Journal ArticleDOI
Altered synaptic physiology and reduced susceptibility to kainate-induced seizures in GluR6-deficient mice
Christophe Mulle,Andreas W. 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 +10 more
TLDR
It is found 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.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 (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.read more
Citations
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Journal ArticleDOI
Glutamate receptor function in learning and memory
TL;DR: The role played by the three main glutamate receptor classes in learning and memory is identified more specifically and problems of interpretation are outlined and a specific involvement of AMPARs in the regulation of neuronal excitation related to learning is proposed.
Journal ArticleDOI
Kindling and status epilepticus models of epilepsy: rewiring the brain.
TL;DR: This review focuses on the remodeling of brain circuitry associated with epilepsy, particularly in excitatory glutamate and inhibitory GABA systems, including alterations in synaptic efficacy, growth of new connections, and loss of existing connections.
Journal ArticleDOI
(Patho)physiological Significance of the Serum- and Glucocorticoid-Inducible Kinase Isoforms
Florian Lang,Christoph Böhmer,Monica Palmada,Guiscard Seebohm,Nathalie Strutz-Seebohm,Volker Vallon +5 more
TL;DR: The serum- and glucocorticoid-inducible kinase-1 (SGK1) is ubiquitously expressed and under genomic control by cell stress and hormones, and may play an active role in a multitude of pathophysiological conditions.
Journal ArticleDOI
Kainate, a double agent that generates seizures: two decades of progress.
Yehezkel Ben-Ari,Rosa Cossart +1 more
TL;DR: This work focuses on target and subunit-specific effects of kainate on hippocampal pyramidal neurons and interneurons that lead to an excitation of both types of neurons and thus to the parallel increase of glutamatergic and GABAergic spontaneous currents.
Journal ArticleDOI
Neuronal Cell Death
TL;DR: In a short review such as this, it is not possible to establish precedence for all ideas or mechanisms, many of which originate from (or are still confined to) studies outside the nervous system, so wherever possible, the interested reader is illustrated by citing recent articles involving neurons.
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