Reprogramming the Outputs of Spinal Circuits

重新编程脊髓电路的输出

• 批准号: 7698303
• 负责人: Arthur W. English
• 金额: $ 32.94万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7698303
• 关键词: Address; Afferent Neurons; Area; Axon; Biological Assay; Biological Models; Boxing; Chronic; Clinical; Conditioned Reflex; Disease; Effectiveness; Electric Stimulation; Electromyography; Elements; Exercise; Goals; Gray unit of radiation dose; Growth; Injury; Intervention; Locomotion; Measures; Motor; Motor Neurons; Movement; Muscle; Muscle function; Musculoskeletal; Musculoskeletal System; Natural regeneration; Nerve; Neurons; Operant Conditioning; Operative Surgical Procedures; Outcome; Output; Pathway interactions; Patients; Pattern; Peripheral; Peripheral Nerves; Peripheral nerve injury; Plastics; Population; Process; Protocols documentation; Rattus; Recovery; Recovery of Function; Rehabilitation therapy; Science; Sensory; Shapes; Specificity; Spinal; Spinal Cord; Stimulus; Text; Time; Training; abstracting; ankle joint; axon regeneration; base; conditioning; design; functional outcomes; improved; injured; injury and repair; innovation; kinematics; nerve supply; neural circuit; reinnervation; repaired; research study; response; restoration; sciatic nerve; sensory feedback; spinal reflex

Abstract When a peripheral nerve is injured, the relationship between the musculoskeletal system and the neural circuits in the spinal cord which regulate movement is lost. Axons in the proximal stump of the cut nerve can regenerate and can reinnervate peripheral targets, but muscles are often reinnervated by different motoneurons than before the injury. Using different paradigms which will enhance the early regeneration of axons in cut nerves exacerbates this loss of topographic specificity. Over time, there is little evidence for remodeling of this innervation pattern. This new relationship between spinal circuits and the musculoskeletal system is a major contributor to the poor functional outcomes observed clinically. One potential strategy for improving functional recovery might be to induce adaptive changes in the spinal circuits themselves, such that an improved functional relationship of their outputs to the pattern of reinnervation of the musculoskeletal system might be achieved. In this project, we will investigate the capacity to induce such adaptive changes.. Using transection and surgical repair of the rat sciatic nerve, with and without enhancement of early axon regeneration, as a model system, we will study the capacity of the outputs of spinal circuits to adapt spontaneously over time by analyzing the timing of activity of antagonist muscles and ankle joint kinematics during different forms of treadmill locomotion. In addition, two innovative approaches to modifying the outputs of spinal circuits will be studied. First, we will examine the effect of treadmill exercise during the reinnervation period on the extent to which different reinnervated muscular targets are activated at functionally appropriate times. By activating motoneurons through spinal circuits during treadmill locomotion at a time that regenerating motor and sensory axons are growing and reforming connections with muscles, one might anticipate either that the original reinnervation of muscles might be more precise than found without exercise, that the outputs of the spinal circuits will change in an adaptive manner during the reinnervation process, or both. Second, we will investigate whether operant conditioning of spinal reflexes can be used to modify the outputs of spinal circuits. After muscles have been reinnervated, spinal reflexes will be shaped to produce functionally appropriate responses using such conditioning. The effectiveness of this training on the timing of antagonist muscles during treadmill locomotion will be evaluated. It is anticipated that the results of these studies will provide a science base not only for improved rehabilitation treatment of a large population of patients with peripheral nerve injuries but also the treatment of other disorders in which the relationship between spinal circuits and the musculoskeletal system has been disrupted and then re-established.

抽象的 当周围神经受伤时，肌肉骨骼系统与 脊髓中调节运动的神经回路丢失。近端树桩的轴突 切开的神经可以再生并可以重新弥补外围靶标，但肌肉通常是 与受伤前不同的运动神经元增强。使用不同的范式 增强切割神经中轴突的早期再生加剧了地形特异性的丧失。 随着时间的流逝，几乎没有证据表明这种神经支配模式的重塑。这种新的关系 脊柱回路和肌肉骨骼系统之间是功能不佳的主要因素 结局在临床上观察到。改善功能恢复的一种潜在策略可能是 诱导脊柱回路本身的适应性变化，从而提高功能 他们的产量与肌肉骨骼系统的加重模式的关系可能是 成就了。在这个项目中，我们将调查诱导这种适应性变化的能力。 大鼠坐骨神经的横向和手术修复，没有早期轴突的增强 再生，作为模型系统，我们将研究脊柱回路的产能的能力 随着时间的流逝，通过分析拮抗剂肌肉和踝关节活动的时间来自发。 在不同形式的跑步机运动中的运动学。此外，两种创新的方法 将研究修改脊柱电路的输出。首先，我们将检查跑步机的效果 在重新支配期内运动在不同的肌肉靶标的程度上 在功能适当的时间激活。通过通过脊柱电路激活运动神经元 在再生电动机和感觉轴突正在增长并且 改革与肌肉的联系，人们可能会预料到原始的连接 肌肉可能比没有运动的肌肉更精确，脊柱电路的输出将 在重新支配过程中或两者兼有自适应方式。第二，我们将调查 是否可以使用脊柱反射的操作调节来修改脊柱电路的输出。 肌肉加剧后，脊柱反射将形成以便在功能上产生 使用这种调节的适当回应。这项培训对时间安排的有效性 将评估跑步机上的拮抗剂肌肉。预计的结果 这些研究将不仅为改善大型康复治疗提供科学基础 周围神经损伤的患者人群，但也治疗其他疾病 脊柱回路与肌肉骨骼系统之间的关系已被破坏，然后 重新建立。