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

• 批准号: 9195825
• 负责人: Timothy C Cope
• 金额: $ 76.23万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 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/9195825
• 关键词: Synaptic; Function; Effects; Nerve; Injury

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.

描述（由申请人提供）：我们设计这个项目是为了协调围绕神经再生并不等同于功能恢复这一中心主题的协同研究工作。我们特别关注负责协调肌肉活动和有目的的肢体运动的感觉运动运动回路中发生的变化。在周围神经横断和再生之后，脊髓回路不会重新获得关于来自初级传入神经或运动神经元的中央突出轴突分支的运动的正常反馈。在之前的资助期间，我们发现这些中心突出的轴突及其脊柱连接永久丢失或改变，即使外围轴突分支成功地与适当的目标重新连接。三个项目均由一位知名研究人员领导，他为该项目带来了独特的实验专业知识和概念见解，将增进我们对脊髓回路对周围神经损伤和再生的反应的了解。项目 1 将应用体内电生理学方法来测试拟议的治疗方法，以改善周围神经损伤后的结果。项目 2 将使用一种新颖的病毒逆行标记技术来提出以前无法解决的有关电路重组的问题。项目 1 和项目 2 将共同检验以下假设：周围神经损伤引发的脊髓回路变化比单突触反射更为全面。研究结果将揭示变化的本质，从而解释受伤后运动控制和行为的改变。项目 3 将定义通过神经肌肉接头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也发出周围神经损伤后运动神经元突触剥离的信号。所有三个项目都将得到细胞成像、手术和组织处理核心设施（核心 B）的协助。该核心提供必要的支持和专业知识，以确保所有三个 PPG 研究项目程序的一致性和质量。 2010 年审查我们项目的外部咨询委员会得出的结论是：“这是一个异常互动的团队，在许多项目中都有明显的智力互动。”我们希望，随着我们开发促进神经损伤后恢复的治疗方法，项目之间持续密切的合作将为我们带来显着的附加值。