Altered synaptic physiology and reduced susceptibility to kainate- induced secures in GluR6-deficient mice

Christophe Mulle, Andreas Sailer, Isabel Pérez-Otaño, Heather Dickinson-Anson, Pablo E. Castillo, Ingrid Bureau, Cornelia Maron, Fred H. Gage, Jeffrey R. Mann, Bernhard Bettler, Stephen F. Heinemann

Research output: Contribution to journalArticle

355 Citations (Scopus)

Abstract

L-glutamate, the neurotransmitter of the majority of excitatory synapses in the brain, acts on three classes of ionotropic receptors: NMDA (N-methyl- D-aspartate), AMPA (α-amino-3-hydroxy-5methyl-4-isoxazole propionic acid) and kainate receptors. Little is known about the physiological role of kainate receptors because in many experimental situations it is not possible to distinguish them from AMPA receptors. Mice with disrupted kainate receptor genes enable the study of the specific role of kainate receptors in synaptic transmission as well as in the neurotoxic effects of kainate. We have now generated mutant mice lacking the kainatereceptor subunit GIuR6. The hippocampal neurons in the CA3 region of these mutant mice are much less sensitive to kainate. In addition, a postsynaptic kainate current evoked in CA3 neurons by a train of stimulation of the mossy fibre system is absent in the mutant. We find that GluR6-deficient mice are less susceptible to systemic administration of kainate, as judged by onset of seizures and by the activation of immediate early genes in the hippocampus. Our results indicate that kainate receptors containing the GIuR6 subunit are important in synaptic transmission as well as in the epileptogenic effects of kainate.

Original languageEnglish (US)
Pages (from-to)601-605
Number of pages5
JournalNature
Volume392
Issue number6676
DOIs
StatePublished - Apr 9 1998
Externally publishedYes

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Kainic Acid Receptors
Kainic Acid
Synaptic Transmission
Isoxazoles
Neurons
Synaptic Potentials
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Immediate-Early Genes
AMPA Receptors
N-Methyl-D-Aspartate Receptors
Synapses
Neurotransmitter Agents
Glutamic Acid
Hippocampus
Seizures
Brain
Genes

ASJC Scopus subject areas

  • General

Cite this

Mulle, C., Sailer, A., Pérez-Otaño, I., Dickinson-Anson, H., Castillo, P. E., Bureau, I., ... Heinemann, S. F. (1998). Altered synaptic physiology and reduced susceptibility to kainate- induced secures in GluR6-deficient mice. Nature, 392(6676), 601-605. https://doi.org/10.1038/33408

Altered synaptic physiology and reduced susceptibility to kainate- induced secures in GluR6-deficient mice. / Mulle, Christophe; Sailer, Andreas; Pérez-Otaño, Isabel; Dickinson-Anson, Heather; Castillo, Pablo E.; Bureau, Ingrid; Maron, Cornelia; Gage, Fred H.; Mann, Jeffrey R.; Bettler, Bernhard; Heinemann, Stephen F.

In: Nature, Vol. 392, No. 6676, 09.04.1998, p. 601-605.

Research output: Contribution to journalArticle

Mulle, C, Sailer, A, Pérez-Otaño, I, Dickinson-Anson, H, Castillo, PE, Bureau, I, Maron, C, Gage, FH, Mann, JR, Bettler, B & Heinemann, SF 1998, 'Altered synaptic physiology and reduced susceptibility to kainate- induced secures in GluR6-deficient mice', Nature, vol. 392, no. 6676, pp. 601-605. https://doi.org/10.1038/33408
Mulle C, Sailer A, Pérez-Otaño I, Dickinson-Anson H, Castillo PE, Bureau I et al. Altered synaptic physiology and reduced susceptibility to kainate- induced secures in GluR6-deficient mice. Nature. 1998 Apr 9;392(6676):601-605. https://doi.org/10.1038/33408
Mulle, Christophe ; Sailer, Andreas ; Pérez-Otaño, Isabel ; Dickinson-Anson, Heather ; Castillo, Pablo E. ; Bureau, Ingrid ; Maron, Cornelia ; Gage, Fred H. ; Mann, Jeffrey R. ; Bettler, Bernhard ; Heinemann, Stephen F. / Altered synaptic physiology and reduced susceptibility to kainate- induced secures in GluR6-deficient mice. In: Nature. 1998 ; Vol. 392, No. 6676. pp. 601-605.
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