Distinct types of ionic modulation of GABA actions in pyramidal cells and interneurons during electrical induction of hippocampal seizure-like network activity

Authors

  • Yoko Fujiwara-Tsukamoto,

    1. Department of System Neuroscience, Tokyo Metropolitan Institute for Neuroscience, 2–6 Musashidai, Fuchu, Tokyo 183–8526, Japan
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    • *

      Y.F.-T and Y.I. contributed equally to this work.

  • Yoshikazu Isomura,

    1. Department of System Neuroscience, Tokyo Metropolitan Institute for Neuroscience, 2–6 Musashidai, Fuchu, Tokyo 183–8526, Japan
    2. Neural Circuit Theory, RIKEN Brain Science Institute, Wako, Saitama 351–0198, Japan
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    • *

      Y.F.-T and Y.I. contributed equally to this work.

  • Michiko Imanishi,

    1. Department of System Neuroscience, Tokyo Metropolitan Institute for Neuroscience, 2–6 Musashidai, Fuchu, Tokyo 183–8526, Japan
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  • Tomoki Fukai,

    1. Neural Circuit Theory, RIKEN Brain Science Institute, Wako, Saitama 351–0198, Japan
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  • Masahiko Takada

    1. Department of System Neuroscience, Tokyo Metropolitan Institute for Neuroscience, 2–6 Musashidai, Fuchu, Tokyo 183–8526, Japan
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Dr Yoshikazu Isomura, as above.
E-mail: isomura@brain.riken.jp

Abstract

It has recently been shown that electrical stimulation in normal extracellular fluid induces seizure-like afterdischarge activity that is always preceded by GABA-dependent slow depolarization. These afterdischarge responses are synchronous among mature hippocampal neurons and driven by excitatory GABAergic input. However, the differences in the mechanisms whereby the GABAergic signals in pyramidal cells and interneurons are transiently converted from hyperpolarizing to depolarizing (and even excitatory) have remained unclear. To clarify the network mechanisms underlying this rapid GABA conversion that induces afterdischarges, we examined the temporal changes in GABAergic responses in pyramidal cells and/or interneurons of the rat hippocampal CA1 area in vitro. The extents of slow depolarization and GABA conversion were much larger in the pyramidal cell group than in any group of interneurons. Besides GABAA receptor activation, neuronal excitation by ionotropic glutamate receptors enhanced GABA conversion in the pyramidal cells and consequent induction of afterdischarge. The slow depolarization was confirmed to consist of two distinct phases; an early phase that depended primarily on GABAA-mediated postsynaptic Cl accumulation, and a late phase that depended on extracellular K+ accumulation, both of which were enhanced by glutamatergic neuron excitation. Moreover, extracellular K+ accumulation augmented each oscillatory response of the afterdischarge, probably by further Cl accumulation through K+-coupled Cl transporters. Our findings suggest that the GABA reversal potential may be elevated above their spike threshold predominantly in the pyramidal cells by biphasic Cl intrusion during the slow depolarization in GABA- and glutamate-dependent fashion, leading to the initiation of seizure-like epileptiform activity.

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