title: Identification of the kainate receptor subunits underlying modulation of excitatory synaptic transmission in the CA3 region of the hippocampus.
abstract: To understand the physiological role of kainate receptors and their participation in seizure induction in animal models of epilepsy, it will be necessary to develop a comprehensive description of their action in the CA3 region of the hippocampus. Activation of presynaptic kainate receptors depresses excitatory synaptic transmission at mossy fiber and associational-commissural inputs to CA3 pyramidal neurons (Vignes et al., 1998; Bortolotto et al., 1999; Kamiya and Ozawa, 2000). In this study, we use gene-targeted mice lacking glutamate receptor 5 (GluR5) or GluR6 kainate receptor subunits to identify the receptor subunits that comprise the kainate receptors responsible for presynaptic modulation of CA3 transmission. We found that bath application of kainate (3 microm) profoundly reduced EPSCs at mossy fiber and collateral synapses in neurons from wild-type and GluR5(-/-) mice but had no effect on EPSCs in neurons from GluR6(-/-) mice. These results therefore contrast with previous studies that supported a role for GluR5-containing receptors at mossy fiber and associational-commissural synapses (Vignes et al., 1998; Bortolotto et al., 1999). Surprisingly, at perforant path synapses kainate receptor activation enhanced transmission; this potentiation was abolished in both GluR5 and GluR6 knock-out mice. Kainate receptors thus play multiple and complex roles to modulate excitatory synaptic transmission in the CA3 region of the hippocampus.
authors.affiliation: Molecular Neurobiology Laboratory and Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. contractor@salk.edu
authors.forename: A
authors.initials: A
authors.lastname: Contractor
authors.forename: G T
authors.initials: GT
authors.lastname: Swanson
authors.forename: A
authors.initials: A
authors.lastname: Sailer
authors.forename: S
authors.initials: S
authors.lastname: O'Gorman
authors.forename: S F
authors.initials: SF
authors.lastname: Heinemann
mesh_terms: D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D019580:Perforant Pathway / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000172:deficiency / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017661:Receptors, Presynaptic / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D000097806:GluK2 Kainate Receptor
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D007608:Kainic Acid; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017661:Receptors, Presynaptic; D000097806:GluK2 Kainate Receptor