Biphasic Memory Impairment and Recovery After Sevoflurane Exposure Are Associated With Time-Dependent Hippocampal...

Dynamic modulation of α5-GABAAR expression and synaptic distribution plays a pivotal role in neuronal homeostatic plasticity, critically influencing memory processes. This study aims to investigate the spatiotemporal dynamics of α5-GABAAR in hippocampal subregions (CA1, CA3, and DG) and their behavioral correlation in mice following sevoflurane exposure across eight timepoints.

Eight-week-old female C57BL/6 mice were exposed to 3% sevoflurane for 1 h and they were subjected to trace fear conditioning followed by sevoflurane. Hippocampal tissues were harvested for proteomic analysis and immunofluorescence staining to quantify the expression of α5-GABAAR and P-gephyrin. Three-dimensional spatial colocalization of α5-GABAAR and gephyrin was reconstructed in IMARIS software.

By integrating trace fear conditioning with molecular profiling, we identified 2 days postexposure (Sev2d) as the critical phase for sevoflurane-induced memory impairment and 6 days postexposure (Sev6d) as the recovery phase. The time-dependent biphasic pattern of α5-GABAAR regulation was demonstrated by proteomics, immunofluorescence, and 3D imaging: (1) At Sev2d, α5-GABAAR expression and postsynaptic clustering were significantly elevated, which coincided with peak cognitive deficits; (2) by Sev6d, both receptor density and synaptic localization normalized to baseline level, paralleling memory restoration.

These findings indicate that changes in the expression and distribution of α5-GABAAR are correlated with sevoflurane-induced memory impairment and recovery, providing potential insights into sevoflurane-induced memory fluctuation.