Astrocyte remodeling during the sleep/wake cycle

项目总结 大脑是可塑性的，是为其结构和功能的变化而构建的。结构和功能平台- 丰度一直是密集调查的主题，但类似的现象是否也发生在天文领域。 细胞仍然是个谜。造成这种明显的知识差距的原因是，直到最近，我们 缺乏能够提供星形细胞过程的高分辨率图像的显微镜方法 以及对整个星形胶质细胞形态的完整描述。扩张显微镜可以挑战这一点 为分析星形胶质细胞的结构和分布提供了一种令人兴奋的新方法 膜蛋白。总体目标是确定星形胶质细胞的形态和 谷氨酸转运体的亚细胞分布在睡眠/清醒周期中发生变化。我们的中央- 假说是，在睡眠阶段，星形细胞突起远离兴奋性突触。 抑制谷氨酸扩散，削弱脑内兴奋性突触传递。我们计划测试 我们的中心假设，并通过追求以下具体目标来实现此应用程序的目标 目的：(1)确定睡眠/清醒周期对星形胶质细胞形态的影响；(2)绘制分子图谱 睡眠/清醒周期中星形胶质细胞谷氨酸转运体的分布；(3)建立三维模型 谷氨酸在睡眠/清醒周期中的扩散和兴奋性传递。拟议的研究 意义重大，因为它可能会产生有关结构和结构如何变化的开创性信息 星形胶质细胞的功能与神经退行性疾病的发生有关。拟议的研究是 创新，因为它的目标是开发一个新的、全面的工具箱来研究基本 调节大脑功能的机制。最终，这些发现预计将产生影响-- 在描述我们的COG的分子和细胞机制方面产生了重要的积极影响- 在健康和疾病期间的学习能力。

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.