CRCNS: Role of sensory feedback in locomotor recovery after spinal cord injury

描述（由申请人提供）：传入反馈在运动控制和在脊髓损伤（SCI）后体重支持的跑步机训练或产生神经营养因子的细胞移植物的移植物提供的恢复中起关键作用。然而，我们的知识的运动回路的结构是有限的，在恢复的传入反馈的方式和/或起源的作用已经在很大程度上未被探索。我们建议整合的神经模型的运动电路在德雷克塞尔大学医学院开发的生物力学后肢模型在格鲁吉亚理工学院，并使用此集成模型来研究传入反馈的作用，在控制运动在正常条件下，在没有感觉反馈。我们将证明使用的集成模型，在完整的猫的运动控制是依赖于从臀部肌肉的传入反馈的摆动开始，而从脚踝伸肌和/或皮肤输入的传入反馈从脚垫的控制的立场是至关重要的。我们假设，在猫与脊髓损伤，训练或神经营养因子生产的移植增强了感觉反馈的突触强度，这些增加允许电路产生一个稳定的运动模式，在脊髓上的控制。开发的模型将使我们能够调查这一假设，并预测脊髓损伤后某些感觉方式被删除时获得的运动模式缺陷。部分去传入或重新神经支配的肌肉的实验将使我们能够测试这些预测并进一步完善模型。拟议的多学科项目是德雷克塞尔大学医学院和格鲁吉亚理工学院的研究人员之间的合作。计划在这两个地点进行实验，以确定模型参数并验证模型的预测。实验和建模工作将为SCI后感觉反馈在运动恢复中的作用提供新的重要信息。这一建议的知识价值有几个组成部分。首先，一个全面的脊髓运动的神经力学模型将开发，包括猫后肢，运动依赖性本体感受反馈，和中央模式发生器（CPG）。第二，模型参数，包括反馈权重，模态和连接模式内CPG将通过匹配模拟正常和脊髓运动特性与那些实验记录。第三，将使用模型模拟和实验来测试关于感觉反馈在SCI后运动中的作用的几个假设。该模型的结果将增加我们对脊髓运动回路的理解，并可能指导脊髓损伤患者的康复训练工作。该提案将对德雷克塞尔大学的跨部门神经工程计划，医学院的神经科学计划以及格鲁吉亚理工学院的应用生理学和生物医学工程计划产生更广泛的影响，支持学生和博士后研究员从计划中获得，并为他们提供机会，真正整合教育计划中获得的计算和实验神经生理学概念。我们还希望在该项目中开发的模型将用于Lemay和Prilutsky博士在各自机构讲授的神经控制和运动生物力学课程。

DESCRIPTION (provided by applicant): Afferent feedback plays a critical role in the control of locomotion and in the recovery afforded by body-weight supported treadmill training or graft of neurotrophin producing cellular transplants after spinal cord injury (SCI). Yet our knowledge of the structure of the locomotor circuitry is limited and the roles of the modality and/or origin of the afferent feedback in recovery have been for the most part unexplored. We propose to integrate a neural model of the locomotor circuitry developed at Drexel University College of Medicine with a biomechanical hindlimb model developed at Georgia Institute of Technology, and to use this integrated model to study the roles of afferent feedback in the control of locomotion under normal conditions and in the absence of sensory feedback. We will demonstrate using the integrated model that in the intact cat the control of locomotion is dependent on afferent feedback from the hip muscles for the initiation of swing while afferent feedback from the ankle extensors and/or cutaneous input from the foot pad are critical to the control of stance. We hypothesize that in the cat with spinal cord injury, training or neurotrophin producing transplants enhance the synaptic strengths of the sensory feedback and that these increases allow the circuitry to produce a stable locomotor pattern in the absence of supraspinal control. The model developed will allow us to investigate this hypothesis and make predictions about the motor pattern deficits obtained when certain sensory modalities are removed after spinal cord injury. Experiments with partially deafferented or re-innervated muscles will allow us to test these predictions and further refine the model. The proposed multidisciplinary project is a collaboration between investigators at Drexel University College of Medicine and Georgia Institute of Technology. Experiments are planned at both locations to identify model parameters and verify the model's predictions. The experimental and modeling work will provide new and important information about the roles of sensory feedback in locomotor recovery after SCI. The intellectual merit of this proposal has several components. First, a comprehensive neuromechanical model of spinal locomotion will be developed that includes the cat hindlimb, motion-dependent proprioceptive feedback, and central pattern generator (CPG). Second, model parameters including feedback weights, modality, and connectivity patterns within CPG will be identified by matching simulated normal and spinal locomotion characteristics with those recorded experimentally. Third, several hypotheses about the role of sensory feedback in locomotion post-SCI will be tested using model simulations and experiments. The results of the model will increase our understanding of the spinal locomotor circuitry and may guide rehabilitation training efforts in individuals with spinal cord injury. The proposal will have broader impacts on the interdepartmental Neuroengineering program at Drexel University, the Neuroscience program at The College of Medicine, and the Applied Physiology and Biomedical Engineering programs at Georgia Institute of Technology by supporting students and a postdoctoral fellow from the programs and providing them with the opportunity to truly integrate computational and experimental neurophysiological concepts acquired in the educational programs. We also expect the models developed in the project to be used in classes taught by Drs. Lemay and Prilutsky on the neural control and biomechanics of locomotion at their respective institutions.