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

Matthias Kreuzer, Sergejus Butovas, Paul S. García, Gerhard Schneider, Cornelius Schwarz, Uwe Rudolph, Bernd Antkowiak, Berthold Drexler

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number5844
Pages (from-to)1-15
Number of pages15
JournalInternational journal of molecular sciences
Volume21
Issue number16
DOIs
StatePublished - Aug 14 2020

Keywords

  • Cortex
  • GABAA receptor
  • Hippocampus
  • Local field potential
  • Mutual information
  • Phase locking
  • Propofol
  • Synchrony

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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