Astrocyte remodeling during the sleep/wake cycle

项目摘要 大脑是可塑性的，它的结构和功能是为了改变而建立的。结构和功能塑料 这一现象一直是人们深入研究的主题，但类似的现象是否也发生在天文学中， 细胞仍然是个谜。这种明显的知识差距的原因是，直到最近，我们 缺乏既能提供星形胶质细胞过程高分辨率图像， 以及完整的星形胶质细胞形态描述。扩张显微镜可以挑战这一点 通过提供一种令人兴奋的新方法来分析星形胶质细胞的结构和分布， 膜蛋白。总的目标是确定星形胶质细胞的形态学和 谷氨酸转运蛋白的亚细胞分布在睡眠/觉醒周期中发生变化。我们的中央卫生- 假设是星形胶质细胞过程在睡眠阶段远离兴奋性突触， 阻碍谷氨酸扩散并削弱大脑中兴奋性突触传递。我们计划测试 我们的中心假设，并达到本申请的目的，通过追求以下具体 目的：（1）确定睡眠/觉醒周期对星形胶质细胞形态的影响;（2）绘制星形胶质细胞的分子结构图。 脑星形胶质细胞谷氨酸转运体在睡眠/觉醒周期中的分布;（3）建立三维模型 谷氨酸扩散和兴奋性传递的过程。拟议研究 是重要的，因为它可能会产生关于结构变化的开创性信息， 星形胶质细胞的功能有助于神经退行性疾病的发生。拟议的研究是 创新，因为它旨在开发一个新的和全面的工具箱， 调节大脑功能的机制。最终，这些发现预计将有一个IM- 重要的积极影响，在描绘的分子和细胞机制，我们的齿轮- 在健康和疾病期间的可接受性。

PROJECT SUMMARY The brain is plastic and is built for changes in its structure and function. Structural and functional plas- ticity have been the subject of intense investigation, but whether similar phenomena occur also in astro- cytes remains enigmatic. The reason for this noticeable gap of knowledge is that until recently, we lacked microscopy approaches that can provide both a high-resolution image of astrocytic processes and a full description of the morphology of entire astrocytes. Expansion microscopy can challenge this status quo by providing an exciting new way to analyze the structure of astrocytes and the distribution of membrane proteins. The overall objective is to determine how the morphology of astrocytes and the sub-cellular distribution of glutamate transporters changes during the sleep/wake cycle. Our central hy- pothesis is that astrocytic processes move away from excitatory synapses during the sleep phase, al- tering glutamate diffusion and weakening excitatory synaptic transmission in the brain. We plan to test our central hypothesis and attain the objective of this application by pursuing the following specific aims: (1) determine the effect of the sleep/wake cycle on astrocyte morphology; (2) map the molecular distribution of glutamate transporters in astrocytes during the sleep/wake cycle; (3) develop 3D models of glutamate diffusion and excitatory transmission during the sleep/wake cycle. The proposed research is significant because it may generate groundbreaking information on how changes in the structure and function of astrocytes contribute to the onset of neurodegenerative diseases. The proposed research is innovative because it aims to develop a new and comprehensive toolbox to investigate fundamental mechanisms regulating the function of the brain. Ultimately, these findings are expected to have an im- portant positive impact in the delineation of the molecular and cellular mechanisms underlying our cog- nitive abilities during health and disease.