Microglial TNFα controls synaptic GABAARs, slow waves and memory consolidation during sleep
bioRxiv (Cold Spring Harbor Laboratory)(2022)
摘要
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 TNFα. We demonstrate that sleep induces microglia-dependent synaptic enrichment of GABA A Rs in a manner dependent on microglial TNFα and P2RX7. We further show that microglia-specific depletion of TNFα 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 GABA A Rs, sculpt sleep slow waves and support memory consolidation.
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关键词
microglial tnfα,synaptic gaba<sub>a</sub>rs,memory consolidation,sleep
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