Defining the contributions of proprioception to goal-directed reaching movements

项目摘要 准确而有效地执行快速、目标导向的移动的能力对于与 环境。这些动作为实验和临床研究提供了一个关键的行为范式。 帮助建立感觉运动控制理论，并确定许多神经科的运动障碍的特征 精神错乱。快速、以目标为导向的移动的准确执行是由互惠的特性实现的 相对肌肉的激活，在时间上精确地加速和减速肢体。许多 整个神经系统的感觉运动障碍(如感觉去传入和小脑疾病)破坏 这一特点是肌肉激活，导致运动能力受损。因此，出现和 打破这种刻板的肌肉招募模式提供了理论和临床方面的见解 感应器马达电路可实现速度和精度。然而，建立和控制这一点的神经机制 相互的肌肉招募仍然难以捉摸，这在很大程度上是因为本体感觉的相对贡献 来自肌肉的反馈还没有明确建立起来。虽然行为观察和 计算模型已经暗示本体感觉反馈在协调肢体运动中的直接作用 这些感觉通路在驱动完整的、行为正常的动物的瞬时精确肌肉激活中的因果作用 一直很难调查。这种挑战在一定程度上是由于传统实验方法的无能为力。 以时间上精确和可逆的方式扰乱特定的神经回路。为了解决这些问题，这 提案将把脊柱感觉运动系统的计算模型与时间上精确的电路结合起来。 具体操作如下：a)选择性本体感觉传入通路和b)一组抑制性 调节行为小鼠本体感觉反馈强度的脊髓中间神经元。具体地说，两个 AIMS将解决关键的悬而未决的问题：1)有哪些具体的本体感觉反馈途径 有助于在肢体加速和减速阶段形成刻板印象的肌肉激活模式 运动，在运动的哪些阶段需要本体感觉反馈(目标1)？2)如何 脊髓中间神经元对反馈强度(增益)的时间精确调制确保适当的肌肉 激活模式(目标2)？这一提议的首要假设是， 激动剂和拮抗剂的肌肉活动在很大程度上依赖于选择性本体感觉的时间精确调节。 反馈途径，而这种反馈的中断会导致异常和不准确的动作。接听 这些问题将有助于揭示由感觉运动路径实现的计算逻辑 准确、高效地执行快速移动，并揭示这些路径的中断是如何产生的 运动障碍。此外，通过定义控制肢体运动的脊椎回路机制，这项工作将 为未来研究下行运动系统如何招募脊髓回路以确保 适当的肌肉激活模式。

Project Summary The ability to perform rapid, goal-directed movements accurately and efficiently is critical for interacting with the environment. These movements have provided a key behavioral paradigm for experimental and clinical study, helping to establish theories of sensorimotor control and to characterize motor impairments in many neurological disorders. The accurate execution of rapid, goal-directed movements is enabled by the characteristic, reciprocal activation of opposing muscles that accelerate and decelerate the limb in a temporally precise manner. Many sensorimotor disorders across the nervous system (e.g. sensory deafferentation and cerebellar disease) disrupt this characteristic muscle activation, leading to impaired motor performance. Therefore, the emergence and disruption of this stereotyped pattern of muscle recruitment offer theoretical and clinical insights into how sensorimotor circuits enable speed and accuracy. Yet the neural mechanisms that establish and control this reciprocal muscle recruitment remain elusive, in large part because the relative contribution of proprioceptive feedback from the muscles has not been clearly established. Although behavioral observations and computational models have implicated proprioceptive feedback in coordinating limb movements, the direct causal role of these sensory pathways in driving temporally precise muscle activation in intact, behaving animals has been difficult to investigate. The challenge is due, in part, to the inability of traditional experimental methods to perturb specific neural circuits in a temporally precise and reversible manner. To address these issues, this proposal will combine a computational model of the spinal sensorimotor system with temporally precise, circuit specific manipulation of the following: a) selective proprioceptive afferent pathways and b) a set of inhibitory spinal interneurons that modulate the strength of proprioceptive feedback in behaving mice. Specifically, two Aims will address key outstanding questions: 1) What are the specific proprioceptive feedback pathways that contribute to stereotyped muscle activation patterns during the acceleration and deceleration phases of limb movement, and during which phases of movement is proprioceptive feedback required (Aim 1)? 2) How does temporally precise modulation of feedback strength (gain) by spinal interneurons ensure appropriate muscle activation patterns (Aim 2)? The overarching hypothesis of this proposal is that the amplitude and timing of agonist and antagonist muscle activity depend critically on temporally precise tuning of selective proprioceptive feedback pathways, and disruption of such feedback causes aberrant and inaccurate movements. Answering these questions will help to uncover the computational logic implemented by sensorimotor pathways for the accurate and efficient execution of rapid movements and reveal how disruption of these pathways produces motor deficits. In addition, by defining spinal circuit mechanisms that control limb movement, this work will lay the groundwork for future studies investigating how descending motor systems recruit spinal circuits to ensure appropriate muscle activation patterns.