title: PSD-95 regulates synaptic kainate receptors at mouse hippocampal mossy fiber-CA3 synapses.
abstract: Kainate-type glutamate receptors (KARs) are the third class of ionotropic glutamate receptors whose activation leads to the unique roles in regulating synaptic transmission and circuit functions. In contrast to AMPA receptors (AMPARs), little is known about the mechanism of synaptic localization of KARs. PSD-95, a major scaffold protein of the postsynaptic density, is a candidate molecule that regulates the synaptic KARs. Although PSD-95 was shown to bind directly to KARs subunits, it has not been tested whether PSD-95 regulates synaptic KARs in intact synapses. Using PSD-95 knockout mice, we directly investigated the role of PSD-95 in the KARs-mediated components of synaptic transmission at hippocampal mossy fiber-CA3 synapse, one of the synapses with the highest density of KARs. Mossy fiber EPSCs consist of AMPA receptor (AMPAR)-mediated fast component and KAR-mediated slower component, and the ratio was significantly reduced in PSD-95 knockout mice. The size of KARs-mediated field EPSP reduced in comparison with the size of the fiber volley. Analysis of KARs-mediated miniature EPSCs also suggested reduced synaptic KARs. All the evidence supports critical roles of PSD-95 in regulating synaptic KARs.
authors.affiliation: Department of Neurobiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan; Japan Society for the Promotion of Science, Tokyo 102-0083, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Suzuki
authors.affiliation: Department of Neurobiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. Electronic address: kamiya@med.hokudai.ac.jp.
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Kamiya
mesh_terms: D000818:Animals; D000076122:Disks Large Homolog 4 Protein; D019706:Excitatory Postsynaptic Potentials; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism*; D018091:Receptors, AMPA / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D008565:Membrane Proteins; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; C501447:Dlg4 protein, mouse
keywords: Hippocampus; Kainate receptor; PSD-95; Postsynaptic density