The role of the red nucleus in motor control of skilled and unskilled movements

有人认为，我们的大脑存在是为了产生决定我们行为的动作。我们对大脑特定区域在产生不同运动中的作用的理解仍处于起步阶段。指导我们的研究通常依赖于大脑的损伤或电激活区域。虽然这些方法很有用，但它们不能选择性地激活神经元，而且损伤常常会中断神经通路。在本研究中，我们重点研究了激活红核（RN）对脊髓的投射，这一已知的功能有助于控制运动和熟练的伸手。我们在使用光遗传技术方面获得了丰富的经验，可以选择性地激活和灭活特定的神经回路。我们已经整合了光度法来记录来自RN神经元的具体下降到脊髓。我们现在打算使用这些方法来深入了解当动物进行熟练和不熟练的运动时，已识别的下行RN投射对脑干和脊髓的贡献。目前的建议将提供全脑连接组学、运动功能和技能习得过程中神经元群体活动变化的关键新信息。它建立在我们之前nserc资助的关于运动下降控制的研究项目上。目的1。识别RN电机电路连接组。使用交叉病毒方法，我们将检查从RN到颈脊髓和腹侧髓网状结构（MdV）的投影。病毒方法将使我们不仅可以检测到直接的解剖投影，还可以检测到RN神经元到大脑其他区域的侧支，这是文献中的一个重要空白。2. 在熟练和非熟练的运动任务中检查RN神经元的活动。我们将使用钙指标（GCaMP6）记录rn -脊髓投射神经元的活动。我们将把RN内的活动与EMG活动联系起来，以确定在不同任务期间RN活动相对于EMG活动的延迟。然后，我们将检查随着熟练训练的进展，下行RN神经元的激活随时间的变化。3. 激活和灭活通向颈脊髓的专用RN通路。在这里，我们将测试在控制不熟练的行走（在平地上）、运动过程中熟练的前肢使用和熟练的抓取时，RN对脊髓通路的必要性和充分性。我们将使用组合病毒策略来靶向激活和失活下行RN投射到腹侧髓网状结构或颈脊髓。这项工作将通过使用全脑成像和光遗传学方法检查RN功能连接组，为RN在熟练和非熟练运动的运动控制中的作用提供独特的见解。

It has been argued that our brain exists to produce movements which define our behavior. Our understanding of the role of specific areas of the brain in producing different movements is still in its infancy. Research guiding us often relies on lesioning or electrically activating areas of the brain. While useful, these approaches do not selectively activate neurons, and lesioning often interrupts fibres of passage. In this proposal, we focus on activating red nucleus (RN) projections to the spinal cord, known to contribute to the control of locomotion and in skilled reaching. We have gained extensive experience in the use of optogenetic techniques, to selectively activate and inactivate specific neural circuits. We have integrated photometry approaches to record from RN neurons that specifically descend to the spinal cord. We now intend to use these approaches to gain insight into the contribution of identified descending RN projections to the brainstem and spinal cord when animals are performing skilled and unskilled movements. The current proposal will provide critical new information on whole-brain connectomics, motor function, and on changes in population activity of neurons during skill acquisition. It builds on our previously NSERC-funded research program on descending control of movement.  Aims 1. Identify the RN motor circuit connectome. Using intersectional viral approaches, we will examine the projections from the RN to the cervical spinal cord and the ventral medullary reticular formation (MdV). The viral approach will allow us to detect not only direct anatomical projections but also collateral branching of the RN neurons to other areas of the brain, which is an important gap in the literature. 2. Examine the activity of RN neurons during performance of skilled and unskilled motor tasks. We will record activity from RN-spinal cord projecting neurons using calcium indicators (GCaMP6). We will correlate activity within the RN with EMG activity to determine the latency of RN activity with respect to the EMG activity during the different tasks. We will then examine changes in activation of descending RN neurons over time as skilled training progresses. 3. Activate and inactivate dedicated RN pathways to the cervical spinal cord. Here we will test the necessity and sufficiency of RN to spinal pathways in the control of unskilled walking (over flat ground), skilled forelimb use during locomotion, and skilled grasping. We will use a combinatorial viral strategy to target the activation and inactivation of descending RN projections to either the ventral medullary reticular formation or cervical spinal cord. Significance This work will provide unique insight into the role of the RN in motor control of skilled and unskilled movements by examining the RN functional connectome using whole-brain imaging, and optogenetic approaches.