title: Characterization of physiological phenotypes of dentate gyrus synapses of PDZ1/2 domain-deficient PSD-95-knockin mice.
abstract: The hippocampal formation is involved in several important brain functions of animals, such as memory formation and pattern separation, and the synapses in the dentate gyrus (DG) play critical roles as the first step in the hippocampal circuit. Previous studies have reported that mice with genetic modifications of the PDZ1/2 domains of postsynaptic density (PSD)-95 exhibit altered synaptic properties in the DG and impaired hippocampus-dependent behaviors. Based on the involvement of the DG in the regulation of behaviors, these data suggest that the abnormal behavior of these knockin (KI) mice is due partly to altered DG function. Precise understanding of the phenotypes of these mutant mice requires characterization of the synaptic properties of the DG, and here we provide detailed studies of DG synapses. We have demonstrated global changes in the PSD membrane-associated guanylate kinase expression pattern in the DG of mutant mice, and DG synapses in these mice exhibited increased long-term potentiation under a wide range of stimulus intensities, although the N-methyl-d-aspartic acid receptor dependence of the long-term potentiation was unchanged. Furthermore, our data also indicate increased silent synapses in the DG of the KI mice. These findings suggest that abnormal protein expression and physiological properties disrupt the function of DG neurons in these KI mice.
authors.affiliation: Cellular and Structural Physiology Institute, Nagoya University, Nagoya, 464-8601, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nagura
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Doi
authors.affiliation: Cellular and Structural Physiology Institute, Nagoya University, Nagoya, 464-8601, Japan.|Department of Basic Medical Science, Graduate School of Pharmaceutical Science, Nagoya University, Nagoya, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fujiyoshi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D000076122:Disks Large Homolog 4 Protein; D019706:Excitatory Postsynaptic Potentials; D051528:Guanylate Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017774:Long-Term Potentiation; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010641:Phenotype; D000072417:Protein Domains; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000502:physiology
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D051528:Guanylate Kinases
keywords: PSD-95; dentate gyrus; hippocampus; silent synapse; synaptic plasticity