競合的シナプス回路成熟の構造基盤と分子基盤

2005 Fiscal Year Annual Research Report

• Project/Area Number: 17023001
• Research Institution: Hokkaido University
• Principal Investigator: 渡辺 雅彦 北海道大学, 大学院・医学研究科, 教授 (70210945)
• Keywords: グルタミン酸受容体 / セレベリン / GluRd2 / シナプス形成 / 小脳 / プルキンエ細胞 / 遺伝子ノックアウトマウス

Research Abstract

プルキンエ細胞は、近位樹状突起を1本の登上線維が単一支配し、遠位樹状突起を約10万本の平行線維が支配するという、特徴的なシナプス回路を作り上げている。グルタミン酸受容体δ2は平行線維シナプスに選択的で、この分子完全欠失型欠損によりプルキンエ細胞と平行線維終末間のシナプス結合が弱まり、多数のフリースパインが出現することが知られている。本年度の研究推進により、この平行線維シナプス形成の分子機構に関する以下の研究成果が得られた。
正常なシナプス回路が完成した成体期において、δ2欠失を誘導する条件的欠損マウスを作成し、その後の変化を形態学的に追求した。その結果、この分子の減少と一致して、平行線維シナプスが減少し多数のフリースパインが生じた(Takeuchi, Miyazaki et al., J.Neuroscience,25:2146-2156,2005)。この結果は、δ2が発生期だけではなく成体期における平行線維シナプスの維持に関わっていることを示している。さらに、セレベリン1は小脳顆粒細胞に選択的な分泌性分子であるが、この分子欠損においても同様の平行線維シナプス形成障害が起こった(Hirai et al., Nature Neuroscience, 8:1534-1541,2005)。従って、これら2つの分子機構が協同して、‘平行線維シナプスの強化と維持'に関与していることが明らかとなった。

Research Products

• [Journal Article] Impaired cerebellar functions in mutant mice lacking DNER. (2006)
  • Author(s): Tohgo, A., Eiraku, M., Miyazaki, T., Miura, E., Ono, K., Kawaguchi, S., Nishi, M., Watanabe, M., Hirano, T., Kengaku, M., Takeshima, H.
  • Journal Title: Mol.Cell.Neurosci. (in press)
• [Journal Article] Complementary stripes of phospholipase Cβ3 and Cβ4 expression by Purkinje cell subsets in the mouse cerebellum. (2006)
  • Author(s): Sarna, J.T., Marzban, H., Watanabe, M., W, Hawkes, R.
  • Journal Title: J.Comp.Neurol. (in press)
• [Journal Article] Improved methods for ultracryotomy of CNS tissue for ultrastructural and immunogold analyses. (2006)
  • Author(s): AKagi, T., Ishida, K., Hanasaka, T., Hayashi, S., Watanabe, M., Hashikawa, T., Tohoyama, K.
  • Journal Title: J.Neurosci.Methods (in press)
• [Journal Article] Maintenance of presynaptic function by AMPA receptor-mediated excitatory postsynaptic activity in adult brain. (2006)
  • Author(s): Kakizawa, S., Miyazaki, T., Iino, M., Watanabe, M., Kano, M.
  • Journal Title: Proc.Natl.Acad.Sci.USA (in press)
• [Journal Article] Rescue of abnbormal phenotypes of the δ2 glutamate receptor-null mice by mutant δ2 transgenes. (2005)
  • Author(s): Hirai, H., Miyazaki, T., Kakegawa, W., Matsuda S., Mishina, M., Watanabe, M., Yuzaki, M.
  • Journal Title: EMBO report 6 Pages: 90-95
• [Journal Article] Retinotectal transmission in the optic tectum of rainbow trout. (2005)
  • Author(s): Kinosnita, M., Fuyaka M., Tojima, T., Kojima, S., Ando, H., Watanabe, M., Urano, A., Ito, E.
  • Journal Title: J.Comp.Neurol. 484 Pages: 249-259
• [Journal Article] Evidence for creatine biosynthesis in Muller glia. (2005)
  • Author(s): Nakashima, T., Tomi, M., Tachikawa M., Watanabe M., Terasaki, T., Hosoya, K.
  • Journal Title: Glia 52 Pages: 47-52
• [Journal Article] NR2-to-NR3B subunit conversion of NMDA receptor in early postnatal motoneurons. (2005)
  • Author(s): Fukaya M.Hayashi, Y., Watanabe, M.
  • Journal Title: Eur.J.Neurosci. 21 Pages: 1432-1436
• [Journal Article] Control of synaptic connection by glutamate receptor δ2 in the mature cerebellum. (2005)
  • Author(s): Takeuchi, T., Miyazaki T., Watanabe M., Mori, H., Sakimura, K., Mishina, M.
  • Journal Title: J.Neurosci. 25 Pages: 2143-2156
• [Journal Article] Differential roles of glial and neuronal glutamate transporters in Purkinje cell synapses. (2005)
  • Author(s): Taxayasu Y., Iino, M., Kakegawa, W., Maeno, H., Watase, K., Wada K., Miyazaki, T., Watanabe, M., Tanaka, K., Ozawa, S.
  • Journal Title: J.Neurosci. 25 Pages: 8788-8793
• [Journal Article] Identification and characterization of a novel member of murine semaphorin family. (2005)
  • Author(s): Taniguchi M., Masuda, T., Fukaya, M., Kataoka, H., Mishina, M.Yaginuma, H., Watanabe, M., Shimizu, T.
  • Journal Title: Genes to Cells 10 Pages: 785-792
• [Journal Article] Ptfla, a bHLH transcriptional gene, defines GABAergic neuronal fates in cerebellum. (2005)
  • Author(s): Hoshino, M., Nakamura, S., Mori, K., Kawauchi, T., Terao, M., Nishimura, Y.V., Fukuda, A., Fuse, T., Matsuo, N., Sone, M., Watanabe, M., Bito, H., Terashima, T., Wright, C.V.E., Kawaguchi, Y., Nakao, K., Nabeshima, Y.
  • Journal Title: Neuron 47 Pages: 201-213
• [Journal Article] Distinct spatio-temporal expression of ABCA and ABCG transporters in the developing and adult mouse brain. (2005)
  • Author(s): Tachikawa, M., Watanabe, M., Hori, S., Fukaya, M., Ohtsuki, S., Asashima1, T., Terasaki, T.
  • Journal Title: J.Neurochem. 95 Pages: 294-304
• [Journal Article] Autoantibodies and cell-mediated autoimmunity to NMDA-type GluTe2 in patients with Rasmussen's encephalitis and chronic progressive epilepsia partialis continua. (2005)
  • Author(s): Takahashi, Y., Mori, H.Mishina, M., Watanabe, M., Kondo, N., Shomomura, J., Kubota, Y., Matsuda, K., Fukushima, K., Shiroma, M., Akasaka, N., Nishida, H., Imamura, A., Watanabe, H., Sugiyama, N., Ikezawa, M., Fujiwara, T.
  • Journal Title: Epilepsia 46 Pages: 152-158
• [Journal Article] Fyn kinase-mediated phosphorylation of NMDA receptor NR2B subunit at Tyr1472 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., Mishina, M., Nakai, Y., Ito, S.
  • Journal Title: Eur.J.Nerosci. 22 Pages: 1445-1455
• [Journal Article] Target-cell-specific left-right asymmetry of NMDA receptor content in Schaffer collateral synapses in ε1/NR2A knock-out 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
• [Journal Article] Spatial diversity in gene expression for VDCCγ subunit family in developing and adult mouse brains. (2005)
  • Author(s): Fukaya, M.Yamazaki, M., Sakimura, K., Watanabe, M.
  • Journal Title: Neurosci.Res. 53 Pages: 376-383
• [Journal Article] Complementary roles of cholecystokinin and parvalbumin expressing GABAergic neurons in hippocampal network oscillations. (2005)
  • Author(s): Klausberger, T., Marton, L.F., O'Neill, J., Huck, J.H.J., Dalezios, Y., Fuentealba, P., Suen, W.-Y, Papp, E., Kaneko T., Watanabe, M., JCsicsvari, J., Somogyi, P.
  • Journal Title: J.Neurosci. 25 Pages: 9782-9793
• [Journal Article] Clbn1 is essential for synaptic integrity and information processing in the cerebellum. (2005)
  • Author(s): 6.Hirai, H., Pang, Z., Bao, D., Miyazaki, T., Li, L., Parris, J., Rong, Y., Watanabe, M., Yuzaki, M., Morgan, J.I.
  • Journal Title: Nature Neurosci. 8 Pages: 1534-1541
• [Journal Article] Cellular distribution of glutamate transporters in the gastrointestinal tract of mice. An immunohistochemical and in situ hybridization approach. (2005)
  • Author(s): Iwanaga, T., Goto, M., Watanabe, M.
  • Journal Title: Biomed.Res. 26 Pages: 271-278