SYNAPTIC ARCHITECTURE, DYNAMICS AND MECHANISM

突触结构、动力学和机制

• 批准号: 8362548
• 负责人: Michael H. B. Stowell
• 金额: $ 2.13万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362548
• 关键词: 3-Dimensional; Antibodies; Architecture; Cell physiology; Cellular Structures; Chemical Synapse; Communication; Coupled; Electrons; Elements; Enzymes; Funding; Genetic; Goals; Grant; Image; Individual; Label; Longitudinal Studies; Maps; Methods; Molecular; National Center for Research Resources; Neurons; Principal Investigator; Process; Proteins; Research; Research Infrastructure; Resources; Signaling Molecule; Source; Structure; Synapses; Synaptic Transmission; Synaptic plasticity; United States National Institutes of Health; cost; cryogenics; insight; interest; molecular assembly/self assembly; molecular dynamics; nervous system disorder; reconstruction; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Our research is focused on molecular and supramolecular structures that facilitate communication between neurons at the chemical synapse and how such structures are perturbed in neurological disease. We are particularly interested in the architectural arrangement of signaling molecules and enzymes, and characterizing the ways in which such molecular assemblies are formed and undergo changes during synaptic transmission and modulation. Our approach is to investigate individual proteins using x-ray and electron crystallographic methods and to combine this information with EM images obtained via 3-D reconstruction of supramolecular assemblies and tomographic analysis of the intact chemical synapse. Our long-term goal is to construct a dynamic molecular and architectural map for the chemical synapse that will help to understand synaptic formation, transmission and plasticity. Using electron tomographic methods we have begun to study the architecture of the chemical synapse in cultured neurons. Our first goal is to establish the common architectural elements present at the synapse and to identify the molecules involved using specific antibody labeling or genetic tagging. Subsequently, we will perform field potential stimulations coupled with cryogenic trapping to investigate the dynamic processes involved in synaptic transmission. Ultimately we plan to study long-term, stimulation dependent, synaptic changes in the hopes of gaining insight into the architectural elements underlying synaptic plasticity. FUNDING

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 我们的研究集中在分子和超分子结构上，这些结构促进了化学突触中神经元之间的通信以及这种结构如何在神经系统疾病中扰动。我们对信号分子和酶的结构排列特别感兴趣，并表征形成这种分子组件的方式并在突触传播和调制过程中发生变化。我们的方法是使用X射线和电子晶体学方法研究单个蛋白质，并将这些信息与通过超分子组件的3-D重建获得的EM图像结合在一起，以及完整化学突触的层析成像分析。我们的长期目标是为化学突触构建动态分子和建筑图，这将有助于了解突触的形成，传播和可塑性。使用电子断层扫描方法，我们已经开始研究培养神经元中化学突触的结构。我们的第一个目标是建立突触中存在的常见结构元素，并使用特定的抗体标记或遗传标记识别涉及的分子。随后，我们将执行野外电势刺激以及低温诱捕，以研究突触传播所涉及的动态过程。最终，我们计划研究长期依赖的突触变化，以了解对突触可塑性基础的建筑元素的希望。 资金