LOSS AND RESTORATION OF FUNCTION AFTER NEURONAL INJURY

神经元损伤后功能的丧失和恢复

• 批准号: 6393770
• 负责人: Kenneth J Muller
• 金额: $ 23.17万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-06-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6393770
• 关键词: Hirudinea; axon reaction; behavior test; behavioral /social science research tag; behavioral habituation /sensitization; confocal scanning microscopy; electron microscopy; functional ability; immunocytochemistry; interneurons; nerve injury; nervous system regeneration; neural conduction; neural initiation; neural plasticity; serotonin; synaptogenesis

DESCRIPTION (Adapted from applicant's abstract): A major problem of neuroscience is to understand the mechanisms of behavioral recovery following neural injury. Findings from our laboratories during the present project of non-associative learning by nerve regeneration and suggest new mechanisms of non-associative learning. Thus we propose to use the leech as a model system that study the cellular basis of functional recovery following injury. This entirely collaborative work is the basis for the proposed cellular, and behavioral studies on recovery of the capacity of one form of learning, sensitization, following damage to central circuits. The project represents the convergence of our separate behavioral and synapse regeneration studies in the leech, combining in depth work on modulation of defensive shortening from one laboratory and work on sensory neurons and on the 5 interneuron, its connections and its responses to injury from the other laboratory. The proposed experiments will provide insight into the questions: (1) What cellular changes underlie learning, including non-associative learning, and (2) by what cellular mechanisms does the nervous system recovery from injury? The leech is particularly advantageous for studies of this type because its ganglia contain identifiable neurons capable of regenerating specific connections following axotomy, because individual neurons can be selectively ablated or their axons cut without injury to surrounding structures, and because stereotyped adult behaviors can be examined both in vivo and in vitro while recording from identified neurons, including the S cell. The proposed experiments will determine (1) the mechanism increasing S cell activity during sensitization of reflexive shortening, including the relative roles of serotonin, relief of conduction block and reflection of impulses in mechanosensory neurons; (2) how signals are conveyed from the sensitizing stimulus, especially involving the S cell; (3) the mechanism by which sensitization is restored following repair of the S cell axon and its synapse properties of S cell connections in relation to nitric oxide synthase (NOS) activity. We shall focus on sensitization, which is eliminated by S cell ablation, rather than on dishabituation, which is only impaired. The methodology will include electrophysiological recording, intracellular injection of morphological markers, laser microbeam axotomy, behavioral testing of leeches including semi-intact preparation, immunocytochemistry, and confocal and electron microscopy. The proposed studies will reveal cellular circuitry for non-associative learning and basic mechanisms for restoration of plastic properties of the nervous system following injury.

描述（根据申请人的摘要改编）： 神经科学是了解行为恢复的机制 神经损伤。目前我们实验室的发现 通过神经再生进行非缔合学习的项目，并建议新的 非社交学习的机制。因此，我们建议使用水ech 作为研究功能恢复细胞基础的模型系统 受伤后。这项完全协作的工作是 拟议的蜂窝细胞和有关恢复能力的行为研究 在中央电路损坏后，一种学习，敏化的形式。 该项目代表了我们单独的行为和 在水ech中的突触再生研究，结合了深度工作 调节一个实验室的防御性缩短和感官工作 神经元和5个中间神经元，其连接及其对 另一个实验室受伤。提出的实验将提供 深入了解问题：（1）哪些细胞变化是学习的基础， 包括非缔合学习，（2）通过哪种细胞机制 神经系统会从受伤中恢复吗？水ech特别是 对于这种类型的研究有利，因为其神经节包含 能够再生特定连接的可识别神经元 轴切开后，因为可以选择性地消融单个神经元 或它们的轴突切割而没有受伤的结构，因为 可以在体内和体外检查刻板的成人行为 从鉴定神经元（包括S细胞）记录的同时。这 提出的实验将确定（1）增加S细胞的机制 反射缩短的敏化期间的活动，包括 5-羟色胺的相对作用，缓解传导阻滞和反射 机械感觉神经元的冲动； （2）信号如何从 敏感刺激，尤其是涉及S细胞的刺激； （3）机制 修复S轴突和 它与一氧化氮有关的S细胞连接的突触特性 合酶（NOS）活性。我们将专注于敏化，这是 通过S细胞消融消除，而不是在不清楚的情况下消除 只有受损。该方法将包括电生理学 记录，形态学标记的细胞内注射，激光 微束轴切开术，包括半独立性在内的水ech的行为测试 制备，免疫细胞化学以及共聚焦和电子显微镜。 拟议的研究将揭示非缔合性的细胞回路 恢复塑料特性的学习和基本机制 受伤后神经系统。