Development of genetic manipulation technology for excitatory and inhibitory control of the target neuron activity

• Project/Area Number: 22650065
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Neuroscience in general
• Research Institution: Fukushima Medical University
• Principal Investigator: KOBAYASHI Kazuto 福島県立医科大学, 医学部, 教授 (90211903)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥2,630,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,200,000 (Direct Cost: ¥1,200,000)
• Keywords: 脳機能 / 神経活動 / 細胞標的法 / 抗体 / リポソーム / プロテオリポソーム

Research Abstract

In the present study, we aimed to develop a novel technology for excitatory and inhibitory control of the activity of target neuronal types. A single chain variable region of anti-Tac monoclonal antibody against human interleukin-2 receptor a-subunit was fused to Fc fragment[anti-Tac(Fv)-Fc] was bound to liposome to produce immunoliposome. Anti-Tac(Fv) was connected to the transmembrane domain of vesicular somatitis virus glycoprotein or VSV-G[anti-Tac(Fv)-VSV-G], and anti-Tac(Fv)-VSV-G was expressed in insect cells by the baculoviral vector system. These cells were fused to loposome to generate proteoliposome containing anti-Tac(Fv)-VSV-G. We succeeded in the reduction of nonspecific binding of immunoliposome and proteoliposome by adding unlabelled control liposome into the solution containing the rhodamine-labelled liposome. This strategy will be useful to control the activity of neurons by introducing some drugs that inhibit ion channels into immunoliposome or proteoliposome.

Research Products

• [Journal Article] Selective neural pathway targeting reveals key roles of thalamostriatal projection in the control of visual discrimination (2011)
  • Author(s): Kato, S., Kuramochi, M., Kobayashi, K., Fukabori, R., Okada, K., Uchigashima M., Watanabe, M., Tsutsui, Y., and Kobayashi, K.
  • Journal Title: J. Neurosci Volume: 31(47) Pages: 17169-171791
  • Peer Reviewed
• [Journal Article] Sensory input regulates spatial and subtype-specific patterns of neuronal turnover in the adult olfactory bulb (2011)
  • Author(s): Sawada, M., Kaneko, N., Wake, H., Inada, H., Kato, Y., Yanagawa, Y., Kobayashi, K., Nemoto, T., Nabekura, J. and Sawamoto, K.
  • Journal Title: J. Neurosci Volume: 31(32) Pages: 11587-11596
  • Peer Reviewed
• [Journal Article] Postnatal development of tyrosine hydroxylasem RNA-expressing neurons in mouse neostriatum (2011)
  • Author(s): Masuda, M., Miura, M., Inoue, R., Imanishi, M., Saino-Saito, S., Takada, M., Kobayashi, K., and Aosaki, T.
  • Journal Title: Eur. J. Neurosci Volume: 34(9) Pages: 1355-13671
  • Peer Reviewed
• [Journal Article] A lentiviral strategy for highly efficient retrograde gene transfer by pseudotyping with fusion envelope glycoprotein (2011)
  • Author(s): Kato, S., Kobayashi, K., Inoue, K., Kuramochi, M., Okada, T., Yaginuma, H., Morimoto, K., Shimada, T., Takada, M., and Kobayashi, K.
  • Journal Title: Hum. Gene Ther Volume: 22(2) Pages: 197-206
  • Peer Reviewed
• [Journal Article] Rho/Rho-kinase signaling controls axon patterning of a specified subpopulation of cranial motor neurons (2011)
  • Author(s): Kobayashi, K., Masuda, T., Takahashi, M., Miyazaki, J., Nakagawa, M., Uchigashima, M., Watanabe, M., Yaginuma, H., Osumi, N., Kaibuchi, K., and Kobayashi, K.
  • Journal Title: Eur. J. Neurosci Volume: 33(4) Pages: 612-621
  • Peer Reviewed
• [Journal Article] 道具的学習と行動制御を研究するモデル実験動物 (2011)
  • Author(s): 小林和人、深堀良二、甲斐信行、岡田佳奈、小林とも子
  • Journal Title: 生体の科学 Volume: Vol.61, No.1 Pages: 47-52
• [Journal Article] Selective Neural Pathway Targeting Reveals Key Roles of Thalamostriatal Projection in the Control of Visual Discrimination (2011)
  • Author(s): Kato, S.; Kuramochi, M.; Kobayashi, K., et al
  • Journal Title: Journal of Neuroscience Volume: 31(47) Issue: 47 Pages: 17169-17179
  • DOI: 10.1523/jneurosci.4005-11.2011
  • Peer Reviewed
• [Journal Article] Sensory input regulates spatial and subtype-specific patterns of neuronal turnover in the adult olfactory bulb (2011)
  • Author(s): Masato Sawada, Naoko Kaneko, Hiroyuki Inada, Hiroaki Wake, Yasuko Kato, Yuchio Yanagawa, Kazuto Kobayashi, Tomomi Nemoto, Junichi Nabekura, Kazunobu Sawamoto
  • Journal Title: Journal of Neuroscience Volume: 31 Issue: 32 Pages: 11587-11596
  • DOI: 10.1523/jneurosci.0614-11.2011
  • Peer Reviewed
• [Journal Article] Postnatal development of tyrosine hydroxylase mRNAexpressing neurons in mouse neostriatum (2011)
  • Author(s): Masuda M, Miura M, Inoue R, Imanishi M, Saino-Saito S, Takada M, Kobayashi K, Aosaki T
  • Journal Title: Eur J Neurosci Volume: 34 Issue: 9 Pages: 1355-1367
  • DOI: 10.1111/j.1460-9568.2011.07873.x
  • Peer Reviewed
• [Journal Article] A lentiviral strategy for highly efficient retrograde gene transfer by pseudotyping with fusion envelope giycoprotein. (2011)
  • Author(s): Kato, S., et al.
  • Journal Title: Hum.Gene Ther. Volume: 22 Pages: 197-206
  • Peer Reviewed
• [Journal Article] Rho/Rho-kinase signaling controls axon patterning of aspecified subpopulation of cranial motor neurons. (2011)
  • Author(s): Kobayashi, K., et al.
  • Journal Title: Eur.J.Neurosci. Volume: 33 Pages: 612-621
  • Peer Reviewed
• [Journal Article] 道具的学習と行動制御を研究するモデル実験動物 (2010)
  • Author(s): 小林和人, ら
  • Journal Title: 生体の科学 Volume: 61 Pages: 47-52
• [Presentation] 分子・細胞標的による脳疾患モデル研究 (2011)
  • Author(s): 小林和人
  • Organizer: 第6回日本統合失調症学会
  • Place of Presentation: 札幌
• [Presentation] Behavioral analysis of the thalamostriatal neural pathway labeled by the retrograde gene transfer. (2010)
  • Author(s): Kato, S., et al.
  • Organizer: 第33回日本神経科学大会、第53回日本神経化学会大会、第20回日本神経回路学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-09-02
• [Presentation] 高頻度逆行性輸送ベクターを利用した視床-線条体路の学習行動における機能の研究 (2010)
  • Author(s): 加藤成樹、小林憲太、深堀良二、小林和人
  • Organizer: 第33回日本神経科学大会、第53回日本神経化学会(神戸)大会、第20回日本神経回路学会大会合同大会
  • Place of Presentation: 神戸
• [Book] Functional circuitry analysis inrodents using neurotoxins/immunotoxins. In Neuromethods, Controlled Genetic Manipulations(ed. Alexei, M.), chapter10 (2012)
  • Author(s): Kobayashi, K., Okada, K., and Kai, N.
  • Publisher: Humana Press Inc.
• [Book] Controlled Genetic Manipulations (2012)
  • Author(s): Kobayashi, K., et al
  • Total Pages: 227
  • Publisher: Neuromethods