Presynaptic Partners of Corticospinal Neurons to Control Skilled Movements

在运动行为中高度协调的肌肉激活序列是 直接通过腹侧脊髓运动神经元的微调放电来实现。这些马达 神经元主要由存在于所有哺乳动物中的脊髓中间神经元调节，而这些中间神经元又与 其他脊髓神经元以及各种类型的大脑下行神经元，包括皮质脊髓 (CS)神经元(CSN)。位于运动皮质的CSN连接到脊髓中间神经元以控制运动 神经元在所有物种中的活动，从而协调肢体屈肌和伸肌的活动来控制 熟练的动作。尽管我们和其他人主要关注CSN通过轴突的输出，CSN 也通过它们的树突接受来自突触前神经元的输入。然而，身份识别和 对CSNS(Pre-CSNS)突触前神经元的功能了解仍然有限。我们开发了 以狂犬病病毒为基础的检测，以确定前CSN。我们假设每个前CSN人群将是 明显地被激活以控制熟练动作和肌肉激活的离散阶段。测试我们的 假设，在目标1中，我们将在大脑中定位CSNS的突触前伙伴。我们将进一步确定是否 这些联系是起作用的(目标2)。最后，我们将确定预习CSNS如何掌握前肢技能 运动和肌肉活动(目标3)。这些结果将提供必要的框架， 定义脊髓运动回路，以及随后开发新的有针对性的干预措施来治疗运动 残疾人士。

The highly orchestrated muscle activation sequences during motor behaviors are achieved directly through the fine-tuned firing of motor neurons in the ventral spinal cord. These motor neurons are mainly regulated by spinal interneurons present in all mammals, which are, in turn, connected to other spinal neurons as well as various types of descending neurons from the brain including corticospinal (CS) neurons (CSNs). CSNs located in the motor cortex connect to spinal interneurons to control motor neuron activity in all species, and thereby coordinate the activity of flexor and extensor limb muscles to control skilled movements. Although we and others mainly focused on outputs of CSNs through their axons, CSNs also receive inputs from their presynaptic neurons through their dendrites. However, the identification and understanding of the function of presynaptic neurons of CSNs (pre-CSNs) remains limited. We developed rabies virus-based assays to identify pre-CSNs. We hypothesize that each population of pre-CSNs will be distinctly activated to control discrete phases of skilled movements and muscle activation. To test our hypothesis, in Aim 1 we will map presynaptic partners of CSNs in the brain. We will further determine whether those connections are functional (Aim 2). Finally, we will determine how pre-CSNs control forelimb skilled movements and muscle activity (Aim 3). These results will provide the necessary framework for not only defining spinal motor circuitry, but also subsequent development of novel targeted interventions to treat motor disabilities.