Microglial TNFα controls GABAAR plasticity, slow waves and memory consolidation during sleep
Pinto, M. J.; Bizien, L.; Fabre, J. M.; Thukanovic, N.; Lepetz, V.; Henderson, F.; Pujol, M.; Sala, R. W.; Tarpin, T.; Popa, D.; Triller, A.; Lena, C.; Fabre, V.; Bessis, A.
Show 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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