Department of Anesthesiology

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γ-Aminobutyric Acid Type A Receptor Potentiation Inhibits Learning in a Computational Network Model.

Titleγ-Aminobutyric Acid Type A Receptor Potentiation Inhibits Learning in a Computational Network Model.
Publication TypeJournal Article
Year of Publication2018
AuthorsStorer KP, Reeke GN
JournalAnesthesiology
Date Published2018 Apr 17
ISSN1528-1175
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.

DOI10.1097/ALN.0000000000002230
Alternate JournalAnesthesiology
PubMed ID29664887