Hand Use and Neuronal Plasticity After Dorsal Rhizotomy

描述(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纵任务的执行。这种损伤在人类发生事故和创伤后相对常见，通常很难通过手术修复。一些功能的恢复已经被证明与感觉新皮质和皮质下结构内的重组有关。这项应用是对从手向大脑提供反馈的感觉神经元受损后发生的行为、生理和结构变化的系统检查。虽然重组已经被证明，但我们对重组的神经基础、发生在哪里以及这种变化如何调节行为恢复或补偿仍然知之甚少。如果没有这方面的知识，我们就无法将现实的治疗策略对准适当的区域。 我们将使用一种独特的模型，允许我们选择和阻止来自非人类灵长类手部的独立部分--即食指和拇指及其周围区域--的感觉输入。 我们将使用生理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期间的行为缺陷和手动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.精准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，我们评估执行精确握力任务的能力。然后，我们将这种功能与病变的大小相关联，以提供手功能恢复所需的感觉反馈的指示。 2.皮层下的体感神经元群体是否有助于皮质的重新激活和手功能的恢复？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。这些信息将确定可以作为治疗目标的区域。 3.在损伤后的几个月内，初级传入是否在脊髓背角和楔状核中发芽，在楔丘脑和棘丘脑细胞上形成功能性突触？这个问题源于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，并重建在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对中枢神经机制的重要新见解，这些中枢神经机制负责在明确的背根损伤后的几个月观察到的行为适应。此外，他们还将提供对人类成年神经元背根撕脱损伤的机制的洞察，这些损伤会使人虚弱。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.