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

摘要 运动皮层（M1）在自主运动的控制中起着至关重要的作用，但神经元机制， 该区域在下游电路上的收敛仍然不清楚。为了更好地理解M1的活动是如何 翻译成上下文适当的行为，我们建议的特点，具体的皮质投射的作用， 亚型由其脊髓中间神经元靶点定义。越来越多的电生理和行为 有证据表明脊髓中的中间神经元亚群代表功能单位，当被招募时， 在施加任务适当的肌肉激活模式中发挥作用。这方面的一个例子是在 相反的屈肌和伸肌的交替活动，这部分地由限定的脊髓回路调节。 这些回路可以被覆盖以实现同时的拮抗肌共激活。两种抑制性脊髓 中间神经元（IN）群体，突触前GABA能（GABApre）和相互抑制GABA/甘氨酸（Ia） 神经元在这种转变中发挥作用，分别经历其活性的激活或抑制。使用 最近开发的基于CVS-N2 C的狂犬病追踪策略结合了对特定红衣主教的遗传访问， 在中间神经元群体中，我们已经确定这两个类别都接收直接的皮质脊髓神经元（CSN）输入。 此外，这种输入被认为在任务适当的转换中发挥作用，从交替 屈伸肌对的激活到共同激活。为了研究这个角色的性质，我们 开发了一种运动行为任务，其中小鼠被训练交替或共同收缩对侧前肢 肌肉对视觉提示的反应。这是第一次，我们现在可以同时监控和操纵 在运动-皮质依赖行为期间CSN的定义子集的活动。

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.