SPINAL PLASTICITY OF A CORRECTIVE KINEMATIC RESPONSE

脊髓完全横断（ST）后哺乳动物脊髓的运动学习表明，在缺乏脊髓上输入的情况下，神经元的可塑性水平显着。例如，ST猫和大鼠可以学习执行运动任务，如踏步和站立。此外，脊髓可以感知，响应，并成功地学习克服扰动的步骤周期。脊髓内这些复杂决策事件背后的神经机制尚不清楚。这个建议的中心假设是，哺乳动物的腰髓有能力正常化的运动学的后肢在一个步骤周期的摆动阶段的扰动，这些适应性事件介导的分子机制类似于那些与大脑中的学习。脊髓产生纠正运动学反应的能力将使用本实验室开发的机器人系统进行检查，该系统将在步进周期期间施加编程扰动，然后量化运动学反应。拟议的实验将表征运动和生理适应摆动相力场诱导的学习ST大鼠的腰髓。选择性的神经基板和特定的通路与适应性反应将使用药理学，解剖学和生物化学方法进行检查，以深入了解这些学习和记忆事件可以归因于生理和分子机制。将使用蛋白质印迹和免疫组织化学在逆行鉴定的执行运动控制的屈肌和伸肌运动池中测量磷酸化环AMP结合元件蛋白。腰椎间盘突出症中信号通路的生化适应 cord将与使用蛋白质合成抑制剂的反应的剂量依赖性抑制相关。这些研究将使我们开始，以确定生理和细胞事件，可能是脊髓运动学习的基础，并提供了一个框架，在人类患者神经损伤后，使用依赖性治疗程序的策略可以开发。显然，为了促进脊髓损伤或中风后运动功能的恢复，以运动学正确的模式训练运动任务行为是重要的。了解运动学习发生的生理和细胞机制， 更好地了解控制姿势和运动的脊髓神经通路如何受到使用依赖性机制的影响。

Motor learning in the mammalian spinal cord following a complete spinal cord transection (ST) suggests a remarkable level of neuronal plasticity in the absence of supraspinal input. For example, ST cats and rats can learn to perform motor tasks such as stepping and standing. Furthermore, the spinal cord can sense, respond to, and successfully learn to overcome a perturbation to the step cycle. The neural mechanisms that underlie these complex decision-making events within the spinal cord are unknown. The central hypothesis of this proposal is that the mammalian lumbar spinal cord has the capability to normalize the kinematics of the hindlimbs in response to a perturbation in the swing phase of a step cycle, and that these adaptive events are mediated by molecular mechanisms similar to those associated with learning in the brain. The ability of the spinal cord to generate a corrective kinematic response will be examined using a robotic system developed in this laboratory, which will impose a programmed perturbation during the step cycle and then to quantify the kinematic response. The proposed experiments will characterize the kinematic and physiological adaptations to swing phase force field induced learning by the lumbar spinal cord in ST rats. Selective neural substrates and specific pathways associated with the adaptive responses will be examined using pharmacological, anatomical and biochemical approaches to gain insight into the physiological and molecular mechanisms to which these learning and memory events can be attributed. Phosphorylated cyclic AMP binding element protein will be measured using Western blots and immunohistochemistry in retrogradely identified flexor and extensor motor pools that execute kinematic control. Biochemical adaptations in the signaling pathways in the lumbar spinal cord will be correlated with dose dependent inhibition of the response using protein synthesis inhibitors. These studies will allow us to begin to identify physiological and cellular events that may underlie spinal motor learning, and provide a framework around which strategies for use-dependent therapeutic procedures following neural injury in human patients can be developed. It is apparent that in order to facilitate recovery of motor function after spinal cord injury or stroke, it is important to train the motor task behavior in a kinematically correct pattern. Understanding the physiological and cellular mechanisms by which motor learning occurs will provide a better understanding of how spinal neural pathways that control posture and locomotion are influenced by use-dependent mechanisms.