TY - JOUR T1 - Microglia remodel the synaptic signaling required for context-dependent cognitive performance JF - bioRxiv DO - 10.1101/2021.10.18.464802 SP - 2021.10.18.464802 AU - Renato Socodato AU - Tiago O. Almeida AU - Camila C. Portugal AU - Evelyn C. S. Santos AU - Joana Tedim-Moreira AU - Teresa Canedo AU - Filipa I. Baptista AU - Ana Magalhães AU - António F. Ambrósio AU - Cord Brakebusch AU - Boris Rubinstein AU - Irina Moreira AU - Teresa Summavielle AU - Inês Mendes Pinto AU - João B. Relvas Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/10/19/2021.10.18.464802.abstract N2 - Microglia modulate synaptic activity, essential for context-dependent cognitive performance, allowing organism-level adaptations to different environmental scenarios. Yet, the microglial molecular drivers required for synaptic remodeling related to cognitive performance remain largely elusive. Here, combining conditional gene targeting, single-cell live imaging, RNA-seq, high-throughput proteomics, systems biology, and animal behavior, we mapped a molecular nexus between microglia and synapses that instructs cognitive performance. Specifically, we found that microglia use the RhoGTPase Rac1 as a relay switch to sense the brain microenvironment and drive synaptic remodeling required for experience-dependent sociability and learning related to memory. Targeting this microglial relay modifies context-dependent cognitive performance.Competing Interest StatementThe authors have declared no competing interest. ER -