Towards a molecular and systemic characterization of synaptogenesis and synaptic function

在大脑发育完成后，神经元和神经胶质细胞形成了一个高性能的通信网络，这要归功于数万亿个专门的联系地点。突触发生、新突触接触的形成和突触可塑性的持久形式被认为是学习和记忆的分子底物，需要合成新的蛋白质，并在神经元内的活跃突触位置正确定位这些蛋白质。尽管对多种突触蛋白进行了大量的研究和鉴定，但对突触发生和突触可塑性过程中的突触蛋白质组的全面和动态的描述仍然是空白。此外，胶质细胞在神经元发育和突触可塑性过程中的作用以及胶质蛋白质组的身份在很大程度上是未知的。在此，我的目标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性蛋白质的亚群进行时间分辨的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。

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.