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Spinal circuits for sensorimotor integration and interlimb coordination during locomotion

运动过程中用于感觉运动整合和肢体间协调的脊髓回路

基本信息

批准号：
10436335
负责人：
Simon Michael Danner
金额：
$ 33.73万
依托单位：
DREXEL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-21 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10436335
关键词：
Address Anatomy Animals Behavioral Brain Stem Clinical Research Collaborations Comb animal structure Computer Models Contralateral Cutaneous Degenerative Disorder Elderly Electrophysiology (science)Equilibrium Excision Experimental Models Feedback Fiber Foundations Future Gait Gene Delivery Hindlimb Impairment Individual Interneurons Ipsilateral Knowledge Limb structure Literature Local Anesthetics Locomotion Methods Modeling Motor Activity Motor Neurons Mus Muscle Musculoskeletal Musculoskeletal System Mutant Strains Mice Neural Network Simulation Neurons Pathway interactions Pattern Pattern Formation Peripheral Nerves Phase Phase Transition Population Process Public Health Recovery Reflex action Research Personnel Rest Role Sensory Signal Transduction Speed Spinal Spinal Cord Spinal cord injury Surface Syndrome System Testing Virus Wild Type Mouse Work base biomechanical model connectome design experimental study improved in vivo insight interdisciplinary approach kinematics locomotor control motor disorder mouse genetics mouse model multidisciplinary neural circuit neural model neuromechanism neuroregulation novel predictive modeling rehabilitation strategy relating to nervous system response somatosensory tool

项目摘要

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.

肢体的体感反馈对脊髓损伤后的运动及其恢复至关重要。实现