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

有人认为，我们的大脑是为了产生定义我们行为的运动而存在的。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损伤或电激活大脑区域。虽然有用，但这些方法不会选择性地激活神经元，并且损伤通常会中断通道纤维。在这个提议中，我们专注于激活红核（RN）到脊髓的投射，已知有助于控制运动和熟练的达到。我们在使用光遗传学技术方面获得了丰富的经验，以选择性地激活和激活特定的神经回路。我们已经整合了光度法来记录RN神经元，特别是下降到脊髓。我们现在打算使用这些方法来深入了解的贡献，确定下降RN预测脑干和脊髓时，动物进行熟练和不熟练的运动。目前的提议将提供关于全脑连接组学、运动功能和技能获得过程中神经元群体活动变化的重要新信息。它建立在我们以前NSERC资助的运动下降控制研究计划的基础上。 旨在 1.识别RN运动回路连接体。 使用交叉病毒的方法，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能够检测直接的解剖投影，而且还可以检测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. 检查RN神经元在执行熟练和非熟练运动任务期间的活动。 我们将使用钙指示剂（GCaMP 6）记录来自RN-脊髓投射神经元的活动。我们将RN内的活动与EMG活动相关联，以确定在不同任务期间RN活动相对于EMG活动的延迟。然后，我们将研究随着技能训练的进展，随着时间的推移，下行RN神经元的激活变化。 3.激活并保留专用的RN通路至颈脊髓。 在这里，我们将测试RN的必要性和充分性，以脊髓通路的控制不熟练的步行（在平地上），熟练的前肢使用在运动过程中，熟练的把握。我们将使用一种组合的病毒策略来靶向腹侧髓网状结构或颈脊髓的下行RN投射的激活和失活。 意义 这项工作将提供独特的洞察力的RN在运动控制的熟练和不熟练的运动通过检查RN功能连接体使用全脑成像，和光遗传学的方法。

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.