Elucidation of mechanisms underlying involvement of neurotrophic factors in visual cortical plasticity using RNA interference

• Project/Area Number: 19300117
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: TSUMOTO Tadaharu The Institute of Physical and Chemical Research, 津本研究ユニット, ユニットリーダー (50028619)
• Co-Investigator(Kenkyū-buntansha): SOHYA Kazuhiro 独立行政法人理化学研究所, 津本研究ユニット, 研究員 (80415207) ; JIANG Bin 独立行政法人理化学研究所, 津本研究ユニット, 訪問研究員 (30446520) ; AKANEYA Yukio 大阪大学, 医学系研究科, 助教 (40222517) ; KAMEYAMA Katsuro 独立行政法人理化学研究所, 津本研究ユニット, 訪問研究員 (80446517)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2008: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2007: ¥11,960,000 (Direct Cost: ¥9,200,000、Indirect Cost: ¥2,760,000)
• Keywords: 脳 / シナプス / 可塑性 / 大脳皮質 / 視覚野 / 発達 / 神経

Research Abstract

研究成果の概要:大脳皮質視覚野で片目遮蔽後にみられる両眼反応性変化やシナプス長期増強(LTP)は発達脳可塑性の代表的な例として古くより研究されてきたが、従来の方法では種々の限界があった。本研究は、新しく開発されたRNA干渉法をマウス脳に適用し、視覚野可塑性のメカニズム解明をめざした。
まず、脳由来神経栄養因子(BDNF)の発現を抑えるsmall interfering RNA (siRNA) を使い、BDNFの発現を抑えた視覚野標本の作製を試みた。その結果、使用した電気穿孔法では siRNA が十分に視覚野ニューロンに入らずBDNFの発現を完全に抑えることができなかった。しかし、薬理学的方法で代謝型グルタミン酸受容体(mGluR5)がLTP誘発に関与していることを発見し、さらに、mGluR5の活性化によって生じた内因性カンナビノイドが視覚野の可塑性に関与しているという予想外の知見を得た。

Research Products

• [Journal Article] Roles of endocannabinoids in heterosynaptic long-term depression of excitatory synaptic transmission in visual cortex of young mice (2008)
  • Author(s): Huang, Y., Yasuda, H., Sarihi, A. and Tsumoto, T.
  • Journal Title: J. Neurosci. 28 Pages: 7074-7083
  • Peer Reviewed
• [Journal Article] Regulation of excitability and plasticity by endocannabinoids and PKA in developing hippocampus (2008)
  • Author(s): Yasuda, H., Huang, Y. and Tsumoto, T.
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 3106-3111
  • Peer Reviewed
• [Journal Article] Metabotropic glutamate receptor type 5-dependent long-term poptentiation of excitatory synapses on fast-spiking GABAergic neurons in mouse visual cortex (2008)
  • Author(s): Sarihi, A., Jiang, B., Komaki, A-R., Sohya, K., Yanagawa, Y. and Tsumoto, T.
  • Journal Title: J. Neurosci. 28 Pages: 1224-1235
  • Peer Reviewed
• [Journal Article] Metabotropic glutamate receptor type 5-dependent long-term poptentiation of excitatory synapses on fast-spiking GABAergic neurons in mouse visual cortex (2008)
  • Author(s): Sarihi A, Jiang B, Komaki A-R, Sohya K, Yanagawa Y, Tsumoto T.
  • Journal Title: Journal of Neuroscience 28 Pages: 1224-1235
  • Peer Reviewed
• [Journal Article] Roles of endocannabinoids in heterosynaptic long-term depression of excitatory synaptic transmission in visual cortex of young mice (2008)
  • Author(s): Huang Y, Yasuda H, Sarihi A, Tsumoto T
  • Journal Title: Journal of Neuroscience 28 Pages: 7074-7083
  • Peer Reviewed
• [Journal Article] Regulation of excitability and plasticity by endocannabinoids and PKA in developing hippocampus (2008)
  • Author(s): Yasuda H, Huang Y, Tsumoto T.
  • Journal Title: Proc. Natl. Acad. Sci. USA 105 Pages: 3106-3111
  • Peer Reviewed
• [Journal Article] Metabotropic glutamate receptor type 5-dependent long-term potentiation of excitatory synapses on fast-spiking GABAergic neurons in mouse visual cortex. (2008)
  • Author(s): Sarihi, A., Jiang, B., Komaki, A-R-., Sohya, K., Yanagawa, Y., Tsumoto, T.
  • Journal Title: Journal of Neuroscience 28 Pages: 1224-1235
  • Peer Reviewed
• [Journal Article] A local reduction in cortical GABAergic synapses following a loss of endogenous BDNF, as revealed by single-cell gene knockout method (2007)
  • Author(s): Kohara, K., Yasuda, H., Huang, Y., Adachi, N., Sohya, K. and Tsumoto, T.
  • Journal Title: J. Neurosci. 27 Pages: 7234-7244
  • Peer Reviewed
• [Journal Article] GABAergic neurons are less selective to stimulus orientation than excitatory neurons in layer II/III of visual cortex, as revealed by in vivo functional Ca2+ imaging in transgenic mice (2007)
  • Author(s): Sohya K., Kameyama K., Yanagawa Y., Obata K. and Tsumoto T
  • Journal Title: J. Neurosci. 27 Pages: 2145-2149
  • Peer Reviewed
• [Journal Article] GABAergic neurons are less selective to stimulus orientation than excitatory neurons in layer II/III of visual cortex,as revealed by in vivo functional Ca^<2+>imaging in tramsgenic mice. (2007)
  • Author(s): Sohya K., Kameyama K., Yanagawa Y., Obata K., Tsumoto T
  • Journal Title: Journal of Neuroscience 27 Pages: 2145-2149
  • Peer Reviewed
• [Journal Article] A local reduction in cortical GABAergic synapses following a loss of endogenous BDNF,as revealed by single-cell gene knockout method. (2007)
  • Author(s): Kohara, K., Yasuda, H., Huang Y., Adachi, N., Sohya, K., Tsumoto, T.
  • Journal Title: Journal of Neuroscience 27 Pages: 7234-7244
  • Peer Reviewed
• [Presentation] Activity-dependent trafficking of BDNF in axons of cortical neurons and an antagonizing action on endocannabinoid- mediated suppression of transmitter release at presynaptic sites (2008)
  • Author(s): Tsumoto T.
  • Organizer: 6^<th> FENS Forum of European Neuroscience
  • Place of Presentation: Geneva, Switzerland
  • Year and Date: 2008-07-13
• [Presentation] Activity-dependent trafficking of BDNF in axons of cortical neurons and an antagonizing action on endocannabinoid-mediated suppression of transmitter release at presynaptic sites (2008)
  • Author(s): Tsumoto T
  • Organizer: 6th FENS Forum of European Neuroscience
  • Place of Presentation: ジュネーブ、スイス
  • Year and Date: 2008-07-13
• [Presentation] LTP of excitatory synapses on GABAergic neurons in mouse visual cortex: Its mechanism different from that of excitatory synapses on pyramidal neurons (2008)
  • Author(s): Tsumoto T.
  • Organizer: 8^<th> Biennial Meeting of Asia-Pacific Society for Neurocehmistry
  • Place of Presentation: Shanghai, China
  • Year and Date: 2008-06-23
• [Presentation] Imaging in two worlds: Trafficking molecules in vitro and activities of different neurons in vivo (2007)
  • Author(s): Tsumoto T.
  • Organizer: International Symposium "Topical Problems of Biophotonics-2007"
  • Place of Presentation: Nizhny Novgorod, Russia
  • Year and Date: 2007-08-04
• [Presentation] Different visual response properties between excitatory and inhibitory neurons in mouse visual cortex,as revealed by in vivo two-photon functional calium imaging (2007)
  • Author(s): Kameyama, K.
  • Organizer: 7^<th> IBRO World Congress
  • Place of Presentation: メルボルン、オーストラリア
  • Year and Date: 2007-08-02
• [Presentation] Trafficking of BDNF in axons and dendrites of cortical neurons, analyzed by live-cell imaging (2007)
  • Author(s): Tsumoto T, Adachi N.
  • Organizer: 7^<th> IBRO World Congress of Neuroscience
  • Place of Presentation: Melbourne, Australia
  • Year and Date: 2007-07-14
• [Remarks] ホームページ等
  • URL: http://tsumoto.brain.riken.jp/
• [Remarks]
  • URL: http://tsumoto.brain.riken.jp
• [Remarks]
  • URL: http://tsumoto.brain.riken.jp/