Slowing of the hippocampal θ rhythm correlates with anesthetic-induced amnesia.
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.
Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. mperouansky@wisc.edu
Misha
M
Perouansky
Vinuta
V
Rau
Tim
T
Ford
S Irene
SI
Oh
Mark
M
Perkins
Edmond I
EI
Eger
Robert A
RA
Pearce
D020324:Amnesia, Anterograde / Q000139:chemically induced* / Q000523:psychology; D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003627:Data Interpretation, Statistical; D004567:Electrodes, Implanted; D005239:Fear / Q000187:drug effects; D006221:Halothane / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D007530:Isoflurane / Q000494:pharmacology; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D009609:Nitrous Oxide / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000187:drug effects; D012044:Regression Analysis; D013826:Theta Rhythm / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D018079:Receptors, GABA; D007530:Isoflurane; D009609:Nitrous Oxide; D006221:Halothane