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Kindling enhances kainate receptor‐mediated depression of GABAergic inhibition in rat granule cells
Author(s) -
Behr Joachim,
Gebhardt Christine,
Heinemann Uwe,
Mody Istvan
Publication year - 2002
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2002.02152.x
Subject(s) - kainate receptor , dentate gyrus , inhibitory postsynaptic potential , neuroscience , glutamate receptor , ampa receptor , postsynaptic potential , chemistry , gabaergic , gabaa receptor , hippocampal formation , long term depression , biology , receptor , pharmacology , biochemistry
Several lines of evidence indicate a substantial contribution of kainate receptors to temporal lobe seizures. The activation of kainate receptors located on hippocampal inhibitory interneurons was shown to reduce GABA release. A reduced GABA release secondary to kainate receptor activation could contribute to an enhanced seizure susceptibility. As the dentate gyrus serves a pivotal gating function in the spread of limbic seizures, we tested the role of kainate receptors in the regulation of GABA release in the dentate gyrus of control and kindled animals. Application of glutamate (100 µ m ) in the presence of the NMDA receptor antagonist d ‐APV and the AMPA receptor antagonist, SYM 2206 caused a slight depression of evoked monosynaptic inhibitory postsynaptic currents (IPSCs) in control, but a substantial decrease in kindled dentate granule cells. The observation that kainate receptor activation altered paired‐pulse depression and reduced the frequency of TTX‐insensitive miniature IPSCs without affecting their amplitude is consistent with a presynaptic action on the inhibitory terminal to reduce GABA release. In kindled preparations, neither glutamate (100 µ m ) nor kainate (10 µ m ) applied in a concentration known to depolarize hippocampal interneurons led to an increase of the TTX‐sensitive spontaneous IPSC frequency nor to changes of the postsynaptic membrane properties. Consistently, the inhibitory effect on evoked IPSCs was not affected by the presence of the GABA B receptor antagonist, CGP55845A, thus excluding a depression by an enhanced release of GABA acting on presynaptic GABA B receptors. The enhanced inhibition of GABA release following presynaptic kainate receptor activation favours a use‐dependent hyperexcitability in the epileptic dentate gyrus.