Altered synaptic physiology and reduced susceptibility to kainate-induced seizures in GluR6-deficient mice.
Nature. 1998-04-01; 392(6676): 601-605
Read on PubMed
1. Nature. 1998 Apr 9;392(6676):601-5.
Altered synaptic physiology and reduced susceptibility to kainate-induced
seizures in GluR6-deficient mice.
Mulle C(1), Sailer A, Pérez-Otaño I, Dickinson-Anson H, Castillo PE, Bureau I,
Maron C, Gage FH, Mann JR, Bettler B, Heinemann SF.
(1)Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies,
La Jolla, California 92037, USA.
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 (alpha-amino-3-hydroxy-5-methyl-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 kainate-receptor subunit GluR6. 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 GluR6 subunit are important in synaptic transmission as
well as in the epileptogenic effects of kainate.
PMID: 9580260 [Indexed for MEDLINE]