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: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=689597
• 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，我们的大脑的存在是为了产生定义我们行为的运动。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。这些方法虽然有用，但不能选择性地激活神经元，而且损伤通常会中断通道纤维。在这项提案中，我们重点关注激活脊髓的红核（RN）投射，众所周知，它有助于控制运动和熟练地到达。我们在使用光遗传学技术选择性激活和失活特定神经回路方面获得了丰富的经验。我们采用集成光度测定方法来记录专门下降到脊髓的 RN 神经元。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非熟练运动时，已识别的下降 RN 投射对脑干和脊髓的贡献。目前的提案将提供有关全脑连接组学、运动功能以及技能习得过程中神经元群体活动变化的重要新信息。它建立在我们之前由 NSERC 资助的关于运动下降控制的研究项目的基础上。 ******目标***1。识别 RN 运动回路连接组。***使用交叉病毒方法，我们将检查从 RN 到颈脊髓和腹侧髓质网状结构 (MdV) 的投影。病毒方法不仅能让我们检测到直接的解剖学投影，还能检测到 RN 神经元到大脑其他区域的侧支分支，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 (GCaMP6) 记录 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，以确定不同任务期间 RN 活动相对于 EMG 活动的延迟。然后，随着熟练训练的进展，我们将检查下降 RN 神经元的激活随时间的变化。 ******3.激活和灭活通往颈脊髓的专用 RN 通路。 ***在这里，我们将测试 RN 到脊髓通路在控制非熟练行走（在平坦地面上）、运动过程中熟练前肢使用以及熟练抓握方面的必要性和充分性。我们将使用组合病毒策略来针对腹侧髓质网状结构或颈脊髓的下降 RN 投射的激活和失活。******意义***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。 *****