Kainate receptors presynaptically downregulate GABAergic inhibition in the rat hippocampus.
Using microcultured neurons and hippocampal slices, we found that under conditions that completely block AMPA receptors, kainate induces a reduction in the effectiveness of GABAergic synaptic inhibition. Evoked inhibitory postsynaptic currents (IPSCs) were decreased by kainate by up to 90%, showing a bell-shaped dose-response curve similar to that of native kainate-selective receptors. The down-regulation of GABAergic inhibition was not affected by antagonism of metabotropic receptors, while it was attenuated by CNQX. Kainate increased synaptic failures and reduced the frequency of miniature IPSCs, indicating a presynaptic locus of action. In vivo experiments using brain dialysis demonstrated that kainate reversibly abolished recurrent inhibition and induced an epileptic-like electroencephalogram (EEG) activity. These results indicate that kainate receptor activation down-regulates GABAergic inhibition by modulating the reliability of GABA synapses.
Rodríguez-Moreno
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A
Department of Neural Plasticity, Instituto Cajal, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Herreras
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Lerma
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J
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002478:Cells, Cultured; D004558:Electric Stimulation; D004569:Electroencephalography / Q000187:drug effects; D004622:Embryo, Mammalian; D004827:Epilepsy; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D007839:Functional Laterality; D018756:GABA Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology*; D009474:Neurons / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001640:Bicuculline; D018756:GABA Antagonists; D007608:Kainic Acid; D018092:Kainic Acid Receptors; D017661:Receptors, Presynaptic; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid