Molecular Analysis of Brain System Controls under the Pure Genetic Background

2009 Fiscal Year Final Research Report

• Project/Area Number: 17024011
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: MISHINA Masayoshi The University of Tokyo, 大学院・医学系研究科, 教授 (80144351)
• Co-Investigator(Kenkyū-buntansha): UEMURA Takeshi 東京大学, 大学院・医学系研究科, 助教 (00372368) ; TAKEUCHI Tomonori 東京大学, 大学院・医学系研究科, 助教 (50323613)
• Project Period (FY): 2005 – 2009
• Keywords: 記憶 / 学習 / 情動 / 海馬 / 線条体 / 小脳 / 標的遺伝子組換え / 誘導型Cre組換え酵素

Research Abstract

We established C57BL/6 mouse lines expressing Cre or inducible CrePR recombinase genes under the control of hippocampus-, striatum- or cerebellum-specific promoters. By the use of the brain-region selective gene manipulation system, we have analyzed brain systems that control learning and memory. We found that the striatum is essential for the formation of fear memory under weak unconditioned stimulus. Furthermore, we showed that the facilitation of LTD induction at parallel fiber-Purkinje cell synapses enhances the optokinetic response adaptation, indicating that the synaptic plasticity at the specific site of a motor control circuit determines the efficacy of a motor learning.

Research Products

• [Journal Article] Trans-synaptic interaction of GluRδ2 and neurexin through Cbln1 mediates synapse formation in the cerebellum (2010)
  • Author(s): Uemura, T., Lee, S., Yasumura, M., Takeuchi, T., Yoshida, T., Ra, M., Taguchi, R., Sakimura, K., Mishina, M.
  • Journal Title: Cell (in press)
  • Peer Reviewed
• [Journal Article] Strain differences in stress responsivity are associated with divergent amygdala gene expression and glutamate-mediated neuronal excitability (2010)
  • Author(s): Mozhui, K., Karlsson, R-M., Kash, T., Ihne, J., Norcross, M., Patel, S., Farrell, M., Hill, E., Martin, K., Camp, M., Fitzgerald, P., Ciobanu, D., Sprengel, R., Mishina, M., Wellman, C., Winder, D., Williams, R.W., Holmes, A.
  • Journal Title: J. Neurosci. 30 Pages: 5357-5367
  • Peer Reviewed
• [Journal Article] Estrogen regulates the expression of N-methyl-D-aspartate (NMDA) receptor subunit epsilon 4 (Grin2d), that is essential for the normal sexual behavior in female mice (2010)
  • Author(s): Ikeda, K., Fukushima, T., Ogura, H., Tsukui, T., Mishina, M., Muramatsu, M., Inoue, S.
  • Journal Title: FEBS Lett 584 Pages: 806-810
  • Peer Reviewed
• [Journal Article] Influence of parallel fiber-Purkinje cell synapse formation on postnatal development of climbing fiber-Purkinje cell synapses: Lessons from GluRδ2 knockout mice (2009)
  • Author(s): Hashimoto, K., Yoshida, T., Sakimura, K., Mishina, M., Watanabe, M., Kano, M.
  • Journal Title: Neuroscience 162 Pages: 601-611
  • Peer Reviewed
• [Journal Article] NR2A at CA1 synapses is obligatory for the susceptibility of hippocampal plasticity to sleep loss (2009)
  • Author(s): Longordo, F., Kopp, C., Mishina, M., Lujan, R., Luthi, A.
  • Journal Title: J. Neurosci. 29 Pages: 9026-9041
  • Peer Reviewed
• [Journal Article] Ablation of NMDA receptors enhances the excitability of hippocampal CA3 neurons (2009)
  • Author(s): Fukushima, F., Nakao, K., Shinoe, T., Fukaya, M., Muramatsu, S., Sakimura, K., Kataoka, H., Mori, H., Watanabe, M., Manabe, T., Mishina, M.
  • Journal Title: PLoS ONE 4 Pages: e3993
  • Peer Reviewed
• [Journal Article] A novel form of memory for auditory fear conditioning at a low-intensity unconditioned stimulus (2009)
  • Author(s): Kishioka, A., Fukushima, F., Ito, T., Kataoka, H., Mori, H., Ikeda, T., Itohara, S., Sakimura, K., Mishina, M.
  • Journal Title: PLoS ONE 4 Pages: e4157
  • Peer Reviewed
• [Journal Article] The amino-terminal domain of glutamate receptorδ2 triggers presynaptic differentiation (2008)
  • Author(s): Uemura, T., Mishina, M.
  • Journal Title: Biochem. Biophys. Res. Commun. 377 Pages: 1315-1319
  • Peer Reviewed
• [Journal Article] Role of major NMDAR or AMPA receptor subunits in MK-801 potentiation of ethanol intoxication (2008)
  • Author(s): Palachick, B., Chen, Y. -C., Enoch, A.J., Karlsson, R. -M., Mishina, M., Holmes, A.
  • Journal Title: Alcohol. Clin. Exp. Res. 32 Pages: 1479-1492
  • Peer Reviewed
• [Journal Article] Enhancement of both long-term depression induction and optokinetic response adaptation in mice lacking Delphilin (2008)
  • Author(s): Takeuchi, T., Ohtsuki, G., Yoshida, T., Fukaya, M., Wainai, T., Yamashita, M., Yamazaki, Y., Mori, H., Sakimura, K., Kawamoto, S., Watanabe, M., Hirano, T., Mishina, M.
  • Journal Title: PLoS ONE 3 Pages: e2297
  • Peer Reviewed
• [Journal Article] Role of the internal Shank-binding segment of glutamate receptorδ2 in synaptic localization and cerebellar functions (2008)
  • Author(s): Yasumura, M., Uemura, T., Yamasaki, M., Sakimura, K., Watanabe, M., Mishina, M.
  • Journal Title: Neurosci. Lett. 433 Pages: 146-151
  • Peer Reviewed
• [Journal Article] Effects of FAK ablation on cerebellar foliation, Bergmann glia positioning and climbing fiber territory on Purkinje cells (2008)
  • Author(s): Watanabe, F., Miyazaki, T., Takeuchi, T., Fukaya, M., Nomura, T., Noguchi, S., Mori, H., Sakimura, K., Watanabe, M., Mishina, M.
  • Journal Title: Eur. J. Neurosci. 27 Pages: 836-854
  • Peer Reviewed
• [Journal Article] Differential regulation of synaptic plasticity and cerebellar motor learning by the C-terminal PDZ-binding motif of GluRδ2. (2008)
  • Author(s): Kakegawa, W., Miyzaki, T., Emi, K., Matsuda, K., Kohda, K., Motohashi, J., Mishina, M., Kawahara, S., Watanabe, M., Yuzaki, M.
  • Journal Title: J. Neurosci. 28 Pages: 1460-1468
  • Peer Reviewed
• [Journal Article] Impaired discrimination learning in mice lacking the NMDA receptor NR2A subunit. (2008)
  • Author(s): Brigman, J.L., Feyder, M., Saksida, L.M., Bussey, T.J., Mishina, M., Holmes, A.
  • Journal Title: Learn. Mem. 15 Pages: 50-54
  • Peer Reviewed
• [Journal Article] Regulation of long-term depression and climbing fiber territory by glutamate receptorδ2 at parallel fiber synapses through its C-terminal domain in cerebellar Purkinje cells (2007)
  • Author(s): Uemura, T., Kakizawa, S., Yamasaki, M., Sakimura, K., Watanabe, M., Iino, M., Mishina, M.
  • Journal Title: J. Neurosci. 27 Pages: 12096-12108
  • Peer Reviewed
• [Journal Article] Activation of NMDA receptors promotes dendritic spine development through MMP-mediated ICAM-5 cleavage (2007)
  • Author(s): Tian, L., Stefanidakis, M., Ning, L., Lint, P.V., Nyman-Huttunen, H., Libert, C., Itohara, S., Mishina, M., Rauvala, H., Gahmberg, C.G.
  • Journal Title: J. Cell Biol. 178 Pages: 687-700
  • Peer Reviewed
• [Journal Article] Nitric oxide (NO) serves as a retrograde messenger to activated neuronal NO synthase in the spinal cord via NMDA receptors (2007)
  • Author(s): Xu, L., Mabuchi, T., Katano, T., Matsumura, S., Okuda-Ashitaka, E., Sakimura, K., Mishina, M., Ito, S.
  • Journal Title: Nitric Oxide 17 Pages: 18-24
  • Peer Reviewed
• [Journal Article] Regulation of dendritogenesis via a lipid raft-associated Ca2+/calmodulin-dependent protein kinase CLICK-III/CaMKIγ (2007)
  • Author(s): Takemoto-Kimura, S., Ishihara-Ageta, N., Nonaka, M., Adachi-Morishima, A., Mano, T., Okamura, M., Fujii, H., Fuse, T., Hoshino, M., Suzuki, S., Kojima, M., Mishina, M., Okuno, H., Bito, H.
  • Journal Title: Neuron 54 Pages: 755-770
  • Peer Reviewed
• [Journal Article] Conditional gene targeting on the pure C57BL/6 genetic background (2007)
  • Author(s): Mishina, M., Sakimura, K.
  • Journal Title: Neurosci. Res. 58 Pages: 105-112
  • Peer Reviewed
• [Journal Article] Mouse liaison for integrative brain research (2007)
  • Author(s): Aiba, A., Inokuchi, K., Ishida, Y., Itohara, S., Kobayashi, K., Masu, M., Mishina, M., Miyakawa, T., Mori, H., Nakao, K., Obata, Y., Sakimura, K., Shirosihi, T., Wada, K., Yagi, T.
  • Journal Title: Neurosci. Res. 58 Pages: 103-104
  • Peer Reviewed
• [Journal Article] Enhanced cell-to-cell contacts between activated microglia and pyramidal cell dendrites following kainic acid-induced neurotoxicity in the hippocampus (2007)
  • Author(s): Hasegawa, S., Yamaguchi, M., Nagao, H., Mishina, M., Mori, K.
  • Journal Title: J. Neuroimmunol. 186 Pages: 75-85
  • Peer Reviewed
• [Journal Article] Signal pathways coupled to activation of neuronal nitric oxide synthase in the spinal cord by nociceptin/orphanin FQ (2007)
  • Author(s): Xu, L., Okuda-Ashitaka, E., Matsumura, S., Mabuchi, T., Okamoto, S., Sakimura, K., Mishina, M., Ito, S.
  • Journal Title: Neuropharmacology 52 Pages: 1318-1325
  • Peer Reviewed
• [Journal Article] Ca2+ permeability of the channel pore is not essential for theδ2 glutamate receptor channel to regulate synaptic plasticity and motor coordination (2007)
  • Author(s): Kakegawa, W., Miyazaki, T., Hirai, H., Motohashi, J., Mishina, M., Watanabe, M., Yuzaki, M.
  • Journal Title: J. Physiol. 579 Pages: 729-735
  • Peer Reviewed
• [Journal Article] Dietary restriction increases hippocampal neurogenesis by molecular mechanisms independent of NMDA receptors (2006)
  • Author(s): Kitamura, T., Mishina, M., Sugiyama, H.
  • Journal Title: Neurosci. Lett. 393 Pages: 94-96
  • Peer Reviewed
• [Journal Article] Telencephalin slows spine maturation (2006)
  • Author(s): Matsuno, H., Okabe, S., Mishina, M., Yanagida, T., Mori, K., Yoshihara, Y.
  • Journal Title: J. Neurosci. 26 Pages: 1776-1786
  • Peer Reviewed
• [Journal Article] Characterization of hippocampal theta rhythm in wild-type mice and glutamate receptor subunitδ2 mutant mice during eyeblink conditioning with a short trace interval (2005)
  • Author(s): Takatsuki, K., Kawahara, S., Mishina, M., Kirino, Y.
  • Journal Title: Brain Res. 1063 Pages: 159-167
  • Peer Reviewed
• [Journal Article] N-methyl-D-aspartate receptors play important roles in acquisition and expression of the eyeblink conditioned response in glutamate receptor subunitδ2 mutant mice (2005)
  • Author(s): Kato, Y., Takatsuki, K., Kawahara, S., Fukunaga, S., Mori, H., Mishina, M., Kirino, Y.
  • Journal Title: Neuroscience 135 Pages: 1017-1023
  • Peer Reviewed
• [Journal Article] Identification and characterization of a novel Delphilin variant with an alternative N-terminus (2005)
  • Author(s): Yamashita, T., Miyagi, Y., Ono, M., Ito, H., Watanabe, K., Sonoda, T., Tsuzuki, K., Ozawa, S., Aoki, I., Okuda, K., Mishina, M., Kawamoto, S.
  • Journal Title: Mol. Brain Res. 141 Pages: 83-95
  • Peer Reviewed
• [Journal Article] Target-cell-specific left-right asymmetry of NMDA receptor content in Schaffer collateral synapses inε1/NR2A knockout mice (2005)
  • Author(s): Wu, Y., Kawakami, R., Fukaya, M., Sakimura, K., Mishina, M., Watanabe, M., Ito, I., Shigemoto, R.
  • Journal Title: J. Neurosci. 25 Pages: 9213-9226
  • Peer Reviewed
• [Journal Article] Fyn-kinase-mediated phosphorylation of NMDA receptor NR2B subunit at Tyr 1472 is essential for maintenance of neuropathic pain (2005)
  • Author(s): Abe, T., Matsumura, S., Katano, T., Mabuchi, T., Takagi, K., Xu, L., Yamamoto, A., Hattori, K., Yagi, T., Watanabe, M., Nakazawa, T., Yamamoto, T., Sasaki, Y., Suzuki, M., Mishina, M., Nakai Y., Ito, S.
  • Journal Title: Eur. J. Neurosci. 22 Pages: 1445-1454
  • Peer Reviewed
• [Journal Article] Activation of NR2A-containing NMDA receptors is not obligatory for NMDA-receptor dependent long-term potentiation (2005)
  • Author(s): Weitlauf, C., Honse, Y., Auberson, Y.P., Mishina, M., Lovinger, D.M., Winder, D.G.
  • Journal Title: J. Neurosci. 25 Pages: 8386-8390
  • Peer Reviewed
• [Journal Article] Effect of N-methyl-D-aspartate receptorε1 subunit gene disruption of the action of general anesthetic drugs in mice (2005)
  • Author(s): Sato, Y., Kobayashi, E., Murayama, T., Mishina, M., Seo, N.
  • Journal Title: Anesthesiology 102 Pages: 557-561
  • Peer Reviewed
• [Journal Article] Defective control and adaptation of reflex eye movements in mutant mice deficient in either the glutamate receptorδ2 subunit or Purkinje cells (2005)
  • Author(s): Katoh, A., Yoshida, T., Himeshima, Y., Mishina, M., Hirano, T.
  • Journal Title: Eur. J. Neurosci. 21 Pages: 1315-1326
  • Peer Reviewed
• [Journal Article] Role of hippocampal NMDA receptors in trace eyeblink conditioning (2005)
  • Author(s): Sakamoto, T., Takatsuki, K., Kawahara, S., Kirino, Y., Niki, H., Mishina, M.
  • Journal Title: Brain Res. 1039 Pages: 130-136
  • Peer Reviewed
• [Journal Article] Control of synaptic connection by glutamate receptorδ2 in the adult cerebellum (2005)
  • Author(s): Takeuchi, T., Miyazaki, T., Watanabe, M., Mori, H., Sakimura, K., Mishina, M.
  • Journal Title: J. Neurosci. 25 Pages: 2146-2156
  • Peer Reviewed
• [Journal Article] Rescue of abnormal phenotypes of theδ2 glutamate receptor-null mice by mutantδ2 transgenes (2005)
  • Author(s): Hirai, H., Miyazaki, T., Kakegawa, W., Matsuda, S., Mishina, M., Watanabe, M., Yuzaki, M.
  • Journal Title: EMBO Reports 6 Pages: 90-95
  • Peer Reviewed