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: 7625323
• 负责人: CORINNA DARIAN-SMITH
• 金额: $ 50万
• 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: 2004-04-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7625323
• 关键词: Accounting; Address; Adult; Affect; Animals; Area; Axon; Behavior; Behavioral; Brain Stem; Cerebellum; Cervical; Chromosome Pairing; Clinical; Condition; Contralateral; Corticospinal Tracts; Cutaneous; Deafferentation procedure; Development; Digit structure; Dimensions; Dorsal; Efferent Pathways; Experimental Designs; Feedback; Fiber; Fingers; Glycine; Goals; Grant; Hand; Hand functions; 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; Play; Presynaptic Terminals; Primates; Process; Progress Reports; Recovery; Recovery of Function; Red nucleus structure; Rhizotomy procedure; Role; Role playing therapy; Sensory; Side; Spinal; Spinal Cord; Spinal Injuries; Structure of nucleus cuneatus; Synapses; System; Thalamic structure; Thumb structure; Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; Work; dorsal horn; gamma-Aminobutyric Acid; grasp; gray matter; indexing; insight; neuromechanism; neuronal circuitry; postsynaptic; repaired; response; response to injury; sensory feedback; somatosensory; spinal nerve posterior root

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.

颈椎背根损伤导致手指传入神经阻滞，严重损害手部 功能，尤其是依赖于连续感官反馈的手动任务的执行（即 处理和识别触手可及的物体）。此类损伤很少（如果有的话）进行手术修复 成功，但灵活性的恢复通常是有限的。我们最近对成年猕猴的研究 猴子表明，体感通路在背根后经历了实质性的重组 病变，并且这种重组有助于手功能的恢复（有时 戏剧性）。鉴于所有的操作任务本质上都是感觉运动，现在重要的是 对损伤的“运动”反应是可以理解的。这构成了拟议调查的重点。 长期目标是 (1) 确定发生在结构和功能上的变化 手传入神经阻滞后的感觉运动通路，有助于自发性 恢复手的灵活性，以及​​（2）确定可以针对的内源机制 治疗上促进功能恢复。在拟议的研究中，独特的背根病变 我们将使用模型来选择和阻止来自猴子离散部分的感官输入 手（即拇指和食指及其周围区域）。生理和解剖学 分析将允许确定运动神经元电路的变化，这将是 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. 做皮质脊髓和其他降皮质 运动通路促进背根病变后的手部自主运动？ 2. 执行以下操作 红橄榄-小脑-皮质环路的连接因感觉丧失而重组 颈椎背根病变后的输入？该前馈系统对于罚款自愿性是必要的 高等灵长类动物和人类的手部功能，并且来自手指的主要感觉输入丢失 传入神经阻滞损伤后，以及 3. 下降皮质纤维是否会形成新的功能性突触 （在背角、楔形核和红核内），对背根病变的反应？ EM 将通过分析来回答这个问题。拟议的工作将提供重要的新见解 进入负责随后发生的行为适应的中枢神经机制 明确的传入神经阻滞损伤。实验设计复制了背侧的临床状况 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开发 适用于脊髓背根撕脱以及其他传入神经阻滞和脊柱损伤的患者。