Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance. Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance

Microglia, the largest population of brain immune cells, continuously interact with synapses to maintain brain homeostasis. We aimed at understanding the role of Rac1 on microglia functions. Here, we used conditional cell-specific gene targeting in mice with multi-omics approaches, and demonstrated that the RhoGTPase Rac1 was an essential requirement for the microglia to sense and interpret the brain microenvironment, and for crucial microglia-synapse crosstalk driving experience-dependent plasticity, a fundamental brain property impaired in several neuropsychiatric disorders. Overall design: Microglia were isolated by MACS (CD11b+ cells) from 3 Rac1fl/fl (CT) and 3 Cx3cr1CreER+/:Rac1fl/fl (Rac1 cKO) and total RNA was extracted. Sequencing was performed on an Ion Torrent S5XL sequencerTM (Thermo Scientific)

小胶质细胞（Microglia）是脑内数量最多的免疫细胞，可通过持续与突触相互作用维持脑内稳态。本研究旨在探究Rac1在小胶质细胞功能中的作用。本研究采用小鼠条件性细胞特异性基因靶向技术结合多组学方法，证实RhoGTP酶（RhoGTPase）Rac1是小胶质细胞感知、解读脑微环境的必要条件，同时也是驱动经验依赖性可塑性的关键小胶质细胞-突触串扰所必需的；而经验依赖性可塑性作为一项核心脑特性，在多种神经精神疾病中均存在受损情况。
实验设计：从3只Rac1fl/fl（对照组，CT）小鼠与3只Cx3cr1CreER+/Rac1fl/fl（Rac1条件性敲除，Rac1 cKO）小鼠中，通过磁珠分选（MACS）分离CD11b+细胞以获取小胶质细胞，随后提取总RNA，并在Ion Torrent S5XL测序仪（赛默飞世尔科技，Thermo Scientific）上完成测序。