Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
Sustained increase in α5GABAA receptor function impairs memory after anesthesia
Agnieszka A. Zurek, … , Eric W.R. Salter, Beverley A. Orser
Agnieszka A. Zurek, … , Eric W.R. Salter, Beverley A. Orser
Published November 3, 2014
Citation Information: J Clin Invest. 2014;124(12):5437-5441. https://doi.org/10.1172/JCI76669.
View: Text | PDF
Brief Report Neuroscience

Sustained increase in α5GABAA receptor function impairs memory after anesthesia

  • Text
  • PDF
Abstract

Many patients who undergo general anesthesia and surgery experience cognitive dysfunction, particularly memory deficits that can persist for days to months. The mechanisms underlying this postoperative cognitive dysfunction in the adult brain remain poorly understood. Depression of brain function during anesthesia is attributed primarily to increased activity of γ-aminobutyric acid type A receptors (GABAARs), and it is assumed that once the anesthetic drug is eliminated, the activity of GABAARs rapidly returns to baseline and these receptors no longer impair memory. Here, using a murine model, we found that a single in vivo treatment with the injectable anesthetic etomidate increased a tonic inhibitory current generated by α5 subunit–containing GABAARs (α5GABAARs) and cell-surface expression of α5GABAARs for at least 1 week. The sustained increase in α5GABAAR activity impaired memory performance and synaptic plasticity in the hippocampus. Inhibition of α5GABAARs completely reversed the memory deficits after anesthesia. Similarly, the inhaled anesthetic isoflurane triggered a persistent increase in tonic current and cell-surface expression of α5GABAARs. Thus, α5GABAAR function does not return to baseline after the anesthetic is eliminated, suggesting a mechanism to account for persistent memory deficits after general anesthesia.

Authors

Agnieszka A. Zurek, Jieying Yu, Dian-Shi Wang, Sean C. Haffey, Erica M. Bridgwater, Antonello Penna, Irene Lecker, Gang Lei, Tom Chang, Eric W.R. Salter, Beverley A. Orser

×

Figure 1

Etomidate impairs memory and synaptic plasticity but does not modify the function of postsynaptic GABAARs.

Options: View larger image (or click on image) Download as PowerPoint
Etomidate impairs memory and synaptic plasticity but does not modify the...
(A) Memory performance on the novel object recognition task after etomidate (8 mg/kg, i.p.) or dexmedetomidine (200 μg/kg, i.p.) and (B) total interaction time with both objects during testing (n = 9–12, 1-way ANOVA at each time point, Dunnett’s post-test). (C) Plasticity at Schaffer collateral-CA1 synapses 24 hours after treatment. Insets, representative traces recorded before (a) and 60 minutes after (b) 20-Hz stimulation. Bar graph summarizes data for the last 5 minutes of recording 24 hours (n = 7) or 1 week (n = 9–10) after etomidate (unpaired, 2-tailed Student’s t test at each time point). (D) Recordings of mIPSCs in CA1 pyramidal neurons 24 hours after etomidate. Left lower panel shows the averaged traces from control (red) and etomidate-treated (black) mice. Middle and right lower panels show the cumulative amplitude (P = 0.89) and the cumulative frequency (P = 0.25) distributions (Kolmogorov-Smirnov test, 125 events). Ctrl, vehicle control; Etom, etomidate; Dex, dexmedetomidine. Data are shown as mean ± SEM. ***P < 0.001.
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts