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

  • Br J Anaesth. 2026 Jul;137(1):154-167. doi: 10.1016/j.bja.2026.03.019.
Jiangnan Wu  1 ,  Xu Wang  1 ,  Wei Li  1 ,  Wei Sun  1 ,  Hao Feng  2 ,  Zunsai Feng  1 ,  Ziqing Xu  1 ,  Zhun Wang  3 ,  Gongming Wang  4 ,  Mengyuan Zhang  5
Affiliations
  • 1. Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
  • 2. Department of Anesthesiology, The Second Qilu Hospital of Shandong University, Jinan, China.
  • 3. Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
  • 4. Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. Electronic address: [email protected].
  • 5. Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. Electronic address: [email protected].
PMID: 42091343 DOI: 10.1016/j.bja.2026.03.019
Abstract

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: 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.

Keywords
memory consolidation; microglial activation; neural circuit; postoperative memory impairment; sharp-wave ripples.
Products