Comprehensive behavioural study of GluR4 knockout mice: implication in cognitive function

Authors

  • N. Sagata,

    1. Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka
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  • A. Iwaki,

    1. Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka
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  • T. Aramaki,

    1. Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka
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  • K. Takao,

    1. Laboratory for Genetic Engineering and Functional Genomics, Frontier Technology Center, Kyoto University Faculty of Medicine, Kyoto
    2. Japan Science and Technology Agency (JST), Institute for Bioinformatics Research and Development (BIRD), Core Research for Evolutional Science and Technology (CREST), Kawaguchi
    3. Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake
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  • S. Kura,

    1. Department of Medical Biophysics & Radiation Biology
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  • T. Tsuzuki,

    1. Department of Medical Biophysics & Radiation Biology
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  • R. Kawakami,

    1. Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan
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  • I. Ito,

    1. Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan
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  • T. Kitamura,

    1. Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan
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  • H. Sugiyama,

    1. Department of Biology, Faculty of Science, Kyushu University, Fukuoka, Japan
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  • T. Miyakawa,

    1. Laboratory for Genetic Engineering and Functional Genomics, Frontier Technology Center, Kyoto University Faculty of Medicine, Kyoto
    2. Japan Science and Technology Agency (JST), Institute for Bioinformatics Research and Development (BIRD), Core Research for Evolutional Science and Technology (CREST), Kawaguchi
    3. Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake
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  • Y. Fukumaki

    Corresponding author
    1. Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka
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Y. Fukumaki, Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail:yfukumak@gen.kyushu-u.ac.jp

Abstract

Fast excitatory transmission in the mammalian central nervous system is mediated by AMPA-type glutamate receptors. The tetrameric AMPA receptor complexes are composed of four subunits, GluR1–4. The GluR4 subunit is highly expressed in the cerebellum and the early postnatal hippocampus and is thought to be involved in synaptic plasticity and the development of functional neural circuitry through the recruitment of other AMPA receptor subunits. Previously, we reported an association of the human GluR4 gene (GRIA4) with schizophrenia. To examine the role of the GluR4 subunit in the higher brain function, we generated GluR4 knockout mice and conducted electrophysiological and behavioural analyses. The mutant mice showed normal long-term potentiation (LTP) in the CA1 region of the hippocampus. The GluR4 knockout mice showed mildly improved spatial working memory in the T-maze test. Although the retention of spatial reference memory was intact in the mutant mice, the acquisition of spatial reference memory was impaired in the Barnes circular maze test. The GluR4 knockout mice showed impaired prepulse inhibition. These results suggest the involvement of the GluR4 subunit in cognitive function.

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