Microglial activation disrupts hippocampal CA1 sharp-wave ripples via the CA3–CA1 neural circuit that contributes to postoperative memory consolidation deficits in aged mice

BACKGROUND: Memory impairment is a common postoperative neurological complication among elderly patients. Sharp-wave ripples (SPW-Rs) in the CA1 region of the hippocampus play a critical role in memory consolidation. However, the extent to which disruptions in CA1 SPW-Rs contribute to postoperative memory impairment remains poorly understood. METHODS: An 18-month-old male C57BL/6J mice were exposed to 3 vol% sevoflurane combined with laparotomy. Various methodologies, including context fear conditioning, local field potential monitoring, immunofluorescence staining, viral tracing, optogenetics, and chemogenetics, were used to elucidate the involvement of SPW-Rs in the CA1 region in postoperative memory impairment in aged mice. RESULTS: , P=0.018; duration from 0.034 [0.0028] to 0.039 [0.0033] s, P=0.014) and memory impairment. Microglial activation was associated with SPW-R disruption and postoperative memory deficits. CONCLUSIONS: Surgery triggers microglial activation, leading to the release of neuroinflammatory factors that inhibit hippocampal CA3 pyramidal neurone activation, ultimately disrupting SPW-R dynamics and impairing memory consolidation.