Related Experiment Video
Updated: May 8, 2026
Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology
Published on: March 23, 2011
Microglial activation disrupts hippocampal CA1 sharp-wave ripples via the CA3-CA1 neural circuit that contributes to
Jiangnan Wu1, Xu Wang1, Wei Li1
1Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
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.
Insights
Surgery impairs memory in aged mice by disrupting hippocampal sharp-wave ripples (SPW-Rs). Activating CA3 neurons rescues SPW-R function and improves memory consolidation, highlighting a potential therapeutic target.
Area of Science:
- Neuroscience
- Gerontology
- Anesthesiology
Background:
- Postoperative memory impairment is a common neurological complication in elderly patients.
- Sharp-wave ripples (SPW-Rs) in the hippocampus are crucial for memory consolidation.
- The precise role of CA1 SPW-R disruptions in postoperative memory deficits is not well understood.
Purpose of the Study:
- To investigate the contribution of CA1 sharp-wave ripples (SPW-Rs) to postoperative memory impairment in aged mice.
- To explore the underlying mechanisms involving hippocampal neuronal activity and neuroinflammation.
Main Methods:
- Aged mice underwent sevoflurane anesthesia and surgery.
- Behavioral tests (context fear conditioning) assessed memory.
- Electrophysiology monitored local field potentials.
- Immunofluorescence, viral tracing, optogenetics, and chemogenetics were employed to study neuronal activity and connectivity.
Main Results:
- Postoperative memory deficits correlated with reduced CA1 SPW-R frequency and duration.
- Inducing SPW-Rs improved memory consolidation.
- Surgery decreased CA3 pyramidal neuron activity, impacting CA1 excitatory transmission.
- Chemogenetic activation of CA3 neurons restored CA1 activity, ameliorated SPW-R disruption, and rescued memory impairment.
- Microglial activation was linked to SPW-R disruption and memory deficits.
Conclusions:
- Surgery-induced microglial activation releases neuroinflammatory factors.
- These factors inhibit hippocampal CA3 pyramidal neuron activation.
- This inhibition disrupts SPW-R dynamics, impairing memory consolidation.
- Targeting CA3 neuron activation presents a potential strategy to mitigate postoperative memory impairment.
