Slowing of the hippocampal θ rhythm correlates with anesthetic-induced amnesia

Anesthesiology. 2010 Dec;113(6):1299-309. doi: 10.1097/ALN.0b013e3181f90ccc.


Background: Temporary, antegrade amnesia is one of the core desirable endpoints of general anesthesia. Multiple lines of evidence support a role for the hippocampal θ rhythm, a synchronized rhythmic oscillation of field potentials at 4-12 Hz, in memory formation. Previous studies have revealed a disruption of the θ rhythm at surgical levels of anesthesia. We hypothesized that θ-rhythm modulation would also occur at subhypnotic but amnestic concentrations. Therefore, we examined the effect of three inhaled agents on properties of the θ 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 [γ-aminobutyric acid] vs. non-GABAergic, respectively) and isoflurane (GABAergic and non-GABAergic targets) on fear-conditioned learning and θ oscillations in freely behaving rats.

Results: All three anesthetics slowed θ 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 θ oscillations.

Conclusions: At subhypnotic amnestic concentrations, θ-oscillation frequency was the parameter most consistently affected by these three anesthetics. These results are consistent with the hypothesis that modulation of the θ rhythm contributes to anesthetic-induced amnesia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amnesia, Anterograde / chemically induced*
  • Amnesia, Anterograde / psychology
  • Anesthesia*
  • Anesthetics, Inhalation / pharmacology
  • Animals
  • Behavior, Animal / drug effects
  • Data Interpretation, Statistical
  • Electrodes, Implanted
  • Fear / drug effects
  • Halothane / pharmacology
  • Hippocampus / drug effects*
  • Isoflurane / pharmacology
  • Learning / drug effects
  • Male
  • Memory / drug effects
  • Nitrous Oxide / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA / drug effects
  • Regression Analysis
  • Theta Rhythm / drug effects*


  • Anesthetics, Inhalation
  • Receptors, GABA
  • Isoflurane
  • Nitrous Oxide
  • Halothane