Microglial TNFα controls daily changes in synaptic GABAARs and sleep slow waves.
Animals
Microglia
/ metabolism
Tumor Necrosis Factor-alpha
/ metabolism
Synapses
/ metabolism
Mice
Receptors, GABA-A
/ metabolism
Mice, Inbred C57BL
Sleep, Slow-Wave
Male
Receptors, Purinergic P2X7
/ metabolism
Neuronal Plasticity
/ physiology
Sleep
/ physiology
Memory Consolidation
Signal Transduction
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
01 Jul 2024
01 Jul 2024
Historique:
received:
19
01
2024
revised:
18
03
2024
accepted:
28
03
2024
medline:
2
5
2024
pubmed:
2
5
2024
entrez:
2
5
2024
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 38695719
pii: 276724
doi: 10.1083/jcb.202401041
pii:
doi:
Substances chimiques
Tumor Necrosis Factor-alpha
0
Receptors, GABA-A
0
Receptors, Purinergic P2X7
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : European Research Council
ID : 322821
Pays : International
Informations de copyright
© 2024 Pinto et al.