• Kazuhiro Uchimoto, Tomoyuki Miyazaki, Yoshinori Kamiya, Takahiro Mihara, Yukihide Koyama, Masataka Taguri, Gaku Inagawa, Takuya Takahashi, and Takahisa Goto.
• From the Department of Anesthesiology and Critical Care Medicine (K.U., T.M., Ta.M., Y.K., G.I., T.G.), Department of Physiology (T.M., T.T.), and Department of Biostatistics and Epidemiology (M.T.), Yokohama City University Graduate School of Medicine, Yokohama, Japan; and Department of Anesthesiology (Y.K.), Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
• Anesthesiology. 2014 Aug 1;121(2):302-10.

BackgroundGeneral anesthesia induces long-lasting cognitive and learning deficits. However, the underlying mechanism remains unknown. The GluA1 subunit of AMPAR is a key molecule for learning and synaptic plasticity, which requires trafficking of GluA1-containing AMPARs into the synapse.MethodsAdult male rats were exposed to 1.8% isoflurane for 2 h and subjected to an inhibitory avoidance task, which is a hippocampus-dependent contextual fear learning paradigm (n = 16 to 39). The in vitro extracellular field potential of hippocampal synapses between the Schaffer collateral and the CA1 was evaluated using a multielectrode recorder (n = 6 per group). GluA1 expression in the synaptoneurosome was assessed using Western blotting (n = 5 to 8). The ubiquitination level of GluA1 was evaluated using immunoprecipitation and Western blotting (n = 7 per group).ResultsSeven days after exposure to 1.8% isoflurane for 2 h (Iso1.8), the inhibitory avoidance learning (control vs. Iso1.8; 294 ± 34 vs. 138 ± 28, the mean ± SEM [%]; P = 0.002) and long-term potentiation (125.7 ± 6.1 vs. 105.7 ± 3.3; P < 0.001) were impaired. Iso1.8 also temporarily increased GluA1 in the synaptoneurosomes (100 ± 9.7 vs. 138.9 ± 8.9; P = 0.012) and reduced the GluA1 ubiquitination, a main degradation pathway of GluA1 (100 ± 8.7 vs. 71.1 ± 6.1; P = 0.014).ConclusionsIsoflurane impairs hippocampal learning and modulates synaptic plasticity in the postanesthetic period. Increased GluA1 may reduce synaptic capacity for additional GluA1-containing AMPARs trafficking.

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