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

红核在熟练和非熟练动作的运动控制中的作用

• 批准号: RGPIN-2019-04394
• 负责人: Whelan, Patrick
• 金额: $ 3.42万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=766035
• 关键词: role; red; nucleus; motor; control

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.

有人认为，我们的大脑存在于产生定义我们行为的运动。我们对大脑在产生不同运动中特定领域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病变或电动激活区域。尽管有用，但这些方法并不能选择性地激活神经元，并且病变通常会中断通道的纤维。在此提案中，我们专注于激活红色核（RN）项目，我们在使用光遗传技术方面获得了丰富的经验，以选择性激活和灭活特定的神经元电路。我们采用了集成的光度法方法来记录从RN神经元特别下降到脊髓的RN神经元。现在，我们打算使用这些方法来深入了解当动物执行熟练和非熟练运动时，确定的RN项目对脑干和脊髓的贡献。当前的提案将提供有关全脑连接组学，运动功能以及技能获取过程中神经元人口活动变化的关键新信息。它建立在我们以前由NSERC资助的研究计划的基础上，涉及对运动的下降控制。目标1。识别RN电机电路连接。使用交叉病毒方法，我们将检查从RN到颈脊髓和腹侧髓质网状形成（MDV）的项目。病毒方法将使我们不仅可以检测到解剖学项目，还可以检测RN神经元的附带分支到大脑的其他区域，这在文献中是重要的差距。 2。检查在熟练和非熟练运动任务执行过程中RN神经元的活性。我们将使用钙指标（GCAMP6）记录RN脊髓投射神经元的活动。我们将将RN中的活性与EMG活性相关联，以确定在不同任务中相对于EMG活性的RN活性的潜伏期。然后，随着熟练的训练的进展，我们将随着时间的推移随时间探讨降升RN神经元激活的变化。 3。激活并灭活颈脊髓的专用RN途径。在这里，我们将测试RN的必要和充分性，以控制非熟练行走（在平坦地面上），熟练的前肢在机车过程中使用和熟练的抓握。我们将使用组合病毒策略来针对向腹侧髓质网状形成或颈脊​​髓激活和失活的激活和失活。这项工作的意义将通过使用全脑成像和光遗传学方法检查RN功能连接组，从而为RN在熟练和非熟练运动中的运动控制中的作用提供独特的见解。