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

ABSTRACT: 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. Phosphoproteomics profiling detected a large modulation of RhoGTPase signaling, predominantly of Rac1, in microglia of mice exposed to an environmental enrichment protocol. Ablation of microglial Rac1 affected pathways involved in microglia-synapse communication, disrupted experience-dependent synaptic remodeling, and blocked the gains in learning, memory and sociability induced by environmental enrichment.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Tiago Almeida

LAB HEAD: João Bettencourt Relvas

PROVIDER: PXD045719 | Pride | 2023-10-23

REPOSITORIES: Pride

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

Project description: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.

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