Microglial G i-dependent dynamics regulate brain network hyperexcitability

Nat Neurosci. 2021 Jan;24(1):19-23. doi: 10.1038/s41593-020-00756-7. Epub 2020 Dec 14.

Abstract

Microglial surveillance is a key feature of brain physiology and disease. Here, we found that Gi-dependent microglial dynamics prevent neuronal network hyperexcitability. By generating MgPTX mice to genetically inhibit Gi in microglia, we show that sustained reduction of microglia brain surveillance and directed process motility induced spontaneous seizures and increased hypersynchrony after physiologically evoked neuronal activity in awake adult mice. Thus, Gi-dependent microglia dynamics may prevent hyperexcitability in neurological diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Signaling
  • Cell Movement
  • Convulsants
  • Electroencephalography
  • G-Protein-Coupled Receptor Kinase 1 / physiology*
  • Immunologic Surveillance
  • Mice
  • Microglia / enzymology
  • Microglia / physiology*
  • Microglia / ultrastructure
  • Nerve Net / physiology*
  • Nervous System Diseases / physiopathology
  • Nervous System Physiological Phenomena
  • Pilocarpine
  • Seizures / physiopathology
  • Signal Transduction
  • rho GTP-Binding Proteins / metabolism

Substances

  • Convulsants
  • Pilocarpine
  • G-Protein-Coupled Receptor Kinase 1
  • Grk1 protein, mouse
  • rho GTP-Binding Proteins