Hand Use and Neuronal Plasticity After Dorsal Rhizotomy

背神经根切断术后手的使用和神经元可塑性

• 批准号: 6946925
• 负责人: CORINNA DARIAN-SMITH
• 金额: $ 34.7万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6946925
• 关键词: Macaca; afferent nerve; cell population study; cell proliferation; cholera toxin; dorsal root; electrophysiology; functional ability; hand; laboratory rat; nerve injury; neural plasticity; neuroanatomy; neuronal guidance; sensory feedback; synapses

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.

描述（由申请人提供）：人类和其他灵长类动物颈背根损伤可严重损害手功能-特别是依赖于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，通常难以通过手术修复。一些功能的恢复已被证明与感觉新皮层和皮层下结构的重组有关。该应用系统地检查了从手到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。虽然重组已经被证实，但我们对它的神经基础，它发生的地方，以及这些变化如何调节行为恢复或补偿，仍然知之甚少。没有这些知识，我们就无法针对适当的区域制定现实的治疗策略。