Hand use and neuronal plasticity after dorsal rhizotomy

颈椎背根损伤导致手指的传入神经阻滞会严重损害手的功能 功能，特别是依赖于连续感觉反馈的手动任务的执行（即 在可及范围内的物体的处理和识别）。手术修复这种损伤是很少的，如果有的话， 成功，并且灵巧性的恢复通常是有限的。我们最近对成年猕猴的研究 猴子显示，躯体感觉通路经历了实质性的重组后，背根 损伤，并且这种重组有助于手功能的恢复（这有时是 戏剧性）。考虑到所有的操纵任务都是固有的感觉运动，现在重要的是， 对损伤的运动反应是可以理解的。这是拟议调查的重点。 长期目标是：（1）确定发生在 感觉运动通路后的手，这有助于自发的 恢复手的灵活性，和（2）以确定内源性机制，可以针对 以促进功能恢复。在拟议的研究中，一个独特的背根病变， 我们将使用一个模型，它允许我们选择和阻止来自猴子一个离散部分的感觉输入 手（即拇指和食指，以及周围区域）。生理和解剖 分析将允许确定运动神经元回路中的变化， 在几个月的时间里，与行为缺陷和手部灵活性的恢复相关。 具体目标概括如下：1.皮质脊髓和其他下行皮质 背根损伤后，运动通路有助于手的自主运动？2.做 红核-橄榄-小脑-皮质环的连接对感觉神经元的丧失作出反应， 颈椎背根损伤后的输入？这种前馈系统是必要的罚款自愿 高等灵长类动物和人类的手功能，其主要的感官输入从手指丢失 在去传入神经损伤之后，以及3.下行皮质纤维形成新的功能性突触吗 （在背角，楔状核和红核），在响应背根损伤？EM 分析将被用来回答这个问题。拟议的工作将有助于重要的新见解 进入负责行为适应的中枢神经机制， 明确的传入神经阻滞损伤。实验设计复制了背部的临床条件， 根撕脱，由此产生的发现将更好地促进更有效的治疗方法的发展 用于脊髓背根撕脱和其他传入神经阻滞和脊髓损伤的患者。

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.