Activity Patterns in the Prefrontal Cortex and Hippocampus during and after Awakening from Etomidate Anesthesia

Background: The anesthetic properties of etomidate are largely mediated by gamma-aminobutyric acid type A receptors. There is evidence for the existence of gamma-aminobutyric acid type A receptor subtypes in the brain, which respond to small concentrations of etomidate. After awakening from anesthesia, these subtypes are expected to cause cognitive dysfunction for a yet unknown period of time. The corresponding patterns of brain electrical activity and the molecular identity of gamma-aminobutyric acid type A receptors contributing to these actions remain to be elucidated. Methods: Anesthesia was induced in wild-type and beta 3(N265M) knock-in mice by intravenous injection of 10 mg/kg etomidate. Local field potentials were recorded simultaneously in the prefrontal cortex and hippocampus using chronically implanted electrode arrays. Local field potentials were sampled before, during, and after anesthesia. Results: In the prefrontal cortex and hippocampus of wildtype mice, intravenous bolus injection of etomidate evoked isoelectric baselines and subsequent burst suppression. These effects were largely attenuated by the beta 3(N265M) mutation. During emergence from anesthesia, power density in the theta band (5-15 Hz) transiently increased in the hippocampus of wild types, but not in the mutants, indicating that this actionwas caused by the receptors harboring beta 3 subunits. In both genotypes, etomidate produced a long-lasting (> 1 h after recovery of righting reflexes) decrease in theta-peak frequency. Significant slowing of theta activity was apparent in the hippocampus and prefrontal cortex. Conclusions: Etomidate-induced patterns of brain activity during deep anesthesia mostly involve actions at beta 3 containing gamma-aminobutyric acid type A receptors. During the post-anesthesia period, altered theta-band activity indicates ongoing anesthetic action.