Slowing of the hippocampal theta rhythm correlates with anesthetic-induced amnesia.

摘要

BACKGROUND: Temporary, antegrade amnesia is one of the core desirable endpoints of general anesthesia. Multiple lines of evidence support a role for the hippocampal theta rhythm, a synchronized rhythmic oscillation of field potentials at 4-12 Hz, in memory formation. Previous studies have revealed a disruption of the theta rhythm at surgical levels of anesthesia. We hypothesized that theta-rhythm modulation would also occur at subhypnotic but amnestic concentrations. Therefore, we examined the effect of three inhaled agents on properties of the theta rhythm considered critical for the formation of hippocampus-dependent memories. METHODS: We studied the effects of halothane and nitrous oxide, two agents known to modulate different molecular targets (GABAergic [gamma-aminobutyric acid] vs. non-GABAergic, respectively) and isoflurane (GABAergic and non-GABAergic targets) on fear-conditioned learning and theta oscillations in freely behaving rats. RESULTS: All three anesthetics slowed theta peak frequency in proportion to their inhibition of fear conditioning (by 1, 0.7, and 0.5 Hz for 0.32% isoflurane, 60% N2O, and 0.24% halothane, respectively). Anesthetics inconsistently affected other characteristics of theta oscillations. CONCLUSIONS: At subhypnotic amnestic concentrations, theta-oscillation frequency was the parameter most consistently affected by these three anesthetics. These results are consistent with the hypothesis that modulation of the theta rhythm contributes to anesthetic-induced amnesia.