Synaptic Function: Effects of the Nerve Injury, Repair, and Altered Activity

突触功能：神经损伤、修复和活动改变的影响

基本信息

批准号：
9001373
负责人：
Timothy C Cope
金额：
$ 75.87万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-16 至 2018-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9001373
关键词：
Address Adult Advisory Committees Affect Axon Axotomy Behavior Books Collaborations Conflict (Psychology)Core Facility Electrophysiology (science)Ensure Feedback Funding Goals Health Injury Knowledge Label Learning Light Limb structure Manuals Methods Military Personnel Modification Motor Motor Neurons Movement Muscle Muscle Spindles Natural regeneration Nature Nerve Nerve Regeneration Nervous System Trauma Nervous system structure Neuraxis Neuromuscular Junction Neurons Operative Surgical Procedures Outcome Pathway interactions Peripheral Peripheral Nerves Peripheral nerve injury Procedures Property Radial Nerve Lesions Recovery Recovery of Function Research Research Personnel Research Project Grants Rest Sensorimotor functions Sensory Signal Transduction Spinal Spinal Cord Spinal cord injury Stroke Structure of ulnar nerve Synapses Techniques Testing Time Traumatic injury United States Viral War Work cellular imaging design functional outcomes improved improved outcome in vivo injury and repair insight interest limb movement median nerve monosynaptic reflex motor control nerve injury neurotransmission novel peripheral nerve transection prevent programs public health relevance receptor reinnervation repaired response sensory discrimination synaptic function therapy development tissue processing vesicular release

项目摘要

DESCRIPTION (provided by applicant): We designed this program project to coordinate synergistic research efforts around the central theme that nerve regeneration is not synonymous with functional recovery. We are uniquely focused on changes occurring in the sensorimotor motor circuits that are responsible for coordinating muscle activity and purposeful limb movement. In the aftermath of peripheral nerve transection and regeneration, spinal circuits do not regain normal feedback about movement from the centrally-projecting axon branches of either primary afferents or motoneurons. In the previous funding period, we discovered that these centrally- projecting axons and their spinal connections are permanently lost or altered, even when peripheral axon branches successfully reconnect with appropriate targets. Three projects, each led by an established investigator who brings unique experimental expertise and conceptual insight to the program, will advance our knowledge of the response of spinal circuits to peripheral nerve injury and regeneration. Project 1 will apply electrophysiological methods in vivo to test a proposed treatment to improve outcome following peripheral nerve injury. Project 2 will use a novel viral retrograde labeling technique to ask questions about circuit reorganization that have previously been impossible to address. Together, Projects 1 and 2 will test the hypothesis that circuit changes in the spinal cord triggered by peripheral nerve injury are more global than the monosynaptic reflex. The results will shed light on the nature of the changes that explain the modification in motor control and behavior after injury. Project 3 will define the pathway that underlies in vivo signaling that occurs via spontaneous vesicle release at the neuromuscular junction and will determine whether this pathway also signals synaptic stripping from motoneurons following peripheral nerve injury. All three projects will be assisted by the Cellular Imaging, Surgery and Tissue Processing Core Facility (Core B). This core provides the support and expertise necessary to ensure consistency and quality of procedures for all three PPG research projects. An external advisory committee reviewing our program project in 2010 concluded, "this is an unusually interactive group with significant intellectual interactions evidet in many of the projects." It is our hope that continued close collaboration between projects, will bring significant added value as we move towards development of therapy to promote recovery following nerve injury. Public Health Relevance: Our overarching goal is to improve recovery following injury to the nervous system. Our specific focus is recovery of spinal cord motor function following peripheral nerve injury. Because similar cellular and synaptic changes might also operate as consequence of central nervous injuries, this work will also inform efforts to promote recovery from nervous system injuries after insults such as stroke and spinal cord injury. Disclaimer: The critiques and criterion scores from individual reviewers are provided below in an essentially unedited form. These were prepared prior to the review meeting and may not have been updated or revised subsequent to the discussion at the meeting. Therefore, they may not fully reflect the final opinions of the individual reviewers at the close of group discussion o the final majority opinion of the group. The Resume and Summary of Discussion above summarizes the final outcome of the group discussion. OVERALL PROGRAM EVALUATION

描述（由申请人提供）：我们设计了该程序项目，以协调围绕中心主题的协同研究工作，即神经再生不是功能恢复的代名词。我们独特地专注于在感觉运动电路中发生的变化，这些变化负责协调肌肉活动和有目的的肢体运动。在周围神经横向和再生之后，脊柱回路不会从主要传入剂或运动神经元的中央注射轴突分支中恢复有关运动的正常反馈。在上一个融资期间，我们发现这些集中投射轴突及其脊柱连接被永久丢失或改变，即使外围轴突分支成功地与适当的靶标重新连接。三个项目由一位既定的研究者领导，他们将独特的实验专业知识和概念性见解带给该计划，这将促进我们对脊柱回应对外围神经损伤和再生的反应的了解。项目1将在体内应用电生理方法来测试拟议的治疗方法，以改善周围神经损伤后的预后。项目2将使用一种新型的病毒逆行标签技术来询问有关电路重组的问题，这些问题以前无法解决。总之，项目1和2将检验以下假设：周围神经损伤触发的脊髓的电路变化比单突触反射更全球。结果将阐明变化的性质，这些变化解释了受伤后运动控制和行为的修改。项目3将定义通过神经肌肉连接处自发囊泡释放发生的体内信号传导的途径，并将确定该途径是否还信号在周围神经损伤后从运动神经元中发出突触剥离。这三个项目将通过细胞成像，手术和组织加工核心设施（Core B）的帮助。该核心提供了必要的支持和专业知识，以确保所有三个PPG研究项目的一致性和程序质量。一个审查我们计划项目的外部咨询委员会在2010年得出结论：“这是一个异常互动的群体，在许多项目中具有重要的智力互动。”我们希望，随着我们朝着开发治疗以促进神经损伤后的康复，将持续密切合作，将带来巨大的增值。公共卫生相关性：我们的总体目标是改善神经系统受伤后的恢复。我们的具体重点是外周神经损伤后脊髓运动功能的恢复。由于类似的细胞和突触变化也可能是由于中枢神经损伤而作用的，因此这项工作还将为促进侮辱和脊髓损伤等侮辱后的神经系统损伤康复而努力。免责声明：以下基本未经编辑的形式提供了个人审阅者的批评和标准分数。这些是在审查会议之前准备的，可能在会议上的讨论之后未进行更新或修订。因此，在小组讨论结束时，他们可能无法完全反映单个审阅者的最终意见。上面的讨论简历和摘要总结了小组讨论的最终结果。总体计划评估