Towards a molecular and systemic characterization of synaptogenesis and synaptic function

突触发生和突触功能的分子和系统表征

• 批准号: 61273261
• 负责人: Professorin Dr. Daniela C. Dieterich
• 金额: --
• 依托单位: Institut für Pharmakologie und Toxikologie
• 依托单位国家: 德国
• 项目类别: Independent Junior Research Groups
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/61273261?language=en
• 关键词: Towards; molecular; systemic; characterization; synaptogenesis

Upon completion of brain development neurons and glia form a high-performance communication network courtesy of trillions of specialized contact sites. Synaptogenesis, the formation of new synaptic contacts, and long-lasting forms of synaptic plasticity, which are believed to be the molecular substrate for learning and memory, require the synthesis of new proteins and the correct localization of these proteins within the neuron at active synaptic sites. Despite considerable efforts and the characterization of multiple synaptic proteins, a comprehensive and dynamic characterization of the synaptic proteome during synaptogenesis and synaptic plasticity is still missing. Moreover, the role of glia during neuronal development and processes of synaptic plasticity as well as the identity of the glial proteome are largely unknown. I herein aim to attain a molecular and systemic characterization of both the neuronal and glial proteomes at different stages of development of the hippocampal formation of the rat using the two recently developed techniques BONCAT and FUNCAT. These tools enable the time-resolved dynamic identification and in situ visualization of the subpopulation of newly synthesized, endogenous proteins. This work will deepen our understanding of the molecular and systemic aspects of synaptogenesis, synaptic plasticity and the neuron-glia partnership.

大脑发育完成后，神经元和神经胶质细胞形成一个由数万亿个专门接触位点提供的高性能通信网络。突触发生、新突触接触的形成以及持久形式的突触可塑性被认为是学习和记忆的分子底物，需要新蛋白质的合成以及这些蛋白质在神经元内活跃突触位点的正确定位。尽管付出了相当大的努力并对多种突触蛋白进行了表征，但仍然缺乏突触发生和突触可塑性过程中突触蛋白质组的全面和动态表征。此外，神经胶质细胞在神经元发育和突触可塑性过程中的作用以及神经胶质蛋白质组的身份在很大程度上尚不清楚。我在此的目的是使用最近开发的两种技术 BONCAT 和 FUNCAT 来获得大鼠海马结构不同发育阶段的神经元和神经胶质蛋白质组的分子和系统特征。这些工具能够对新合成的内源蛋白质亚群进行时间分辨动态识别和原位可视化。这项工作将加深我们对突触发生、突触可塑性和神经元-胶质细胞伙伴关系的分子和系统方面的理解。