| First Author | Socodato R | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 12 | Pages | 113447 |
| PubMed ID | 37980559 | Mgi Jnum | J:343500 |
| Mgi Id | MGI:7567252 | Doi | 10.1016/j.celrep.2023.113447 |
| Citation | Socodato R, et al. (2023) Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance. Cell Rep 42(12):113447 |
| abstractText | Microglia, the largest population of brain immune cells, continuously interact with synapses to maintain brain homeostasis. In this study, we use conditional cell-specific gene targeting in mice with multi-omics approaches and demonstrate that the RhoGTPase Rac1 is an essential requirement for microglia to sense and interpret the brain microenvironment. This is crucial for microglia-synapse crosstalk that drives experience-dependent plasticity, a fundamental brain property impaired in several neuropsychiatric disorders. Phosphoproteomics profiling detects a large modulation of RhoGTPase signaling, predominantly of Rac1, in microglia of mice exposed to an environmental enrichment protocol known to induce experience-dependent brain plasticity and cognitive performance. Ablation of microglial Rac1 affects pathways involved in microglia-synapse communication, disrupts experience-dependent synaptic remodeling, and blocks the gains in learning, memory, and sociability induced by environmental enrichment. Our results reveal microglial Rac1 as a central regulator of pathways involved in the microglia-synapse crosstalk required for experience-dependent synaptic plasticity and cognitive performance. |
