Newly Published
Perioperative Medicine  |   April 2018
γ-Aminobutyric Acid Type A Receptor Potentiation Inhibits Learning in a Computational Network Model
Author Notes
  • From the Department of Anesthesiology, Weill Cornell Medical College, New York, New York (K.P.S)
  • the Laboratory of Biological Modeling, The Rockefeller University, New York, New York (K.P.S, G.N.R.)
  • the Department of Surgery, Flinders University, Adelaide, Australia (K.P.S).
  • Submitted for publication September 8, 2017. Accepted for publication March 15, 2018.
    Submitted for publication September 8, 2017. Accepted for publication March 15, 2018.×
  • The work presented in this article has been presented at the Anesthesiology 2016 Annual Meeting in Chicago, Illinois, October 23, 2016.
    The work presented in this article has been presented at the Anesthesiology 2016 Annual Meeting in Chicago, Illinois, October 23, 2016.×
  • Acknowledgments: The authors thank Robert Veselis, M.D., Department of Anesthesiology, Memorial Sloan Kettering Cancer Center, Montvale, New Jersey, for insightful comments on the manuscript.
    Acknowledgments: The authors thank Robert Veselis, M.D., Department of Anesthesiology, Memorial Sloan Kettering Cancer Center, Montvale, New Jersey, for insightful comments on the manuscript.×
  • Research Support: Supported by a Foundation for Anesthesia Education and Research (Shaumburg, Illinois) Mentored Research Training Grant (to Dr. Storer).
    Research Support: Supported by a Foundation for Anesthesia Education and Research (Shaumburg, Illinois) Mentored Research Training Grant (to Dr. Storer).×
  • Competing Interests: The authors declare no competing interests.
    Competing Interests: The authors declare no competing interests.×
  • Correspondence: Address correspondence to Dr. Storer: Department of Anesthesiology, Weill Cornell Medical College, 1300 York Ave., New York, New York 10021. kis9029@med.cornell.edu. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Central and Peripheral Nervous Systems / Pharmacology
Perioperative Medicine   |   April 2018
γ-Aminobutyric Acid Type A Receptor Potentiation Inhibits Learning in a Computational Network Model
Anesthesiology Newly Published on April 16, 2018. doi:10.1097/ALN.0000000000002230
Anesthesiology Newly Published on April 16, 2018. doi:10.1097/ALN.0000000000002230
Abstract

Background: Propofol produces memory impairment at concentrations well below those abolishing consciousness. Episodic memory, mediated by the hippocampus, is most sensitive. Two potentially overlapping scenarios may explain how γ-aminobutyric acid receptor type A (GABAA) potentiation by propofol disrupts episodic memory—the first mediated by shifting the balance from excitation to inhibition while the second involves disruption of rhythmic oscillations. We use a hippocampal network model to explore these scenarios. The basis for these experiments is the proposal that the brain represents memories as groups of anatomically dispersed strongly connected neurons.

Methods: A neuronal network with connections modified by synaptic plasticity was exposed to patterned stimuli, after which spiking output demonstrated evidence of stimulus-related neuronal group development analogous to memory formation. The effect of GABAA potentiation on this memory model was studied in 100 unique networks.

Results: GABAA potentiation consistent with moderate propofol effects reduced neuronal group size formed in response to a patterned stimulus by around 70%. Concurrently, accuracy of a Bayesian classifier in identifying learned patterns in the network output was reduced. Greater potentiation led to near total failure of group formation. Theta rhythm variations had no effect on group size or classifier accuracy.

Conclusions: Memory formation is widely thought to depend on changes in neuronal connection strengths during learning that enable neuronal groups to respond with greater facility to familiar stimuli. This experiment suggests the ability to form such groups is sensitive to alteration in the balance between excitation and inhibition such as that resulting from administration of a γ-aminobutyric acid–mediated anesthetic agent.