3-DIMENSIONAL STRUCTURE AND FUNCTION OF SYNAPSES

该项目旨在通过对突触前、突触后和神经胶质元素的结构、连通性和可塑性的定量和三维分析，了解发育和成熟大脑中突触的结构和功能。这些知识对于了解突触在学习和记忆等正常大脑功能中的作用，以及损伤和疾病对这些功能的影响非常重要。信息学的目标是改进定量分析的方法，并在网上获得超微结构教程和解剖数据，这也与神经科学的目标具有重要的相关性。神经科学的其他目标是在正在进行的关于突触发生、长时程增强(LTP)和长时程增强(LTD)的研究项目中使用新的信息学工具，这是学习和记忆的两个最重要的突触模型。具体目标是：1)改进脑连续切片的获取、配准、分割和三维重建。2)加强公共领域的软件，即可上网和第三方可扩展的软件，以支持数据库的开发和神经科学研究。3)扩大我们的突触和突触周围解剖学的互联网可访问库，作为一个社区资源，将分子连接到神经元层面的分析。4)使用新的重建工具确定阻断突触传递对成年大鼠海马片的棘突、突触及其相关的星形胶质细胞突起结构的影响。5)使用新的重建工具来确定在LTP和LTD期间，未成熟或成熟的海马神经元的突触数量、突触大小或对接的突触前小泡的数量是否以相反的方向调节。此外，使用新的工具来评估局部蛋白质合成(由多聚核糖体表示)或膜循环(由内糖体表示)是否介导了经历LTP或LTD的突触的结构变化。

This project is directed at understanding the structure and function of synapses in the developing and mature brain, by quantitative and three-dimensional analysis of the structure, connectivity, and plasticity of presynaptic, postsynaptic, and glial elements. Such knowledge is important for understanding the role of synapses in normal brain functions such as learning and memory, and the effects of injury and disease on these functions. The informatics objective is to improve the methods of quantitative analysis and availability of ultrastructural tutorials and anatomical data on the web, which has significant relevance for the neuroscience objectives as well. Additional neuroscience objectives are to use the new informatics tools in ongoing research projects on synaptogenesis, long-term potentiation (LTP), and long-term depression (LTD), which are two of the most important synaptic models of learning and memory. The specific aims are: 1) Improve the acquisition, alignment, segmentation, and 3D reconstruction of serial sections from brain. 2) Enhance software for the public domain, that is internet-accessible and third-party extensible to support development of the database and neuroscience research. 3) Expand our internet-accessible repository of synaptic and perisynaptic anatomy that serves as a community resource for connecting the molecular to the neuron levels of analyses. 4) Use the new reconstruction tools to determine the impact of blocking synaptic transmission on the structure of spines, synapses and their associated astroglial processes in adult rat hippocampal slices. 5) Use the new reconstruction tools to determine whether synapse number, synaptic size, or the number of docked presynaptic vesicles are regulated in opposite directions during LTP and LTD at immature or mature hippocampal neurons. In addition, use the new tools to evaluate whether local protein synthesis, indicated by polyribosomes, or membrane recycling, indicated by endosomes, mediate the structural changes at synapses that have undergone LTP or LTD.