Spinal circuits for sensorimotor integration and interlimb coordination during locomotion

肢体的体感反馈对于脊髓损伤后的运动及其恢复是必不可少的。要实现 稳定的运动，脊髓需要处理传入反馈信号，并适当调整肌肉激活和 四肢间的协调。交叉反射路径对于步态的稳定性和平衡性尤其重要，这是 在各种运动障碍和老年人中受损。最近，在译码方面取得了重大进展 中央脊髓运动回路及其脑干指挥系统的组织和功能。但这种互动 在运动过程中，躯体感觉反馈与脊髓回路之间的关系还没有在相同的细节水平上被理解。 在这个项目中，我们建议通过结合小鼠遗传学、活体电生理学和 行为分析与脊柱环路和肌肉骨骼系统的计算建模，以系统剖析 感觉传入连接到运动回路，包括遗传识别的神经元群体，及其 在四肢间协调中发挥作用。交叉反射的组织及其与脊髓运动相互作用的研究 电路将为康复策略提供关键信息。这一多学科项目将在 在计算方面具有强大和互补专业知识的两名研究人员之间的密切互动合作(西蒙 Danner，Pi)和运动神经控制的实验研究(Turgay Akay，Co-Pi)。该项目具有以下内容 三个目标：(1)描述多个脊髓中间神经元参与感觉信息的处理和 通过研究静息和运动时的交叉反射来研究肢体间的协调；(2)设计一种预测性计算 脊髓运动回路模型及其与小鼠肌肉骨骼系统的相互作用；(3)集成建模 以及揭示潜在神经机制的实验。该模型将被用来得出信息性预测 然后将进行实验测试。这一过程的优点是提供了明确和一致的理论 实验框架，从而减少了必要的实验次数，同时增加了信息 每次实验所获得的收益。总而言之，拟议的多学科方法基于最先进的实验和 建模方法，将为脊髓运动的神经组织提供重要和新颖的见解 运动过程中负责感觉运动整合和肢体间协调的回路，不能通过 单独进行实验或建模。

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.