Defining the contributions of proprioception to goal-directed reaching movements

项目摘要 准确有效地执行快速、目标导向运动的能力对于与 环境这些动作为实验和临床研究提供了关键的行为范例， 帮助建立感觉运动控制的理论，并描述许多神经系统疾病中的运动障碍。 紊乱准确执行快速，目标导向的运动是由特征，互惠， 以时间上精确的方式使肢体加速和减速的相对肌肉的激活。许多 神经系统的感觉运动障碍（例如感觉传入阻滞和小脑疾病）破坏了 这种特征性的肌肉激活，导致运动性能受损。因此，出现和 打破这种刻板的肌肉募集模式提供了理论和临床见解， 感觉运动电路能够实现速度和准确性。然而，建立和控制这一点的神经机制 相互的肌肉募集仍然难以捉摸，在很大程度上是因为本体感受的相对贡献， 来自肌肉的反馈还没有被清楚地建立。虽然行为观察和 计算模型暗示了协调肢体运动的本体感受反馈， 这些感觉通路在驱动完整的、有行为的动物的时间精确的肌肉激活中的因果作用 很难调查这一挑战部分是由于传统的实验方法无法 以时间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， 一个建议将联合收割机的计算模型的脊髓感觉运动系统与时间精确，电路 特异性操纵以下：a）选择性本体感受传入通路和B）一组抑制性 调节行为小鼠本体感受反馈强度的脊髓中间神经元。具体来说，两个 目标将解决关键的悬而未决的问题：1）什么是具体的本体感受反馈途径， 有助于在肢体的加速和减速阶段定型的肌肉激活模式 运动，以及在运动的哪些阶段需要本体感受反馈（目标1）？2)如何 通过脊髓中间神经元对反馈强度（增益）时间精确调节确保适当的肌肉 激活模式（目标2）？这一建议的首要假设是， 激动剂和拮抗剂肌肉活动严重依赖于选择性本体感受的时间精确调谐， 反馈路径，并且这种反馈的中断导致异常和不准确的运动。回答 这些问题将有助于揭示由感觉运动通路实现的计算逻辑， 准确和有效地执行快速运动，并揭示这些途径的中断如何产生 运动障碍此外，通过定义控制肢体运动的脊髓回路机制，这项工作将奠定 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.