institute for Brain Science, Mortimer B. Zuckerman Mind Brain Behavior Institute, Departments of Neuroscience and Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
Department of Integrative Medical Biology, Section of Physiology, Umeå University, Umeå, Sweden.
Nature. 2014 Apr 17;508(7496):357-63. doi: 10.1038/nature13021. Epub 2014 Feb 2.
The precision of skilled forelimb movement has long been presumed to rely on rapid feedback corrections triggered by internally directed copies of outgoing motor commands, but the functional relevance of inferred internal copy circuits has remained unclear. One class of spinal interneurons implicated in the control of mammalian forelimb movement, cervical propriospinal neurons (PNs), has the potential to convey an internal copy of premotor signals through dual innervation of forelimb-innervating motor neurons and precerebellar neurons of the lateral reticular nucleus. Here we examine whether the PN internal copy pathway functions in the control of goal-directed reaching. In mice, PNs include a genetically accessible subpopulation of cervical V2a interneurons, and their targeted ablation perturbs reaching while leaving intact other elements of forelimb movement. Moreover, optogenetic activation of the PN internal copy branch recruits a rapid cerebellar feedback loop that modulates forelimb motor neuron activity and severely disrupts reaching kinematics. Our findings implicate V2a PNs as the focus of an internal copy pathway assigned to the rapid updating of motor output during reaching behaviour.
熟练的前肢运动的精度长期以来一直被认为依赖于由传出运动指令的内部引导副本触发的快速反馈校正,但推断的内部副本电路的功能相关性仍然不清楚。一类涉及哺乳动物前肢运动控制的脊髓中间神经元,颈 propriospinal 神经元 (PN),有可能通过前肢传入运动神经元和外侧网状核的小脑前神经元的双重支配来传递前运动信号的内部副本。在这里,我们研究了 PN 内部副本通路是否在目标导向的伸臂控制中发挥作用。在小鼠中,PN 包括一组可遗传的颈 V2a 中间神经元,其靶向消融会扰乱伸臂,而不影响前肢运动的其他元素。此外,PN 内部副本分支的光遗传学激活募集了一个快速的小脑反馈回路,该回路调节前肢运动神经元的活动,并严重破坏伸臂运动学。我们的研究结果表明,V2aPN 是内部副本通路的焦点,该通路被分配用于在伸臂行为期间快速更新运动输出。