Functional analysis of thalamostriatal pathway by lentiviral vector with retrograde axonal transport

• Project/Area Number: 21700354
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neuroscience in general
• Research Institution: Fukushima Medical University
• Principal Investigator: KATO Shigeki 福島県立医科大学, 医学部, 助教 (90443879)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 分子 / 細胞神経科学 / 逆行性レンチウイルスベクター / 視床-線条体神経路 / 特定神経路標識 / 学習 / 記憶 / 逆行性レンチイルスベクター

Research Abstract

A highly efficient retrograde gene transfer lentiviral vector encoding the recombinant immunotoxin(IT) receptor was injected into the dorsolateral striatum in mice to express the receptor in neurons innervating the striatum. IT treatment into the thalamus(PF) of the vector-injected animals caused a selective elimination of neurons of the PF-derived thalamostriatal pathway. The elimination of this pathway impaired the response selection accuracy and delayed the motor response in the acquisition of a visual cue-dependent discrimination task. When the pathway elimination was induced after learning acquisition, it disturbed the response accuracy in the task performance with no apparent change in the response time. These results demonstrate that thalamostriatal projection derived from the PF plays essential roles in the acquisition and execution of discrimination learning in response.

Research Products

• [Journal Article] Dissecting circuit mechanisms by genetic manipulation of specific neural pathways (2012)
  • Author(s): Kato, S., Kobayashi, K., and Kobayashi, K.
  • Journal Title: Rev. Nuerosci. in press Volume: (in press)
  • Peer Reviewed
• [Journal Article] Genetic dissection of the circuit for hand dexterity in primates (2012)
  • Author(s): Kinoshita, M., Matsui, R., Kato, S., Hasegawa, T., Kasahara, H., Isa, K., Watakabe, A., Yamamori, T., Nishimura, Y., Alstermark, B., Watanabe, D., Kobayashi, K., and Isa, T.
  • Journal Title: Nature in press Volume: (in press)
  • Peer Reviewed
• [Journal Article] Immunotoxin-mediated tract targeting in the primate brain : Selective elimination of the cortico-subthalamic "Hyperdirect" pathway (2012)
  • Author(s): Inoue, K., Koketsu, D., Kato, S., Kobayashi, K., Nambu, A., and Takada, M.
  • Journal Title: PLoS ONE Volume: 7 Pages: 39149-39149
  • Peer Reviewed
• [Journal Article] Neuron-specific gene transfer through retrograde transport of lentiviral vector pseudotyped with a novel type of fusion envelope glycoprotein (2011)
  • Author(s): Kato, S., Kuramochi, M., Takasumi, K., Kobayashi, K., Inoue, K., Takahara, D., Hitoshi, S., Ikenaka, K., Shimada, T., Takada, M., and Kobayashi, K.
  • Journal Title: Hum. Gene Ther Volume: 22 Pages: 1511-1523
  • Peer Reviewed
• [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 Pages: 17169-17179
  • Peer Reviewed
• [Journal Article] Dynamic expression of cadherins regulates vocal development in a songbird (2011)
  • Author(s): Matsunaga, E., Suzuki, K., Kato, S., Kurotani, T., Kobayashi, K., and Okanoya, K.
  • Journal Title: PLoS ONE Volume: 6 Pages: 25272-25272
  • 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 Pages: 197-206
  • Peer Reviewed
• [Journal Article] Neuron-specific gene transfer through retrograde transport of lentiviral vector pseudotyped with a novel type of fusion envelope glycoprotein (2011)
  • Author(s): Kato S, Kuramochi M, Takasumi K, Kobayashi K, Inoue K, Takahara D, Hitoshi S, Ikenaka K, Shimada T, Takada M, Kobayashi K
  • Journal Title: Hum Gene Ther Volume: 22 Issue: 12 Pages: 1511-1523
  • DOI: 10.1089/hum.2011.111
  • Peer Reviewed
• [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] Dynamic expression of cadherins regulates vocal development in a songbird (2011)
  • Author(s): Matsunaga, E., et al
  • Journal Title: PLos One Volume: 6 Issue: 9 Pages: e25272-e25272
  • DOI: 10.1371/journal.pone.0025272
  • Peer Reviewed
• [Journal Article] A lentiviral strategy for highly efficient retrograde gene transfer by pseudotyping with fusion envelope glycoprotein. (2011)
  • Author(s): Kato, S., et al.
  • Journal Title: Hum.Gene Ther. Volume: 22 Pages: 197-206
  • Peer Reviewed
• [Journal Article] Reduced sterility with impairment of early-stage embryos observed in mice lacking Lgr4 in epithelial tissues. (2010)
  • Author(s): Mohri, Y., et al.
  • Journal Title: Fertil.Steril. Volume: 94 Pages: 2878-2881
  • Peer Reviewed
• [Presentation] 新規融合糖タンパク質組換え体レンチウイルスベクター系による神経細胞特異的逆行性遺伝子導入 (2011)
  • Author(s): 加藤成樹、倉持真人、高住賢司、小林憲太、井上謙一、高原大輔、等誠司、池中一裕、島田隆、高田昌彦、小林和人
  • Organizer: 第34回日本分子生物学会
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 2011-12-13
• [Presentation] Behavioral role of thalamostriatal neural pathway in conditional discrimination paradigm (2011)
  • Author(s): Shigeki KATO, Masahito KURAMOCHI, Kenta KOBAYASHI, Ryoji FUKABORI, Motokazu UCHIGASHIMA, Masahiko WATANABE, Yuji TSUTSUI and Kazuto KOBAYASHI
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 2011-09-16
• [Presentation] Behavioral role of thalamostriatal neural pathway in conditional discrim ination paradigm (2011)
  • Author(s): 加藤成樹
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 2011-09-16
• [Presentation] 脳神経回路研究のための融合糖タンパク質組換え体レンチウイルスベクター系による高頻度逆行性遺伝子導入 (2010)
  • Author(s): 加藤成樹、小林憲太、井上謙一、倉持真人、岡田知明、八木沼洋行、森本金次郎、島田隆、高田昌彦、小林和人
  • Organizer: 第33回日本分子生物学会
  • Place of Presentation: 神戸・神戸ポートアイランド
  • Year and Date: 2010-12-07
• [Presentation] Analysis of behavioral role of the thalamostriatal neural pathway by using the highly efficient retrograde transport vector. (2010)
  • Author(s): Shigeki KATO, Kenta KOBAYASHI, Ryoji FUKABORI and Kazuto KOBAYASHI
  • Organizer: 第33回日本神経科学大会
  • Place of Presentation: 神戸・神戸ポートアイランド
  • Year and Date: 2010-09-02
• [Presentation] HIGHLY EFFICIENT GENE DELIVERY SYSTEM INTO THE BRAIN THROUGH RETROGRADE AXONAL TRANSPORT BY USING LENTIVIRAL VECTORS PSEUDOTYPED WITH RABIES VIRUS GLYCOPROTEIN AND ITS DERIVATIVES (2010)
  • Author(s): Kazuto Kobayashi, Shigeki Kato, Kenta Kobayashi, Ken-ichi Inoue, Masahiko Takada
  • Organizer: 第16回日本遺伝子治療学会大会
  • Place of Presentation: 宇都宮・宇都宮文化会館
  • Year and Date: 2010-07-02
• [Presentation] HIGHLY EFFICIENT GENE DELIVERY SYSTEM INTO THE BRAIN THROUGH RETROGRADE AXONAL TRANSPORT BY USING LENTIVIRAL VECTORS PSEUDOTYPED WITH RABIES VIRUS GLYCOPROTEIN AND ITS DERIVATIVES. (2010)
  • Author(s): 加藤成樹
  • Organizer: 第16回日本遺伝子治療学会大会
  • Place of Presentation: 宇都宮・宇都宮文化会館
  • Year and Date: 2010-07-02
• [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7回領域内研究報告会
  • Place of Presentation: 大阪・千里ライフサイエンスセンタービル
  • Year and Date: 2010-03-01
• [Presentation] 高頻度逆行性輸送ベクターを利用した視床-線条件路の学習行動における機能の研究 (2010)
  • Author(s): 加藤成樹
  • Organizer: 第7回領域内研究報告会(JST/CREST)
  • Place of Presentation: 大阪・千里ライフサイエンスセンタービル
  • Year and Date: 2010-03-01
• [Presentation] Development of the efficient gene transfer system through a lentiviral vector with retrograde axonal transport for specific neural circuit labeling. (2009)
  • Author(s): Shigeki KATO, Kenta KOBAYASHI, Tomoaki OKADA and Kazuto KOBAYASHI
  • Organizer: 第32回日本分子生物学会
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 2009-12-10
• [Presentation] Immunotoxin targeting of the thalamostriatal neural pathway labeled by the retrograde gene transfer (2009)
  • Author(s): Shigeki KATO, Kenta KOBAYASHI, Tomoaki OKADA and Kazuto KOBAYASHI
  • Organizer: 第33回日本神経科学大会
  • Place of Presentation: 名古屋・名古屋国際会議場
  • Year and Date: 2009-09-17
• [Presentation] Immunotoxin targeting of the thalamostriatal neural pathway labeled by the retrograde gene transfer (2009)
  • Author(s): 加藤成樹
  • Organizer: 第32回日本神経科学大会
  • Place of Presentation: 名古屋・名古屋国際会議場
  • Year and Date: 2009-09-17
• [Book] Viral Gene Therapy(Ke Xu, ed) (2011)
  • Author(s): Kato, S., Kuramochi, M., Kobayashi, K., Inoue, K., Takada, M., and Kobayashi, K.
  • Publisher: In Tech
• [Book] Viral Gene Therapy (2011)
  • Author(s): Kato, S., et al
  • Publisher: Croatia : In Tech