Synaptic plasticity: regulating synapse form & function

突触可塑性：调节突触形式

• 批准号: 6607376
• 负责人: YUKIKO GODA
• 金额: $ 5.4万
• 依托单位: MEDICAL RESEARCH COUNCIL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6607376
• 关键词: Synaptic; plasticity; regulating; synapse; form

DESCRIPTION (provided by applicant): This proposal addresses the structure-function relationship of synaptic junction: the molecular mechanisms of neurotransmitter release and morphological synaptic plasticity, and how these two processes are linked to each other. The long-term objective is to delineate the basic principles governing the stability of synaptic connectivity in central neurons, and the significance of these mechanisms to information storage and brain dysfunction underlying mental illnesses. Electrophysiological and imaging methods will be applied in dissociated hippocampal neurons grown in culture to investigate how actin-binding proteins and regulators of actin dynamics modulate release-ready synaptic vesicles, and how changes in synaptic activity, in turn, regulate presynaptic morphology. Three specific aims of the application are: (I) How do modulators of actin dynamics regulate synaptic vesicle exocytosis? We will characterize the role of modulators of actin dynamics in regulating synaptic vesicle cycle. Our working model is that modulators of actin dynamics act during vesicle docking and/or priming step to regulate the probability of neurotransmitter release. (II) How do synaptic cell adhesion molecules regulate neurotransmitter release? Contribution of the components of cell adhesion complex - integrin, cadherin and beta-catenin -in regulating synaptic vesicle exocytosis will be examined. We will test the hypothesis that cell adhesion molecules regulate synaptic transmission by modifying the dynamics of actin cytoskeleton to which they are linked intracellularly. (III) How is neuronal activity transduced to elicit changes in presynaptic morphology? We will address whether actin modulators and components of cell adhesion proteins studied in Aims I and II mediate activity-induced morphological plasticity of presynaptic actin, specifically, its redistribution to create new presynaptic structures. Our hypothesis is that synaptic cell adhesion molecules act as a signaling mechanism that transduces electrical signal into a morphological change by regulating actin dynamics.

描述（由申请人提供）：该提案解决了 突触连接的结构连接关系：分子机制 神经递质的释放和形态突触可塑性，以及如何 这两个过程相互链接。长期目标是 描述有关突触连接稳定性的基本原理 在中央神经元中，以及这些机制对信息的重要性 储存和大脑功能障碍是精神疾病的基础。电生理学 成像方法将应用于生长的分离的海马神经元 培养以研究肌动蛋白结合蛋白和肌动蛋白的调节剂如何 动力学调节可释放的突触囊泡，以及突触的变化如何 活动反过来调节突触前形态。三个特定目标 应用程序是： （i）肌动蛋白动力学调节剂如何调节突触囊泡胞吐作用？ 我们将表征肌动蛋白动力学调节剂在调节中的作用 突触囊泡周期。我们的工作模型是肌动蛋白动力学的调节器 在囊泡对接和/或启动步骤中采取行动，以调节 神经递质释放。 （ii）突触细胞粘附分子如何调节神经递质释放？ 细胞粘附复合物的成分的贡献 - 整联蛋白，钙粘蛋白 将检查调节突触囊泡胞吐作用的β -catenin -in。 我们将测试细胞粘附分子调节突触的假设 通过修改其所在的肌动蛋白细胞骨架的动力来传播 细胞内连接。 （iii）神经元活性如何转化为引起突触前的变化 形态学？我们将解决肌动蛋白调节剂和细胞的组件是否 在目标I和II中研究的粘附蛋白介导了活性诱导的 突触前肌动蛋白的形态可塑性，特别是其重新分布 创建新的突触前结构。我们的假设是突触细胞 粘附分子充当传递电气的信号传导机制 通过调节肌动蛋白动力学来向形态学变化。