Hand Use and Neuronal Plasticity after Dorsal Rhizotomy

背神经根切断术后的手部使用和神经元可塑性

• 批准号: 8052883
• 负责人: CORINNA DARIAN-SMITH
• 金额: $ 51.51万
• 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 2013-03-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8052883
• 关键词: Accounting; Address; Adult; Affect; Animals; Area; Axon; Behavior; Behavioral; Brain; Brain Stem; Cerebellum; Cervical; Cervical nerves; Cervical spinal cord injury; Clinical; Complex; Contralateral; Corticospinal Tracts; Cutaneous; Deafferentation procedure; Development; Digit structure; Dimensions; Dorsal; Efferent Pathways; Experimental Designs; Experimental Models; Feedback; Fiber; Fingers; Future; Glycine; Goals; Grant; Hand; Hand functions; Horns; Human; Individual; Injury; Investigation; Laboratories; Lesion; Macaca; Manuals; Maps; Medial; Mediating; Modeling; Monkeys; Motor; Motor Neurons; Motor Pathways; Movement; Nature; Neuraxis; Neuronal Plasticity; Neurons; Olives - dietary; Operative Surgical Procedures; Pathway interactions; Pattern; Performance; Physiological; Plant Roots; Play; Presynaptic Terminals; Primates; Process; Public Health; Recovery; Recovery of Function; Red nucleus structure; Research; Rhizotomy procedure; Role; Sensory; Side; Simulate; Spinal; Spinal Cord; Spinal Injuries; Spinal nerve root structure; Spinal nerve structure; Structure of nucleus cuneatus; Synapses; System; Thalamic structure; Thumb structure; Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; Work; central nervous system injury; disability; dorsal horn; effective therapy; gamma-Aminobutyric Acid; grasp; gray matter; indexing; insight; nerve injury; neuromechanism; neuronal circuitry; postsynaptic; public health relevance; repaired; response; response to injury; sensory feedback; somatosensory; spinal nerve posterior root

DESCRIPTION (provided by applicant): 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 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 and ventral 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 simulates aspects of the clinical condition of spinal root avulsion, and makes the study of the mechanistic changes in a complex system possible. The resulting findings will inform our understanding of the changes that occur in clinical injuries, and better enable the future development of effective treatments for people with avulsed root and other spinal and central nervous system injuries. PUBLIC HEALTH RELEVANCE Cervical spinal nerve injuries can result in a severe and permanent loss of hand function which is rarely repaired successfully by surgery. This disability can be accurately reproduced in the monkey in a controlled experimental model, which enables the analysis of the reorganized brain in the months following injury. Our current and proposed studies focus on examining factors that impede or promote the recovery of hand function, and our findings will enable the development of more effective treatments of cervical nerve and spinal injury

描述（由申请人提供）：导致手指传入神经阻滞的颈背根损伤会严重损害手部功能，尤其是依赖于连续感觉反馈的手动任务的执行（即处理和识别可达范围内的物体）。此类损伤的手术修复很少成功，而且灵活性的恢复通常也很有限。我们对成年猕猴的研究表明，背根病变后体感通路会发生实质性重组，并且这种重组有助于手功能的恢复（有时是戏剧性的）。鉴于所有操作任务本质上都是感觉运动，因此现在了解对损伤的“运动”反应非常重要。这构成了拟议调查的重点。长期目标是（1）确定手部传入神经阻滞后感觉运动通路中发生的结构和功能变化，这些变化有助于手动灵活性的自发恢复；（2）确定可以作为治疗目标以促进功能恢复的内源性机制。在拟议的研究中，将使用独特的背根病变模型，使我们能够选择和阻止来自猴手离散部分（即拇指和食指以及周围区域）的感觉输入。生理学和解剖学分析将允许确定运动神经元回路的变化，这将与几个月内的行为缺陷和手动灵活性的恢复相关。具体目标概括如下： 1. 皮质脊髓和其他皮质下降运动通路是否有助于背根病变后的手部自主运动？ 2. 颈椎背根病变后感觉输入丧失，红橄榄-小脑-皮质环路的连接是否会重组？这种前馈系统对于改善高等灵长类动物和人类的随意手部功能是必要的，并且其来自手指的主要感觉输入在传入神经阻滞损伤后丢失，以及 3. 下降皮质纤维是否会形成新的功能性突触（在背角和腹角、楔形核和红核内），以应对背根病变？电磁分析将用于回答这个问题。拟议的工作将为对负责明确定义的传入神经阻滞损伤后发生的行为适应的中枢神经机制提供重要的新见解。实验设计模拟了脊柱根部撕脱的临床状况，使得研究复杂系统的机械变化成为可能。由此产生的结果将有助于我们了解临床损伤发生的变化，并更好地为未来开发针对根部撕脱伤和其他脊柱和中枢神经系统损伤的有效治疗方法。公共卫生相关性 颈椎神经损伤可导致手部功能严重且永久性丧失，而这种情况很少能通过手术成功修复。这种残疾可以在受控实验模型中在猴子身上准确地重现，从而能够在受伤后的几个月内对重组的大脑进行分析。我们当前和拟议的研究重点是检查阻碍或促进手功能恢复的因素，我们的研究结果将有助于开发出更有效的颈神经和脊髓损伤治疗方法