Microglial Rac1 is essential for experience-dependent brain plasticity and cognitive performance.
Cell Rep
; 42(12): 113447, 2023 12 26.
Article
en En
| MEDLINE
| ID: mdl-37980559
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neuropéptidos
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Encéfalo
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Cognición
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Microglía
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Proteína de Unión al GTP rac1
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Plasticidad Neuronal
Límite:
Animals
Idioma:
En
Revista:
Cell Rep
Año:
2023
Tipo del documento:
Article