Sevoflurane-induced amnesia is associated with inhibition of hippocampal cell ensemble activity after learning

General anesthesia could induce amnesia, however the mechanism remains unclear. We hypothesized that suppression of neuronal ensemble activity in the hippocampus by anesthesia during the post-learning period causes retrograde amnesia. To test this hypothesis, two experiments were conducted with sevoflurane anesthesia (2.5%, 30 min): a hippocampus-dependent memory task, the context pre-exposure facilitation effect (CPFE) procedure to measure memory function and in vivo calcium imaging to observe neural activity in hippocampal CA1 during context exploration and sevoflurane/home cage session. Sevoflurane treatment just after context pre-exposure session impaired the CPFE memory, suggesting sevoflurane induced retrograde amnesia. Calcium imaging showed sevoflurane treatment prevented neuronal activity in CA1. Further analysis of neuronal activity with non-negative matrix factorization, which extracts neural ensemble activity based on synchronous activity, showed that sevoflurane treatment reduced the reactivation of neuronal ensembles between during context exploration just before and one day after sevoflurane inhalation. These results suggest that sevoflurane treatment immediately after learning induces amnesia, resulting from suppression of reactivation of neuronal ensembles.