Hand use and neuronal plasticity after dorsal rhizotomy

导致手指去传入的颈背根损伤可严重损害手 功能，尤其是依赖于连续感觉反馈的手动任务的执行(即 这种损伤的外科修复很少，如果曾经的话， 成功，而灵巧的恢复通常是有限的。我们最近对成年猕猴的研究 猴子表明，在背根之后，躯体感觉通路经历了实质性的重组 损伤，这种重组有助于手功能的恢复(有时是 戏剧性的)。鉴于所有操控任务本质上都是感觉运动的，现在重要的是 对损伤的运动反应是理解的。 长期目标是：(1)确定在结构和功能上的变化 手部去传入后的感觉运动通路，有助于自发的 恢复手工灵活性，以及(2)确定可以作为目标的内生机制 从治疗上促进功能恢复。在拟议的研究中，一种独特的背根病变 将使用允许我们选择和阻止猴子离散部分的感官输入的模型 手(即拇指和食指及周围区域)。生理学和解剖学 分析将允许确定运动神经元电路的变化，这将是 在几个月的时间里与行为缺陷和手部灵活性的恢复有关。 具体目标概括如下：1.做皮质脊髓等下行皮质 运动通路有助于背根损伤后的手部自主运动吗？2。 红核-橄榄核-小脑-皮质环的连接重组对感觉丧失的反应 颈后根损伤后的输入？这种前馈系统对于自愿罚款是必要的。 手在高等灵长类动物和人类中的功能，其从手指输入的主要感觉丢失 去传入损伤后，以及3.下行皮质纤维是否形成新的功能性突触 (在背角、楔状核和红核内)，对背根损伤的反应？埃姆 我们将用分析来回答这个问题。拟议的工作将有助于提供重要的新见解 进入负责行为适应的中枢神经机制 明确的非传入性损伤。实验设计复制背侧的临床情况。 根性撕脱，由此产生的发现将更好地使开发更有效的治疗方法 适用于脊神经后根撕脱及其他神经传入和脊椎损伤的患者。

Cervical dorsal root injuries that result in the deafferentation of the fingers can severely impair hand function, especially the execution of manual tasks that depend on continuous sensory feedback (i.e. the handling and identification of objects within reach). Surgical repair of such injuries is rarely, if ever, successful, and the recovery of dexterity is typically limited. Our recent studies in the adult macaque monkey show that somatosensory pathways undergo substantial reorganization following a dorsal root lesion, and that this reorganization contributes to the recovery of hand function (which is sometimes dramatic). Given that all manipulative tasks are inherently sensorimotor, it is now important that the ¿motor¿ responses to the injury are understood. This forms the focus of the proposed investigations. The long term objectives are (1) to identify the structural and functional changes that occur in the sensorimotor pathways following deafferentation of the hand, that contribute to the spontaneous recovery of manual dexterity, and (2) to identify endogenous mechanisms that could be targeted therapeutically to promote functional recovery. In the proposed studies, a unique dorsal root lesion model will be used that allows us to select and block sensory input from a discrete part of the monkey hand (namely the thumb and index finger, and surrounding regions). Physiological and anatomical analyses will allow the determination of changes in the motor neuronal circuitry and this will be correlated with the behavioral deficit and recovery of manual dexterity over a period of several months. The specific aims in summary are as follows: 1. Do the corticospinal and other descending cortical motor pathways subserve voluntary hand movements following a dorsal root lesion? 2. Do the connections of the rubro-olivary-cerebello-cortical loop reorganize in response to the loss of sensory input following a cervical dorsal root lesion? This feedforward system is necessary to fine voluntary hand function in the higher primates and human, and its major sensory input from the digits is lost following a deafferentation injury, and 3. Do descending cortical fibers form new functional synapses (within the dorsal horn, cuneate nucleus and red nucleus), in response to a dorsal root lesion? EM analysis will be used to answer this question. The proposed work will contribute important new insight into the central neural mechanisms responsible for the behavioral adaptations that occur following a well defined deafferentation injury. The experimental design replicates the clinical condition of dorsal root avulsion, and the resulting findings will better enable the development of more effective treatments for people with avulsed spinal dorsal roots and other deafferentation and spinal injuries.