Background: General anesthetics depress neuronal activity. The depression and\nuncoupling of cortico-hippocampal activity may contribute to anesthetic-induced amnesia. However,\nthe molecular targets involved in this process are not fully characterized. GABAA receptors,\nespecially the type with 3 subunits, represent a main molecular target of propofol. We therefore\nhypothesized that GABAA receptors with 3 subunits mediate the propofol-induced disturbance\nof cortico-hippocampal interactions. Methods: We used local field potential (LFP) recordings\nfrom chronically implanted cortical and hippocampal electrodes in wild-type and 3(N265M)\nknock-in mice. In the 3(N265M) mice, the action of propofol via 3subunit containing GABAA\nreceptors is strongly attenuated. The analytical approach contained spectral power, phase locking,\nand mutual information analyses in the 2â??16 Hz range to investigate propofol-induced effects on\ncortico-hippocampal interactions. Results: Propofol caused a significant increase in spectral power\nbetween 14 and 16 Hz in the cortex and hippocampus of wild-type mice. This increase was absent in\nthe 3(N265M) mutant. Propofol strongly decreased phase locking of 6â??12 Hz oscillations in wild-type\nmice. This decrease was attenuated in the 3(N265M) mutant. Finally, propofol reduced the mutual\ninformation between 6â??16 Hz in wild-type mice, but only between 6 and 8 Hz in the 3(N265M)\nmutant. Conclusions: GABAA receptors containing 3 subunits contribute to frequency-specific\nperturbation of cortico-hippocampal interactions. This likely explains some of the amnestic actions\nof propofol.
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