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Updated: Jun 27, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglial TNFα controls daily changes in synaptic GABAARs and sleep slow waves
Maria Joana Pinto1, Lucy Bizien1, Julie M J Fabre1
1Institut de Biologie de l'École Normale Supérieure (IBENS), École Normale Supérieure, CNRS, INSERM, Université PSL, Paris, France.
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 GABAARs 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 GABAARs, sculpt sleep slow waves, and support memory consolidation.
Insights
Microglia regulate brain function during sleep by influencing inhibitory synapses. This process, involving purinergic signaling and TNFα, is crucial for memory consolidation.
Area of Science:
- Neuroscience
- Cell Biology
- Sleep Science
Background:
- Microglia are immune cells in the brain that respond to environmental changes.
- The mechanisms by which microglia adapt brain physiology are not fully understood.
Purpose of the Study:
- To investigate the role of microglia in regulating cortical inhibitory synapses during sleep.
- To elucidate the molecular pathways involved in microglia-mediated synaptic plasticity.
Main Methods:
- Activity-dependent regulation of cortical inhibitory synapses by microglia.
- Investigated purinergic signaling via P2RX7 and microglia-derived TNFα.
- Examined sleep-induced synaptic enrichment of GABAARs.
Main Results:
- Microglia regulate inhibitory synapses via purinergic signaling (P2RX7) and TNFα.
- Sleep promotes GABAAR enrichment at synapses, dependent on microglial TNFα and P2RX7.
- Depletion of microglial TNFα impairs slow waves during NREM sleep and memory consolidation.
Conclusions:
- Microglia orchestrate sleep-intrinsic plasticity of synaptic GABAARs.
- Microglia play a key role in sculpting sleep slow waves.
- Microglial functions are essential for memory consolidation during sleep.
