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Glutamatergic Modulation of GABAergic Signaling Among Hippocampal Interneurons: Novel Mechanisms Regulating Hippocampal Excitability
Author(s) -
Kullmann Dimitri M.,
Semyanov Alexey
Publication year - 2002
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.43.s.5.12.x
Subject(s) - kainate receptor , neuroscience , gabaergic , metabotropic glutamate receptor , glutamatergic , interneuron , glutamate receptor , metabotropic receptor , biology , hippocampal formation , excitatory postsynaptic potential , long term depression , chemistry , receptor , inhibitory postsynaptic potential , ampa receptor , biochemistry
Summary: Purpose: Because interneurons play a central role in regulating the excitability of the hippocampal formation, it is important to understand the mechanisms that modulate γ‐aminobutyric acid (GABA)ergic signaling among them. This study addresses the modulation of GABA release from interneuron terminals by presynaptic glutamate receptors. Methods: Whole‐cell recordings were obtained from CA1 stratum radiatum interneurons in guinea pig hippocampal slices. Selective agonists and blockers of glutamate receptors were used to study modulation of GABAergic transmission by group III metabotropic receptors or kainate receptors. Antidromic action‐potential initiation also was analyzed by stimulating the axons of interneurons. Results: Agonists of group III metabotropic glutamate receptors attenuated monosynaptic GABAergic signals in interneurons, but not in pyramidal neurons, in agreement with anatomic evidence on the distribution of these receptors. Submicromolar kainate enhanced the frequency and amplitude of spontaneous GABAergic signals in interneurons. Kainate also depolarized the axons of hippocampal interneurons, and triggered spontaneous ectopic action potentials in axons. Synaptically released glutamate reproduced many of the effects of both agonists, implying that these receptors can sense the ambient glutamate concentration, and therefore indirectly respond to the excitatory traffic in the hippocampus. When the two classes of receptors were stimulated simultaneously, complex interactions were obtained. Conclusions: Group III metabotropic receptors and kainate receptors profoundly affect GABAergic signaling among interneurons of the hippocampus. Glutamatergic modulation of GABAergic signaling among interneurons represents a novel class of mechanisms that potentially plays a major role in determining the initiation, propagation, and termination of seizures.