Spinal circuits for sensorimotor integration and interlimb coordination during locomotion

来自肢体的体感反馈对于脊髓损伤后的运动及其恢复至关重要。实现 稳定的运动，脊髓需要处理传入反馈信号，并适当地调节肌肉激活， 肢体间协调交叉反射通路，特别是，是重要的步态稳定性和平衡，这是 在各种运动障碍和老年人中受损。最近，在解码 中枢脊髓运动回路及其脑干指挥系统的组织和功能。但这些互动 在运动过程中，体感反馈与脊髓回路的关系还有待于在同样的细节水平上加以理解。 在这个项目中，我们建议通过结合小鼠遗传学、体内电生理学和 行为分析与脊髓回路和肌肉骨骼系统的计算建模，以系统地剖析 运动回路的感觉传入连接，包括遗传识别的神经元群体，及其 肢体间协调功能。研究交叉反射的组织及其与脊髓运动的相互作用 电路将为康复策略提供关键信息。这一多学科项目将在 两名研究人员之间的密切互动合作，具有强大的和互补的专业知识，在计算（西蒙 Danner，PI）和运动的神经控制的实验研究（Turgay Akay，Co-PI）。该项目有以下内容 三个目的：（1）描述多个脊髓中间神经元参与感觉信息的处理， 通过研究休息和运动时的交叉反射来研究肢体间的协调;（2）设计一个预测性的计算模型， 脊髓运动回路及其与肌肉骨骼系统相互作用的模型;（3）集成建模 和实验来揭示潜在的神经机制该模型将被用来得出信息预测 然后进行实验测试。这个过程的优点是提供了一个明确的和一致的理论 实验框架，从而减少必要的实验数量，同时增加信息 每一个实验都有收获。总之，所提出的多学科方法是基于最先进的实验和 建模方法，并将提供重要的和新颖的见解脊髓运动的神经组织 在运动过程中负责感觉运动整合和肢体间协调的电路，不能通过 实验或建模。

Somatosensory feedback from the limbs is essential for locomotion and its recovery after spinal cord injury. To achieve stable locomotion, the spinal cord needs to process afferent feedback signals and properly adjust muscle activation and interlimb coordination. Crossed-reflex pathways, specifically, are important for gait stability and balance, which are impaired in various motor disorders and in the elderly. Recently, significant progress has been made in decoding the organization and function of the central spinal locomotor circuitry and its brainstem command system. But the interactions of somatosensory feedback with the spinal circuitry during locomotion have yet to be understood on the same level of detail. In this project we propose to address this gap of knowledge by combing mouse genetics, in vivo electrophysiology, and behavioral analyses with computational modeling of spinal circuits and the musculoskeletal system to systematically dissect sensory afferent connectivity to the locomotor circuitry, including genetically identified neuron populations, and their function in interlimb coordination. Studying the organization of crossed reflexes and their interactions with spinal locomotor circuitry will provide critical information for rehabilitative strategies. This multidisciplinary project will be performed in close interactive collaboration between two investigators with strong and complementary expertise in computational (Simon Danner, PI) and experimental studies of neural control of locomotion (Turgay Akay, Co-PI). The project has the following three aims: (1) Delineate the involvement of multiple spinal interneurons in the processing of sensory information and interlimb coordination by studying crossed reflexes at rest and during locomotion; (2) Design a predictive computational model of the spinal locomotor circuitry and its interactions with the mouse musculoskeletal system; (3) Integrate modeling and experimentation to uncover underlying neural mechanisms. The model will be used to derive informative predictions that will then be tested experimentally. This process has the advantage of providing an explicit and consistent theoretical framework for experimentation, thereby reducing the number of necessary experiments while increasing the information gained per experiment. In summary, the proposed multidisciplinary approach is based on state-of-art experimental and modeling methods and will provide important and novel insights into the neural organization of the spinal locomotor circuitry responsible for sensorimotor integration and interlimb coordination during locomotion that cannot be obtained by experimentation or modeling alone.