Hand Use and Neuronal Plasticity After Dorsal Rhizotomy

描述（由申请人提供）：人类和其他灵长类动物的颈后根损伤会严重损害手的功能-特别是依赖感觉反馈的操作任务的表现。这种损伤在人类事故和创伤后相对常见，并且通常难以手术修复。一些功能的恢复已经被证明与感觉新皮层和皮层下结构的重组有关。这个应用程序是一个系统的检查行为，生理和结构的变化，发生损伤后的感觉神经元，提供反馈，从手到大脑。虽然重组已经被证明，我们仍然知道相对较少的神经基础，它发生在哪里，以及这些变化如何介导行为恢复或补偿。如果没有这些知识，我们就无法将现实的治疗策略瞄准适当的区域。 我们将使用一个独特的模型，使我们能够选择和阻止来自非人类灵长类动物手的离散部分的感觉输入-即食指和拇指及其周围区域。 我们将使用生理学和解剖学分析来确定躯体感觉神经元回路的变化，并将这些结果与几个月内的行为缺陷和手部灵活性的恢复相关联。 具体目标是相互依存的，可以用以下问题来概括。 1.精确握力的自发恢复与背根节段的范围有何关系？在几个月的时间里，我们评估执行精确抓握任务的能力。然后，我们将这个功能与病变的大小相关联，以提供手部功能恢复所需的感觉反馈的指示。 2.皮层下体感神经元群是否有助于皮层激活和手功能恢复？我们将评估神经轴不同水平的电生理变化，以确定功能重组集中在哪里。该信息将识别治疗可以靶向的区域。 3.在损伤后的几个月内，“发芽”进入脊髓背角和楔核的初级传入神经在楔丘脑和脊髓丘脑细胞上形成功能性突触吗？这个问题来自一项初步研究的结果。我们将使用神经解剖学和超微结构技术来直接识别功能性突触，并重建背根损伤后发生的初级传入回路的变化。 拟议的研究将有助于重要的新的见解负责的行为适应，在几个月内观察到一个明确的背根损伤后的中枢神经机制。此外，他们将提供深入了解成人神经元背根撕脱损伤的机制，在人类这是衰弱。如果要更有效地治疗脊髓背根撕脱患者，则需要更好地了解损伤后躯体感觉通路的重组。

DESCRIPTION (provided by applicant): Injuries of the cervical dorsal roots in humans and other primates can severely impair hand function - particularly the performance of manipulative tasks that depend on sensory feedback. Such injuries are relatively common following accidents and trauma in humans, and are typically difficult to repair surgically. Some recovery of function has been demonstrated that has been linked to reorganization within the sensory neocortex and subcortical structures. This application is a systematic examination of behavioral, physiological and structural changes that occur following damage to the sensory neurons that supply feedback from the hand to the brain. Although reorganization has been demonstrated, we still know relatively little about the neural basis for it, where it occurs, and how such changes mediate behavioral recovery or compensation. Without this knowledge we cannot target realistic therapeutic strategies to the appropriate regions. We will use a unique model that allows us to select and block sensory input from a discrete part of the non-human primate hand- namely the index finger and thumb and surrounding regions. We will use physiological and anatomical analyses to determine changes in the somatosensory neuronal circuitry and correlate these results with the behavioral deficit and recovery of manual dexterity over a period of several months. The specific aims are inter-dependent, and can be summarized by the following questions. 1. How does the spontaneous recovery of precision grip relate to the extent of the dorsal root section? Over a period of several months we evaluate the ability to perform a precision grip task. We will then correlate this function with the size of the lesion to provide an indication of the sensory feedback required for some recovery of hand function. 2. Do subcortical somatosensory neuron populations contribute to cortical reactivation and recovery of hand function? We will evaluate electrophysiological changes at different levels of the neuraxis to identify where functional reorganization is concentrated. This information will identify regions where therapy could be targeted. 3. Do primary afferents that 'sprout' into the spinal dorsal horn and cuneate nucleus during the post-lesion months form functional synapses on cuneothalamic and spinothalamic cells? This question arises from the results of a preliminary study. We will use neuroanatomical and ultrastructural techniques to directly identify functional synapses and to reconstruct changes in the primary afferent circuitry that occur following the dorsal root lesion. The proposed studies will contribute important new insight into the central neural mechanisms responsible for the behavioral adaptations that are observed during the months following a well defined dorsal root injury. In addition they will provide insight into the mechanisms of adult neuronal dorsal root avulsion injuries in humans which are debilitating. A better understanding of the post-lesion reorganization of the somatosensory pathways is needed if patients with avulsed spinal dorsal roots are to be treated more effectively.