AbstractBackground 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 Postoperative memory impairment in aged mice was associated with deficits in memory consolidation, characterised by a reduced SPW-R frequency and duration in the CA1 region. Induction of SPW-Rs had the potential to improve memory consolidation (from 34.3 9.4 to 53.1 18.7%, P=0.016). Additionally, we observed a decrease in the number of c-Fos-positive pyramidal neurones in the CA3 region following surgery, which contributed to diminished excitatory transmission to the CA1 region. Activating CA3 pyramidal neurones through chemogenetic approaches restored activity in CA1 pyramidal neurones, ameliorating SPW-R disruption (frequency from 0.20 0.05 to 0.25 0.15 events s−1, 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.
Wu et al. (Fri,) studied this question.