Analysis of specific neural pathway using double viral vector system

• Project/Area Number: 25560436
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Brain biometrics
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: KOBAYASHI Kenta 生理学研究所, 脳機能計測・支援センター, 准教授 (70315662)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
• Keywords: Rho GTPase / Rho-kinase / ウイルスベクター / 皮質線条体ニューロン / アポトーシス / Rhoファミリー / 大脳皮質 / 線条体 / 大脳皮質ニューロン / レンチウイルスベクター / アデノ随伴ウイルスベクター / Cre-loxP / 大脳基底核

Outline of Final Research Achievements

Brain functions are controlled by the complicated neural circuit. In order to understand brain functions, we need to analyze each specific neural pathway, a component of the neural circuit. Rho GTPase signaling pathway via Rho-kinase, one of the major effector molecules of Rho, is becoming increasingly clear to regulate various neuronal functions. In the present study, by using a dual viral vector approach combining a neuron-specific retrograde gene transfer lentiviral vector and an adeno-associated virus vector, we demonstrated that the Rho/Rho-kinase signaling pathway was essential for the survival of cortical neurons forming the corticostriatal pathway.

Research Products

• [Journal Article] Altering Entry Site Preference of Lentiviral Vectors into Neuronal Cells by Pseudotyping with Envelope Glycoproteins. (2016)
  • Author(s): Kobayashi K, Kato S, Inoue K, Takada M, Kobayashi K.
  • Journal Title: Methods Mol Biol. Volume: 1382: Pages: 175-86
  • DOI: 10.1007/978-1-4939-3271-9_12
  • ISBN: 9781493932702, 9781493932719
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Phosphoproteomics of the Dopamine Pathway Enables Discovery of Rap1 Activation as a Reward Signal In Vivo (2016)
  • Author(s): Nagai T, Nakamuta S, Kuroda K, Nakauchi S, Nishioka T, Takano T, Zhang X, Tsuboi D, Funahashi Y, Nakano T, Yoshimoto J, Kobayashi K, Uchigashima M, Watanabe M, Miura M, Nishi A, Kobayashi K, Yamada K, Amano M, Kaibuchi K
  • Journal Title: Neuron Volume: 89 (3) Issue: 3 Pages: 550-65
  • DOI: 10.1016/j.neuron.2015.12.019
  • Peer Reviewed / Open Access
• [Journal Article] Asynchronous therapy restores motor control by rewiring of the rat corticospinal tract after stroke. (2014)
  • Author(s): Wahl AS, Omlor W, Rubio JC, Chen JL, Zheng H, Schroter A, Gullo M, Weinmann O, Kobayashi K, Helmchen F, Ommer B, Schwab ME
  • Journal Title: Science Volume: 344 Issue: 6189 Pages: 1250-1255
  • DOI: 10.1126/science.1253050
  • Peer Reviewed
• [Journal Article] Improved transduction efficiency of a lentiviral vector for neuron-specific retrograde gene transfer by optimizing the junction of fusion envelope glycoprotein. (2014)
  • Author(s): Kato, S., Kobayashi, K., and Kobayashi, K.
  • Journal Title: J Neurosci. Methods Volume: 227 Pages: 151-158
  • DOI: 10.1016/j.jneumeth.2014.02.015
  • Peer Reviewed
• [Journal Article] Viral vector-mediated selective and reversible blockade of the pathway for visual orienting in mice. (2013)
  • Author(s): Sooksawate T, Isa K, Matsui R, Kato S, Kinoshita M, Kobayashi K, Watanabe D, Kobayashi K, Isa T.
  • Journal Title: Frontiers in Neural Circuits Volume: 7 Pages: 162-162
  • DOI: 10.3389/fncir.2013.00162
  • Peer Reviewed
• [Journal Article] Highly efficient retrograde gene transfer into motor neurons by lentiviral vector pseudotyped with fusion glycoprotein. (2013)
  • Author(s): Hirano et al.
  • Journal Title: PLos One Volume: 8 Issue: 9 Pages: e75896-e75896
  • DOI: 10.1371/journal.pone.0075896
  • Peer Reviewed
• [Journal Article] Dissecting circuit mechanisms by genetic manipulation of specific neural pathways. (2013)
  • Author(s): Kato et al.
  • Journal Title: Rev. Neurosci. Volume: 24 Issue: 1 Pages: 1-8
  • DOI: 10.1515/revneuro-2012-0043
  • Peer Reviewed
• [Presentation] Survival of Corticostriatal Neurons by Rho GTPase signaling pathway (2015)
  • Author(s): Kenta Kobayashi
  • Organizer: Neuroscience 2015
  • Place of Presentation: Chicago, United States of America
  • Year and Date: 2015-10-18
  • Int'l Joint Research
• [Presentation] ウイルスベクターを利用した脳機能解析 (2014)
  • Author(s): 小林憲太
  • Organizer: 第24回日本臨床精神神経薬理学会・第44回日本神経精神薬理学会 合同年会
  • Place of Presentation: 愛知県 名古屋市 名古屋国際会議場
  • Year and Date: 2014-11-20 – 2014-11-22
  • Invited
• [Presentation] Functional analysis of Rho GTPase signaling in specific neuronal pathway using newly developed genetic manipulation technology (2014)
  • Author(s): Kenta Kobayashi, Shigeki Kato, Kozo Kaibuchi, Kazuto Kobayashi
  • Organizer: 9th FENS Forum of Neuroscience
  • Place of Presentation: イタリア ミラノ市 MiCo - Milano Congressi
  • Year and Date: 2014-07-05 – 2014-07-09
• [Presentation] Functional analysis of Rho GTPase signaling in specific neuronal pathway (2013)
  • Author(s): Kenta Kobayashi, Shigeki Kato, Kozo Kaibuchi, Kazuto Kobayashi
  • Organizer: 第36回日本神経科学大会
  • Place of Presentation: 京都府京都市 国立京都国際会館
• [Book] 実験医学 (2015)
  • Author(s): 小林憲太
  • Total Pages: 153
  • Publisher: 羊土社
• [Book] In Gene Therapy-Tools and Potential Applications (2013)
  • Author(s): Kato S, Kobayashi K, Inoue K, Takada M, Kobayashi K
  • Publisher: InTech Press
• [Remarks] ウイルスベクター開発室 - 生理学研究所
  • URL: http://www.nips.ac.jp/research/group/post-30/
• [Remarks] ウイルスベクター開発室ー生理学研究所
  • URL: http://www.nips.ac.jp/research/group/post-30/