Defining the role of the lateral reticular nucleus in skilled forelimb movement

定义外侧网状核在熟练的前肢运动中的作用

• 批准号: 9911895
• 负责人: Elischa Jamal Sanders
• 金额: $ 4.16万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2022-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9911895
• 关键词: Ablation; Address; Ataxia; Axon; Behavior; Biological; Brain Stem; Cell Nucleus; Cerebellum; Cervical; Cervical spinal cord structure; Coffee; Devices; Diagnostic; Electrophysiology (science); Elements; Engineering; Feedback; Felis catus; Fire - disasters; Forelimb; Functional disorder; Goals; Individual; Interneurons; Lateral; Lead; Lesion; Life; Lifting; Limb structure; Molecular Genetics; Monitor; Motor; Motor Neurons; Motor output; Movement; Mus; Muscle; Nervous System Trauma; Nervous system structure; Neurologic Deficit; Neurons; Operative Surgical Procedures; Opsin; Pathway interactions; Patients; Phase; Physiological; Positioning Attribute; Posture; Process; Pronation; Recovery; Reflex action; Role; Route; Sampling; Savings; Sensory; Signal Transduction; Silicon; Sorting - Cell Movement; Source; Specificity; Spinal; Spinal Cord; Structure; System; Therapeutic; Update; Volition; Work; base; behavioral study; cell type; control theory; design; diphtheria toxin receptor; experimental study; extracellular; functional restoration; genetic approach; grasp; improved; in vivo; insight; kinematics; limb movement; molecular marker; mossy fiber; motor control; motor deficit; nervous system disorder; neural prosthesis; neuromechanism; relating to nervous system; sensory feedback; success; theories; tool; transmission process

Project Summary Dexterous forelimb tasks vary in their degree of difficulty, but whether someone is performing a life-saving surgery or reaching for a cup of coffee, the neural mechanisms that underlie these goal-directed movements are poorly understood. Previous studies have shown that as people perform dexterous forelimb tasks, their limb movement is constantly being updated as it traverses through space toward a target. This consistent and rapid updating of forelimb movement suggests that feedback is critical for the success of goal-directed forelimb movements. However, rapid corrections are performed too quickly to be explained purely by sensory feedback, because of delays in the transmission of sensory signals from the body to the nervous system. Neuroscientists have turned to engineering principles of control theory to generate hypotheses regarding the biological elements of motor control. One theory with considerable empirical evidence is that during forelimb movement, internally directed efference copies are sent to the cerebellum, so that the cerebellum can make predictions about the subsequent state of the limb. Generally, evidence for efference copies has been relegated to electrophysiology and/or behavior studies that demonstrate motor output modulation arriving faster than sensory feedback, but the characterization of putative neural structures is lacking. The dearth of evidence characterizing putative neural structures as either sending, processing, or receiving efference copies is due to the difficulties in accessing these structures. However, the use of molecular-genetic tools in the mouse, to selectively access specific cell types within a neural structure, has made potential efference copy circuits more accessible. In order to understand how the cerebellum is using efference copies to generate predictions about subsequent forelimb positions, it is imperative that the pre-cerebellar processing and organization of efference copies are elucidated. The lateral reticular nucleus (LRN) is a pre-cerebellar structure entirely composed of neurons that send mossy fiber projections to the cerebellum. A subset of the input to the LRN comes from the ascending branch of cervical propriospinal interneurons (PNs). PNs are characterized as spinal interneurons receiving descending motor commands and sending bifurcating axonal projections; one branch descending to forelimb motor neurons, and the other branch ascending to the LRN, carrying efference copy information. Therefore, the LRN is an optimal target for evaluating the role of efference copies in skilled forelimb movement. This proposal attempts to investigate the functional role of the LRN in skilled forelimb movement by 1) perturbing LRN function during skilled forelimb movement, and 2) using multi-channel in vivo extracellular recordings to characterize efference copy organization and processing in the LRN. Beyond dissecting motor control circuits, these findings may help improve diagnostics and therapeutics for individuals suffering from devastating motor and neurologic deficits. These findings may also provide strategies for designing and improving neural prostheses.

项目摘要 灵巧的前肢任务在难度上各不相同，但是否有人在执行一个拯救生命， 手术或伸手去拿一杯咖啡，这些目标导向运动的神经机制是 不太了解。先前的研究表明，当人们执行灵巧的前肢任务时，他们的肢体 当运动穿过空间朝向目标时，运动不断地被更新。这种持续而迅速的 前肢运动的更新表明，反馈对于目标导向前肢的成功至关重要 动作然而，快速校正执行得太快而不能纯粹用感觉反馈来解释， 这是因为感觉信号从身体到神经系统的传输延迟。神经学家 我转向控制理论的工程原理来产生关于生物元素的假设 运动控制。一个有大量经验证据的理论是，在前肢运动期间， 定向传出拷贝被发送到小脑，这样小脑就可以预测大脑的活动。 肢体的后续状态。一般来说，传出复制的证据已被降级到电生理学 和/或行为研究，证明运动输出调制比感觉反馈更快到达，但 缺乏对推定的神经结构的表征。缺乏证据表明 结构作为发送，处理或接收传出副本的困难是由于访问这些结构的困难。 结构.然而，在小鼠中使用分子遗传工具，可以选择性地获得特定的细胞类型， 在神经结构中，使潜在的传出复制电路更容易接近。为了解 小脑是如何使用传出复制来预测随后的前肢位置的， 迫切需要前小脑处理和组织的传出副本阐明。横向 网状核（LRN）是小脑前结构，完全由发送苔藓纤维的神经元组成 投射到小脑。LRN的输入的子集来自颈动脉的升分支， 脊髓本体中间神经元（PN）。PNs的特点是接受下行运动的脊髓中间神经元 一个分支下行至前肢运动神经元， 另一个分支上升到LRN，携带输出拷贝信息。因此，LRN是一个最佳的 目标是评估传出复制在熟练前肢运动中的作用。该提案试图 研究LRN在熟练前肢运动中的功能作用，1）在运动过程中扰动LRN功能， 熟练的前肢运动，和2）使用多通道体内细胞外记录来表征传出 LRN中的拷贝组织和处理。除了解剖运动控制回路，这些发现可能有助于 改善了对患有严重运动和神经缺陷的个体的诊断和治疗。 这些发现也可能为设计和改进神经假体提供策略。