bioRxivNeurosciencePreprint
Microglial TNFα controls GABAAR plasticity, sleep slow waves and memory consolidation
Maria J. PintoiD, Lucy BizieniD, Julie MJ FabreiD, Nina Ðukanović, Valentin Lepetz, Fiona HendersoniD, Marine PujoliD, Romain W SalaiD, Thibault TarpiniD, Daniela PopaiD, Antoine TrilleriD, Clément LénaiD, Véronique FabreiD, Alain BessisiD
Abstract
Microglia sense the changes in their environment. How microglia actively translate these changes into suitable cues to adapt brain physiology is unknown. We reveal an activity-dependent regulation of cortical inhibitory synapses by microglia, driven by purinergic signaling acting on P2RX7 and mediated by microglia-derived TNF. We demonstrate that sleep induces microglia-dependent synaptic enrichment of GABAARs in a manner dependent on microglial TNF and P2RX7. We further show that microglia-specific depletion of TNF alters slow waves during NREM sleep and blunt memory consolidation in sleep-dependent learning tasks. Together, our results reveal that microglia orchestrate sleep-intrinsic plasticity of synaptic GABAARs, sculpt sleep slow waves and support memory consolidation.
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