Microglia mediate forgetting via complement-dependent synaptic elimination

Synapses between engram cells are believed to be substrates for memory storage, and the weakening or loss of these synapses leads to the forgetting of related memories. We found engulfment of synaptic components by microglia in the hippocampi of healthy adult mice. Depletion of microglia or inhibition of microglial phagocytosis prevented forgetting and the dissociation of engram cells. By introducing CD55 to inhibit complement pathways, specifically in engram cells, we further demonstrated that microglia regulated forgetting in a complement- and activity-dependent manner. Additionally, microglia were involved in both neurogenesis-related and neurogenesis-unrelated memory degradation. Together, our findings…

• NN
  National Natural Science Foundation of China

  Award: 31700888
• NK
  National Key Research and Development Program of China Stem Cell and Translational Research

  Award: 2017YFA0104200
• NS
  Natural Science Foundation of Zhejiang Province

  Award: LZ19C090001