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Activation of NMDA receptors blocks GABAergic inhibition in an in vitro model of epilepsy

Nature volume 326, pages 698–701 (1987)Cite this article

Abstract

The application of tetanic electrical stimuli to the stratum radiatum fibre pathway in the hippocampus in vitro produces an NMDA (N-methyl-D-aspartate) receptor-dependent enhancement of synaptic efficacy1–3. Repeated application of such stimuli produces a progressive enhancement of synaptic efficacy leading to the genesis of spontaneous and stimulation-evoked epileptiform discharges4,5. We have used this in vitro approach to explore the cellular mechanisms which underlie the kindling model of epilepsy. Kindling of the stratum radiatum fibre pathway in vitro induced a progressive, long-lasting reduction of both spontaneous and stimulation-evoked GABAergic (γ-amino butyric acid-mediated) inhibitory postsynaptic potentials (i.p.s.ps). The reduction of i.p.s.ps by kindling was associated with a profound decrease in the sensitivity of CA1 pyramidal neurons to ionophoretically applied GABA and an increase in sensitivity to NMDA. The reduction of i.p.s.ps and GABA sensitivity was prevented by kindling in the presence of the NMDA receptor antagonist D-2-amino-5-phosphonovalerate (D-APV). These results demonstrate that kindling-like stimulus patterns produce a reduction of GABAergic inhibition in the hippocampus resulting from a stimulus-induced postsynaptic activation of NMDA receptors. The modulation of GABAergic inhibition by NMDA receptors may cause the synaptic plasticity which underlies the kindling model of epilepsy.

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Author notes

  1. Armin Stelzer

    Present address: Department of Neurology, Room 4-408, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, New York, 10032, USA

  2. N. Traverse Slater

    Present address: Departments of Physiology and Psychiatry, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, Illinois, 60611, USA

  3. Armin Stelze: to whom correspondence should be addressed

Authors and Affiliations

  1. Physiology Institute, University of Munich, Pettenkoferstrasse 12, D-8000, Munich, 2, FRG

    Armin Stelzer, N. Traverse Slater & Gerrit ten Bruggencate

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  1. Armin Stelzer
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  2. N. Traverse Slater
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  3. Gerrit ten Bruggencate
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Stelzer, A., Slater, N. & ten Bruggencate, G. Activation of NMDA receptors blocks GABAergic inhibition in an in vitro model of epilepsy. Nature 326, 698–701 (1987). https://doi.org/10.1038/326698a0

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