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

传入反馈在运动控制和脊髓损伤（SCI）后由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，我们的知识的结构的运动电路是有限的，传入反馈的作用，运动恢复已在很大程度上未被探索。该多学科项目将 将德雷克塞尔大学开发的运动回路神经模型与格鲁吉亚理工学院开发的生物力学后肢模型相结合。这个综合模型将被用作一个试验床，以研究传入反馈的作用，在运动的控制在完整的猫和脊髓横断后的运动功能的恢复。我们假设（并使用简化的 模型），来自臀部肌肉的肌肉长度相关反馈对于摆动的开始是关键的，并且来自脚踝伸肌的力反馈和来自脚垫的皮肤输入对于站立的控制是关键的。我们还假设，在脊髓猫中，训练或产生神经营养因子的移植物增强了感觉反馈的突触强度，这些增加使回路产生一种神经刺激。 在缺乏脊髓上控制的情况下稳定的运动模式。该模型将使我们能够调查上述关键假设，并对SCI后某些感觉方式被移除时获得的运动模式缺陷进行预测。将使用部分去传入或重新神经支配的肌肉（没有长度反馈的肌肉）进行实验，以测试这些预测并进一步完善模型。 该项目的目标符合国家生物医学成像和生物工程研究所的使命，即开发和加速生物医学技术的应用，并将物理和工程科学与生命科学结合起来，以推进基础研究和医疗保健。通过模型和实验研究获得的关于传入反馈在 SCI后的运动恢复可以指导脊髓损伤个体的康复训练。

Afferent feedback plays a critical role in the control of locomotion and in the recovery afforded by bodyweight supported treadmill training or grafts 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 afferent feedback in locomotor recovery have been for the most part unexplored. This multidisciplinary project will integrate a neural model of the locomotor circuitry developed at Drexel University with a biomechanical hindlimb model developed at Georgia Institute of Technology. This integrated model will be used as a test bed to study the role of afferent feedback in the control of locomotion in the intact cat and in the recovery of locomotor function after spinal transection. We hypothesize (and have demonstrated using a simplified model) that muscle length dependent feedback from the hip muscles is critical for the initiation of swing and that force feedback from the ankle extensors and cutaneous input from the footpad are critical for the control of stance. We also hypothesize that in spinal cats, training or neurotrophin producing transplants enhance the synaptic strengths of the sensory feedback and that these increases enable the circuitry to produce a stable locomotor pattern in the absence of supraspinal control. The model will allow us to investigate the above key hypotheses and make predictions about the motor pattern deficits obtained when certain sensory modalities are removed after SCI. Experiments with partially deafferented or re-innervated muscles (muscles without length feedback) will be performed to test these predictions and further refine the model. The aims of this project are consistent with the mission of the National Institute of Biomedical Imaging and Bioengineering to develop and accelerate the application of biomedical technologies and integrate the physical and engineering sciences with the life sciences to advance basic research and medical care. The insights obtained through the model and experimental studies about the roles of afferent feedback in locomotor recovery following SCI may guide rehabilitation training efforts in individuals with spinal cord injury.