Adaptation of internal motor copy circuits in recovery after spinal cord injury.

摘要： 脊髓损伤（SCI）每年影响大约100，000名患者， 感觉和自主神经功能障碍。大约55%的SCI发生在宫颈水平， 影响前肢的人类患者。受颈椎脊髓损伤影响的患者希望恢复手部功能 和数字功能来改善他们目前的生活方式。然而，大多数脊髓损伤 模型研究了胸部损伤后与运动相关的功能恢复， 颈部受伤后熟练的前肢模式。一般来说，熟练的前肢模式是 在间接脑干区域的支持下通过皮质脊髓束介导。病变 切断皮质脊髓束的人显示出前肢模式的显著丧失;然而，当 间接通路得以保留，康复训练有助于恢复失去的功能。 我们发现这种恢复是由C3-C4脊髓本体神经元介导的，这是一种独特的脊髓本体神经元。 一种神经元，通常参与形成内部运动复制以纠正运动错误 在运动中。在该通路中，错误纠正由C3-C4 PN轴突介导 终止于外侧网状核（小脑前核）的神经元。信息 然后通过小脑，将运动计划与本体感觉进行比较 信息从前肢和回到脑干运动控制区执行。我们 假设在颈部损伤后，该通路经历康复适应， 补偿CST的损失。在这里，我们将采取系统的方法来询问三个 错误纠正和适应这一途径所需的组件。第一个目标将 检查来自几个前肢控制通路的信息整合到LRN中， 如果在康复过程中调节LRN神经元活动增强恢复。第二个目的 将研究无意识的本体感觉信息在康复中的作用。 恢复受伤。第三个目标，将研究小脑传出通路连接到 了解涉及前肢运动的网状区域，以确定其在驾驶中的重要性 颈椎损伤后和康复期间的恢复和错误纠正。最终，这项研究 将提供必要的数据，以确定参与康复恢复的途径， 脊髓损伤后的前肢模式，如果恢复可以通过活动增强 康复训练中的依赖性调节。

Abstract: Spinal cord injuries (SCI) affect approximately 100,000 patients each year and causes motor, sensory and autonomic dysfunction. Approximately 55% of all SCIs occur at the cervical level in human patients that effect forelimb. Patients effected by a cervical SCI desire recovery of hand and digit function to improve their current lifestyle. However, the majority of spinal cord injury models study the functional recovery associates with locomotion after thoracic lesions and not skilled forelimb patterning after cervical injuries. In general, skilled forelimb patterning is mediated through the corticospinal tract with support from indirect brainstem regions. Lesions that cut the corticospinal tract show significant loss of forelimb patterning; however, when the indirect pathways are preserved, rehabilitative training supports the recovery of the lost function. We show that this recovery is mediated by C3-C4 propriospinal neurons, a unique propriospinal neuron normally involved in the formation of an internal motor copy to correct movement errors during the movement. In this pathway, error correction is mediated by C3-C4 PN axons terminating onto neurons in the lateral reticular nucleus, a pre-cerebellar nucleus. Information is then routed through the cerebellum where the motor plan is compared to proprioceptive sensory information from the forelimb and back to brainstem motor control regions for execution. We hypothesize that after cervical injury this pathway undergoes rehabilitative adaptation to compensate for loss of the CST. Here we will take a systems approach to interrogate three components required for error correction and adaptation of this pathway. The first aim will examine the integration of information from several forelimb control pathways into the LRN and if modulation of LRN neuronal activity during rehabilitation augments recovery. The second aim will investigate the role of unconscious proprioceptive sensory information in rehabilitative recovery of injury. The third aim, will investigate the cerebellar efferent pathways connecting to know reticular regions involved in forelimb movements to determine their importance in driving recovery and error correction after cervical injury and during rehabilitation. Ultimately, this study will provide essential data to identify the pathways involved in rehabilitative recovery of skilled forelimb patterning after spinal cord injury and if recovery can be enhanced by activity dependent modulation during rehabilitative training.