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，并导致运动， 感觉和自主神经功能障碍。年，大约55%的SCI发生在宫颈水平 影响前肢的人类病人。受颈椎脊髓损伤影响的患者希望恢复手功能 和数字功能，以改善他们目前的生活方式。然而，大多数脊髓损伤 胸部损伤后功能恢复与运动功能关系的模型研究 颈部损伤后熟练的前肢图案。一般来说，熟练的前肢图案是 在间接脑干区的支持下，通过皮质脊髓束进行调节。损伤 切断皮质脊髓束显示出前肢图案的显著丧失；然而，当 保留间接通路，康复训练支持功能丧失的恢复。 我们证明这种恢复是由C3-C4固有脊髓神经元介导的，C3-C4固有脊髓神经元是一种独特的固有脊髓 神经元通常参与内部运动复制的形成，以纠正运动错误 在运动过程中。在这条通路中，错误纠正是由C3-C4PN轴突介导的 终止于小脑前核--外侧网状核的神经元。信息是 然后穿过小脑，在那里运动计划被比作本体感觉 来自前肢的信息，并返回到脑干运动控制区以供执行。我们 假设颈椎损伤后，这条通路经历了康复适应 赔偿CST的损失。在这里，我们将采取系统的方法来审问三个 这条通路的纠错和适应所需的组件。第一个目标是 检查来自几个前肢控制路径的信息集成到LRN和 如果在康复过程中调节LRN神经元的活动，则可以促进康复。第二个目标 将研究无意识本体感觉信息在康复治疗中的作用 伤势恢复。第三个目标，将研究小脑传出通路连接到 了解参与前肢运动的网状区，以确定它们在驾驶中的重要性 颈椎损伤后和康复期间的恢复和纠错。最终，这项研究 将提供必要的数据，以确定涉及技术康复的途径 脊髓损伤后的前肢模式和活动是否可以促进康复 康复训练中的依赖调节。

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.