Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance
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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.
Original language | English |
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Article number | 113447 |
Journal | Cell Reports |
Volume | 42 |
Issue number | 12 |
Number of pages | 28 |
ISSN | 2211-1247 |
DOIs | |
Publication status | Published - 2023 |
Bibliographical note
Publisher Copyright:
© 2023 The Authors
- cognition, CP: Cell biology, CP: Neuroscience, environmental enrichment, glia-neuron interactions, microglia, proteomics, Rac1, RhoGTPases, RNAseq, synaptic plasticity
Research areas
ID: 374454604