Anatomical and functional characterization of the role of projection-specific populations of corticospinal neurons in motor control

摘要 运动皮质(M1)在控制随意运动中起着至关重要的作用，但神经机制通过 这个区域汇聚在下游电路上的位置仍然不清楚。为了更好地了解M1中的活动 翻译成与语境相适应的行为，我们建议表征特定皮质投射的作用 由其脊髓中间神经元靶标定义的亚型。不断增长的电生理和行为 有证据表明，脊髓中的中间神经元亚群代表着功能单位，当被招募时， 在强加一种适合任务的肌肉激活模式方面发挥作用。这方面的一个例子见 相对的屈肌和伸肌的交替活动，部分由特定的脊椎环路调节。 这些回路可以被覆盖，以实现同时拮抗肌肉的共同激活。两个抑制性脊椎 中间神经元(IN)群、突触前GABA能(GABApre)和相互抑制的GABA/甘氨酸(Ia) 神经元在这一转变中发挥作用，分别经历其活动的激活或抑制。vbl.使用 一种新开发的基于CVS-N2C的狂犬病追踪策略结合对特定基数的遗传访问 对于中间神经元群体，我们已经确定这两类神经元都接受直接的皮质脊髓神经元(CSN)输入。 此外，这一输入被认为在从交替转换到任务适当的转换中发挥了作用 屈肌-伸肌对的激活到共激活。为了调查这一角色的性质，我们有 开发了一项运动行为任务，训练小鼠交替或共同收缩相反的前肢 肌肉对视觉提示的反应。第一次，我们现在可以同时监控和操纵 运动皮质依赖行为中特定的CSN亚集的活动。

Abstract Motor cortex (M1) plays a crucial role in the control of voluntary movement but the neuronal mechanisms by which this region converges on downstream circuits remain obscure. To better understand how activity in M1 is translated into context-appropriate behaviors, we propose to characterize the role of specific cortical projection subtypes as defined by their spinal interneuron targets. A growing body of electrophysiological and behavioral evidence suggests that interneuron subsets in the spinal cord represent functional units that, when recruited, play a role in imposing a task-appropriate pattern of muscle activation. An example of this is seen in the alternating activity of opposing flexor and extensor muscles, which is in part regulated by defined spinal circuits. These circuits can be over-ridden to achieve simultaneous antagonist muscle coactivation. Two inhibitory spinal interneuron (IN) populations, presynaptic GABAergic (GABApre) and reciprocal inhibitory GABA/glycineric (Ia) neurons, play a role in this transition, undergoing activation or suppression of their activity, respectively. Using a recently developed CVS-N2C based rabies tracing strategy combined with genetic access to specific cardinal interneuron populations, we have identified that both classes receive direct corticospinal neuron (CSN) inputs. Moreover, this input has been suggested to play a role in the task-appropriate switching from alternating activation to co-activation of flexor-extensor muscle pairs. In order to investigate the nature of this role, we have developed a motor behavioral task in, which mice are trained to either alternate or co-contract opposing forelimb muscles in response to a visual cue. For the first time, we can now simultaneously monitor and manipulate the activity of defined subsets of CSNs during a motor-cortically dependent behavior.