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A Metabolic Mechanism for Anaesthetic Suppression of Cortical Synaptic Function in Mouse Brain Slices—A Pilot Investigation

Propofol Affects Cortico-Hippocampal Interactions via β3 Subunit-Containing GABAA Receptors

Department of Anesthesiology and Intensive Care, Klinikum rechts der Isar, Technical University of Munich, School of Medicine, Munich, Ismaninger Str. 22, 81675 München, Germany
Werner Reichardt Centre for Integrative Neuroscience, Eberhard-Karls-University, Otfried-Müller-Str. 25, 72076 Tübingen, Germany
Department of Anesthesiology, Neuroanesthesia Division, Columbia University Medical Center, New York Presbyterian Hospital, 622 West 168th Street, New York City, NY 10032, USA
Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL 61802-6178, USA
Carl R. Woese Institute for Genomic Biology, University of Illiniois at Urbana-Champaign, Urbana, IL 61801, USA
Department of Anaesthesiology, Experimental Anaesthesiology Section, Eberhard-Karls-University, Waldhörnlestrasse 22, 72072 Tübingen, Germany
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(16), 5844;
Received: 22 July 2020 / Revised: 5 August 2020 / Accepted: 7 August 2020 / Published: 14 August 2020
(This article belongs to the Special Issue Molecular Mechanisms and Neural Correlates of General Anesthesia)
Background: General anesthetics depress neuronal activity. The depression and uncoupling of cortico-hippocampal activity may contribute to anesthetic-induced amnesia. However, the molecular targets involved in this process are not fully characterized. GABAA receptors, especially the type with β3 subunits, represent a main molecular target of propofol. We therefore hypothesized that GABAA receptors with β3 subunits mediate the propofol-induced disturbance of cortico-hippocampal interactions. Methods: We used local field potential (LFP) recordings from chronically implanted cortical and hippocampal electrodes in wild-type and β3(N265M) knock-in mice. In the β3(N265M) mice, the action of propofol via β3subunit containing GABAA receptors is strongly attenuated. The analytical approach contained spectral power, phase locking, and mutual information analyses in the 2–16 Hz range to investigate propofol-induced effects on cortico-hippocampal interactions. Results: Propofol caused a significant increase in spectral power between 14 and 16 Hz in the cortex and hippocampus of wild-type mice. This increase was absent in the β3(N265M) mutant. Propofol strongly decreased phase locking of 6–12 Hz oscillations in wild-type mice. This decrease was attenuated in the β3(N265M) mutant. Finally, propofol reduced the mutual information between 6–16 Hz in wild-type mice, but only between 6 and 8 Hz in the β3(N265M) mutant. Conclusions: GABAA receptors containing β3 subunits contribute to frequency-specific perturbation of cortico-hippocampal interactions. This likely explains some of the amnestic actions of propofol. View Full-Text
Keywords: propofol; GABAA receptor; cortex; hippocampus; local field potential; mutual information; phase locking; synchrony propofol; GABAA receptor; cortex; hippocampus; local field potential; mutual information; phase locking; synchrony
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MDPI and ACS Style

Kreuzer, M.; Butovas, S.; García, P.S.; Schneider, G.; Schwarz, C.; Rudolph, U.; Antkowiak, B.; Drexler, B. Propofol Affects Cortico-Hippocampal Interactions via β3 Subunit-Containing GABAA Receptors. Int. J. Mol. Sci. 2020, 21, 5844.

AMA Style

Kreuzer M, Butovas S, García PS, Schneider G, Schwarz C, Rudolph U, Antkowiak B, Drexler B. Propofol Affects Cortico-Hippocampal Interactions via β3 Subunit-Containing GABAA Receptors. International Journal of Molecular Sciences. 2020; 21(16):5844.

Chicago/Turabian Style

Kreuzer, Matthias, Sergejus Butovas, Paul S García, Gerhard Schneider, Cornelius Schwarz, Uwe Rudolph, Bernd Antkowiak, and Berthold Drexler. 2020. "Propofol Affects Cortico-Hippocampal Interactions via β3 Subunit-Containing GABAA Receptors" International Journal of Molecular Sciences 21, no. 16: 5844.

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