Type-I-interferon-responsive microglia shape cortical development and behavior

Microglia are brain-resident macrophages that shape neural circuit development and are implicated in neurodevelopmental diseases. Multiple microglial transcriptional states have been defined, but their functional significance is unclear. Here, we identify a type I interferon (IFN-I)-responsive microglial state in the developing somatosensory cortex (postnatal day 5) that is actively engulfing whole neurons. This population expands during cortical remodeling induced by partial whisker deprivation. Global or microglial-specific loss of the IFN-I receptor resulted in microglia with phagolysosomal dysfunction and an accumulation of neurons with nuclear DNA damage. IFN-I gain of function increased neuronal…

• NS
  National Science Foundation

  Award: 1650113
• BW
  Burroughs Wellcome Fund
• PC
  Pew Charitable Trusts
• NI
  National Institutes of Health
• G
  Genentech
• UO
  University of California, San Francisco
• NI
  National Institute on Aging
• NI
  National Institute of Mental Health

  Awards: DP2MH116507, R01MH119349
• WI
  Weill Institute for Neurosciences, University of California, San Francisco