異種シナプス間競合原理に基づく小脳神経回路発達の分子機構

2004 Fiscal Year Annual Research Report

• Project/Area Number: 14208091
• 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)
• Co-Investigator(Kenkyū-buntansha): 深谷 昌弘 北海道大学, 大学院・医学研究科, 助手 (10360900) ; 狩野 方伸 金沢大学, 大学院・医学研究科, 教授 (40185963)
• Keywords: 小脳 / プルキンエ細胞 / シナプス形成 / 平行線維 / 登上線維 / グルタミン酸受容体 / 発達 / 遺伝子改変マウス

Research Abstract

プルキンエ細胞に対する平行線維と登上線維によるシナプス回路発達の過程は、回路発達研究に最も適したモデル系のひとつである。平行線維シナプスに選択的なグルタミン酸受容体δ2の遺伝子ノックアウトマウスの解析から、この分子が平行線維シナプス側の強化分子として機能し、その欠失により平行線維終末とプルキンエ細胞スパインの間のシナプス結合率が低下しフリースパインが生じることを見い出した(Kurihara et al.,1997,J.Neurosci.17:9613-9623:下図参照)。
今回、平行線維支配の弱まった環境において、もう一つの入力線維である登上線維支配がどのように変化していることを神経トレーサー標識、蛍光多重染色、電顕解析法などを用いて解析した。その結果、遠位樹状突起に出現したフリースパインを目がけて、登上線維支配の遠位拡大が生じ、これが周囲のプルキンエ細胞に及ぶことにより登上線維による多重支配が生じた(Hahimoto et al.,2001;J.Neurosci.21:9701-9712;Ichikawa et al.,2002,J.Neurosci.22:8487-8503)。これらの事実は、プルキンエ細胞のシナプス回路が異種入力線維間の競合を基盤として樹状突起に対するドメイン的支配が確立し、ここでδ2が平行線維シナプス側の強化分子機構として機能していることを示している。同時に、登上線維側にも強化分子機構が存在し、δ2と拮抗する形で平行線維支配の過度な近位化(拡大化)を防いでいる可能性をも示唆する。その拮抗分子機構が、P/Q型カルシウムチャネルがその役割を担っていることも明らかすることができた(Miyazaki et al.,2004,J.Neurosci.24:1734-1743)。

Research Products

• [Journal Article] P/Q-type Ca^<2+> channel α1A regulates synaptic competition on developing cerebellar Purkinje cells (2004)
  • Author(s): Miyazaki, M., Hashimoto, K., Shin H.-S., Kano, M., Watanabe, M.
  • Journal Title: J.Neurosci. 24 Pages: 1734-1743
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Targeted disruption of the mouse 3-phosphoglycerate dehydrogenase gene causes severe neurodevelopmental defects and results in embryonic lethality. (2004)
  • Author(s): Yoshida, K., Furuya, S., Osuka, S., Mitoma, J., Shinoda, Y., Watanabe, M., Azuma, N., Tanaka, H., Hashikawa, T., Itohara, S., Hirabayashi, Y.
  • Journal Title: J.Biol.Chem. 279 Pages: 3573-3577
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Two distinct classes of muscarinic action on hippoccampal inhibitory synapses : M2-mediated direct suppression and M1/M3-mediated indirect suppression through endocannabinoid signaling. (2004)
  • Author(s): Fukudome, Y., Ohno-Shosaku, T., Matsui, M., Omori, Y., Fukaya, M., Taketo, M., Watanabe, M., Manabe, M., Kano, M.
  • Journal Title: Eur.J.Neurosci. 19 Pages: 2682-2692
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Blood-to-retina transport of creatine via creatine transporter (CRT) at the rat inner blood-brain barrier. (2004)
  • Author(s): Nakashima, T., Tomi, M., Katayama, K., Tachikawa, M., Watanabe, M., Terasaki, T., Hosoya, K.
  • Journal Title: J.Neurochem. 89 Pages: 1454-1461
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Immunolocalization of metabotropic glutamate receptor 1a (mGluR1a) in distinct classes of interneuron in the CA1 region of the rat hippocampus. (2004)
  • Author(s): Ferraguti, F., Cobden, P., Pollard, M., Cope, D., Shigemoto, R., Watanabe, M., Somogy, P.
  • Journal Title: Hippocampus 14 Pages: 193-215
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Widespread expression of the AMPA receptor GluR2 subunit at glutamatergic synapses in the rat spinal cord and phosphorylation of GluR1 in response to noxious stimulation revealed with an antigen unmasking (2004)
  • Author(s): Nagy, G.G., Al-Ayyan, M., Andrew, D., Fukaya, M., Watanabe, M., Todd, A.J.
  • Journal Title: J.Neurosci. 24 Pages: 5766-5777
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] NMDA Receptor GluRe/NR2 subunits are essential for postsynaptic localization and protein stability of GluRz1/NR1 subunit. (2004)
  • Author(s): Abe, M., Fukaya, M., Yagi, T., Mishina, M., Watanabe, M., Sakimura, K.
  • Journal Title: J.Neurosci. 24 Pages: 9292-9304
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1. (2004)
  • Author(s): Hama, K., Aoki, J., Fukaya, M., Kishi, Y., Sakai, T., Suzuki, R., Ohta, H., Yamori, T., Watanabe, M., Chun, J., Arai, H.
  • Journal Title: J.Biol.Chem. 279 Pages: 17634-17639
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Changes of high-affinity choline transporter expression during degeneration and regeneration of hypoglossal nerves in mice. (2004)
  • Author(s): Oshima, S., Yamada, K., Shirakawa, T., Watanabe, M.
  • Journal Title: Neurosci.Lett. 97 Pages: 97-101
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Functional expression of rat ABCG2 and its enhancement by astrocyte-derived soluble factor(s). (2004)
  • Author(s): Hori, S., Ohtsuki, S., Tachikawa, M., Kimura, N., Kondo, T., Watanabe, M., Nakashima, E., Terasaki, T.
  • Journal Title: J.Neurochem. 90 Pages: 526-536
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Defective function of GABA-containing synaptic vesicles in mice lacking the AP-3B cclathrin adaptor. (2004)
  • Author(s): Nakatsu, F., Okada, M., Mori, F., Kamazawa, N., Iwasa, H., Zhu, G., Kasagi, Y., Kamiya, H., Harada, A., Nishimura, K., Takeuchi, A., Miyazaki, T., Watanabe, M., Yuasa, S., Manabe, T., Wakabayashi, K., Kaneko, S., Saito, T., Ohno, H.
  • Journal Title: J.Cell Biol. 167 Pages: 293-302
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Upreguration of GluR2 decrease intracellular Ca2+ following ischemia in developing gerbils. (2004)
  • Author(s): Oguro, K., Miyawaki, T., Yokota, H., Kato, K., Kamiya, T., Katayama, Y., Fukaya, M., Watanabe, M., Shimazaki, K.
  • Journal Title: Neurosci.Lett. 364 Pages: 101-105
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Mammalian septin Sept2 modulates the activity of GLAST, a glutamate transporter in astrocytes. (2004)
  • Author(s): Kinoshita, N., Kimura, K., Matsumoto, N., Watanabe, M., Fukaya, M., Ide, C.
  • Journal Title: Genes Cells 9 Pages: 1-14
• [Journal Article] GABAergic basket cells expressing cholecystokinin contain vesicular glutamate transporter type 3 (VGLUT3) in their synaptic terminals in hippocampus and isocortex of the rat. (2004)
  • Author(s): Somogyi, J., Baude, A., Omori, Y., Shimizu, H., Mestikawy, S.E., Fukaya, M., Ryuichi, S., Watanabe, M., Somogyi, P.
  • Journal Title: Eur.J.Neurosi. 19 Pages: 552-569
• [Journal Article] Distinct cellular expression of creatine synthetic enzyme GAMT and creatine kinases uCK-Mi and CK-B suggest novel neuron-glial relationship for brain energy homeostasis. (2004)
  • Author(s): Tachikawa, M., Fukaya, M., Terasaki, T., Ohtsuki, S., Watanabe, M.
  • Journal Title: Eur.J.Neurosci. 20 Pages: 144-160
• [Journal Article] Identification and characterization of novel developmentally regulated neural-specific proteins, BRINP family. (2004)
  • Author(s): Kawano H, Nakatani T, Mori T, Ueno S, Fukaya M, Abe A, Kobayashi M, Toda F, Watanabe M, Matsuoka I.
  • Journal Title: Mol Brain Res. 128 Pages: 60-75
• [Journal Article] Age-dependent enhancement of hippocampal long-term potentiation in knock-in mice expressing human apoliporotein E4 instead of mouse apoliporotein E. (2004)
  • Author(s): Kitamura, H.W., Hamanaka, H., Watanabe, M., Wada, K., Yamazaki, C., Fujita, S.C., Manabe, T., Nukina, N.
  • Journal Title: Neurosci.Lett. 369 Pages: 173-178
• [Journal Article] Signaling complex formation of phospholipase Cb4 with mGluR1a and IP3 R1 at the perisynapse and endoplasmic reticulum in the mouse brain. (2004)
  • Author(s): Nakamura, M., Sato, K., Fukaya, M., Araishi, K., Aiba, A., Kano, M., Watanabe, M.
  • Journal Title: Eur.J.Neurosci 20 Pages: 2929-2944
• [Journal Article] A novel action of stargazin as an enhancer of AMPA receptor activity.
  • Author(s): Yamazaki, M., Ohno-Shosaku, T., Fukaya, M., Kano, M., Watanabe, M., Sakimura, K.
  • Journal Title: Neurosci.Res. 印刷中
• [Journal Article] Synaptic distribution of the NR1, NR2A, and NR2B subunits of the NMDA receptor in the rat lumbar spinal cord revealed with an antigen unmasking technique
  • Author(s): Nagy, G.G., Watanabe, M., Fukaya, M., Todd, R.
  • Journal Title: Eur.J.Neurosci 印刷中
• [Journal Article] The delta2 "glutamate receptor is not activated by glutamate-like ligand.
  • Author(s): Hirai, H., Miyazaki, T., Mishina, M., Watanabe, M., Yuzaki, M.
  • Journal Title: EMBO report 印刷中
• [Journal Article] Evidence for creatine biosynthesis in Muller glial cells.
  • Author(s): Nakashima, T., Tomi, M., Tachikawa, M., Watanabe, M., Terasaki, T., Hosoya, K.
  • Journal Title: J.Neurochem 印刷中
• [Journal Article] NR2-to-NR3B subunit conversion of NMDA receptor in early postnatal motoneurons.
  • Author(s): Fukaya, M., Hayashi, Y., Watanabe, M.
  • Journal Title: Eur.J.Neurosci 印刷中
• [Journal Article] Control of synaptic connection by glutamate receptor d2 in the mature cerebellum.
  • Author(s): Takeuchi, T., Miyazaki, T., Watanabe, M., Mori, H., Sakimura, K., Mishina, M.
  • Journal Title: J.Neurosci. 印刷中