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2019 Fiscal Year Annual Research Report

意欲行動の持続にかかわる神経基盤の解明

Publicly Offered Research

Project AreaCreation and Promotion of the Will-Dynamics
Project/Area Number 19H05027
Research InstitutionKeio University

Principal Investigator

田中 謙二  慶應義塾大学, 医学部(信濃町), 准教授 (30329700)

Project Period (FY) 2019-04-01 – 2021-03-31
Keywords意欲 / 根気 / 腹側海馬 / フォトメトリー
Outline of Annual Research Achievements

海馬CA1活動観察には、海馬CA1神経細胞選択的にyellow cameleon nano50(YC)を発現させたマウス(Htr5b-tTA::tetO-YC)を用いた。海馬CA1に光ファイバーを留置し、行動中の活動観察を行った。
レバーを複数回押すと餌が獲得できる意欲行動(オペラント行動)において、特に、レバーを押している最中には、腹側海馬CA1神経細胞の活動が抑制された。背側海馬CA1神経細胞活動も同様に抑制されるか調べたところ、レバーを押している最中に、背側海馬CA1神経細胞の活動は抑制しなかった。このことから、腹側海馬と背側海馬の機能的な違いが示唆された。
次に、 腹側海馬CA1神経細胞の光操作によって、腹側海馬の活動低下と意欲行動の持続に因果関係があるか調べた。光活性化の実験では、海馬CA1細胞選択的にChR2を発現させたマウス(Htr5b-tTA::tetO-ChR2(C128S))を用いた。腹側海馬の両側に光ファイバーを留置し、レバー押し行動中に限って強制的にCA1神経細胞の活動をを行うと、意欲行動の持続が阻害された。次に、意欲行動中に腹側海馬を光抑制することで、レバー押し行動の持続を促進させるか調べた。腹側海馬の光抑制には、海馬CA1選択的にArchTを発現させたマウス(Htr5b-tTA::tetO-ArchT)を用いた。その結果、CA1神経細胞抑制を更に亢進させると、意欲行動の持続を要求されるタスクにおいて、その成功確率が上がることがわかった。
背側海馬CA1神経細胞に光興奮、光抑制の操作を行ったが、いずれの操作も意欲行動の持続に変化は無かった。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

腹側海馬が意欲行動の持続に関わることを実証できたから。

Strategy for Future Research Activity

腹側海馬CA1神経細胞の活動低下が、どのようなメカニズムを介して行われているのか、特に海馬へ投射するセロトニン神経の役割に注目して調べる。

  • Research Products

    (18 results)

All 2020 2019 Other

All Int'l Joint Research (2 results) Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 3 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] University of Texas, Austin(米国)

    • Country Name
      U.S.A.
    • Counterpart Institution
      University of Texas, Austin
  • [Int'l Joint Research] Uppsala University,(スウェーデン)

    • Country Name
      SWEDEN
    • Counterpart Institution
      Uppsala University,
  • [Journal Article] Identification of Lacrimal Gland Postganglionic Innervation and Its Regulation of Tear Secretion2020

    • Author(s)
      Jin Kai、Imada Toshihiro、Hisamura Ryuji、Ito Masataka、Toriumi Haruki、Tanaka Kenji F.、Nakamura Shigeru、Tsubota Kazuo
    • Journal Title

      The American Journal of Pathology

      Volume: 190 Pages: 1068~1079

    • DOI

      10.1016/j.ajpath.2020.01.007

    • Peer Reviewed
  • [Journal Article] Essential role of microglial transforming growth factor-β1 in antidepressant actions of (R)-ketamine and the novel antidepressant TGF-β12020

    • Author(s)
      Zhang Kai、Yang Chun、Chang Lijia、Sakamoto Akemi、Suzuki Toru、Fujita Yuko、Qu Youge、Wang Siming、Pu Yaoyu、Tan Yunfei、Wang Xingming、Ishima Tamaki、Shirayama Yukihiko、Hatano Masahiko、Tanaka Kenji F.、Hashimoto Kenji
    • Journal Title

      Translational Psychiatry

      Volume: 10 Pages: 32

    • DOI

      10.1038/s41398-020-0733-x

    • Peer Reviewed / Open Access
  • [Journal Article] Correlative study using structural MRI and super-resolution microscopy to detect structural alterations induced by long-term optogenetic stimulation of striatal medium spiny neurons2019

    • Author(s)
      Abe Yoshifumi、Komaki Yuji、Seki Fumiko、Shibata Shinsuke、Okano Hideyuki、Tanaka Kenji F.
    • Journal Title

      Neurochemistry International

      Volume: 125 Pages: 163~174

    • DOI

      10.1016/j.neuint.2019.02.017

    • Peer Reviewed
  • [Journal Article] Serotonin-mediated inhibition of ventral hippocampus is required for sustained goal-directed behavior2019

    • Author(s)
      Yoshida Keitaro、Drew Michael R.、Mimura Masaru、Tanaka Kenji F.
    • Journal Title

      Nature Neuroscience

      Volume: 22 Pages: 770~777

    • DOI

      10.1038/s41593-019-0376-5

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Region- and Cell Type-Specific Facilitation of Synaptic Function at Destination Synapses Induced by Oligodendrocyte Depolarization2019

    • Author(s)
      Yamazaki Yoshihiko、Abe Yoshifumi、Shibata Shinsuke、Shindo Tomoko、Fujii Satoshi、Ikenaka Kazuhiro、Tanaka Kenji F.
    • Journal Title

      The Journal of Neuroscience

      Volume: 39 Pages: 4036~4050

    • DOI

      10.1523/JNEUROSCI.1619-18.2019

    • Peer Reviewed / Open Access
  • [Journal Article] Mechanical regulation of oligodendrocyte morphology and maturation by the mechanosensor p130Cas2019

    • Author(s)
      Shimizu Takeshi、Osanai Yasuyuki、Tanaka Kenji F.、Thai Truc Quynh、Abe Manabu、Natsume Rie、Sakimura Kenji、Ikenaka Kazuhiro
    • Journal Title

      Journal of Neurochemistry

      Volume: 150 Pages: 158~172

    • DOI

      10.1111/jnc.14657

    • Peer Reviewed
  • [Journal Article] App mice overall do not show impaired motivation, but cored amyloid plaques in the striatum are inversely correlated with motivation2019

    • Author(s)
      Hamaguchi Takuya、Tsutsui-Kimura Iku、Mimura Masaru、Saito Takashi、Saido Takaomi C.、Tanaka Kenji F.
    • Journal Title

      Neurochemistry International

      Volume: 129 Pages: 104470~104470

    • DOI

      10.1016/j.neuint.2019.104470

    • Peer Reviewed
  • [Journal Article] Detection of a High-Turnover Serotonin Circuit in the Mouse Brain Using Mass Spectrometry Imaging2019

    • Author(s)
      Sugiyama Eiji、Guerrini Matteo M.、Honda Kurara、Hattori Yuko、Abe Manabu、Kallback Patrik、Andren Per E.、Tanaka Kenji F.、Setou Mitsutoshi、Fagarasan Sidonia、Suematsu Makoto、Sugiura Yuki
    • Journal Title

      iScience

      Volume: 20 Pages: 359~372

    • DOI

      10.1016/j.isci.2019.09.036

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Translational approach to apathy‐like behavior in mice: From the practical point of view2019

    • Author(s)
      Tanaka Kenji F.、Hamaguchi Takuya
    • Journal Title

      Psychiatry and Clinical Neurosciences

      Volume: 73 Pages: 685~689

    • DOI

      10.1111/pcn.12915

    • Peer Reviewed
  • [Journal Article] Neuroprotective effects of microglial P2Y1 receptors against ischemic neuronal injury2019

    • Author(s)
      Fukumoto Yuichiro、Tanaka Kenji F、Parajuli Bijay、Shibata Keisuke、Yoshioka Hideyuki、Kanemaru Kazuya、Gachet Christian、Ikenaka Kazuhiro、Koizumi Schuichi、Kinouchi Hiroyuki
    • Journal Title

      Journal of Cerebral Blood Flow & Metabolism

      Volume: 39 Pages: 2144~2156

    • DOI

      10.1177/0271678X18805317

    • Peer Reviewed
  • [Journal Article] The physiology and pathophysiology of basal ganglia: From signal transduction to circuits2019

    • Author(s)
      Chuhma Nao、Tanaka Kenji F.、Nagai Taku
    • Journal Title

      Neurochemistry International

      Volume: 131 Pages: 104544~104544

    • DOI

      10.1016/j.neuint.2019.104544

    • Int'l Joint Research
  • [Presentation] 意欲行動の神経基盤解明2019

    • Author(s)
      田中謙二
    • Organizer
      第115回日本精神神経学会学術総会
  • [Presentation] Regional blood flow regulation by optogenetics2019

    • Author(s)
      Kenji Tanaka
    • Organizer
      Neuro2019
  • [Presentation] Serotonin-mediated inhibition of ventral hippocampus is required for sustained goal-directed behavior2019

    • Author(s)
      Kenji Tanaka
    • Organizer
      11th Optogenetics meeting
    • Int'l Joint Research / Invited
  • [Presentation] 意欲行動の神経基盤2019

    • Author(s)
      田中謙二
    • Organizer
      大阪大学蛋白質研究所セミナー
    • Invited
  • [Patent(Industrial Property Rights)] 衝動抑制薬のスクリーニング方法、及び衝動抑制薬2019

    • Inventor(s)
      田中謙二
    • Industrial Property Rights Holder
      田中謙二
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      PCT/JP2019/021201
    • Overseas

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Published: 2021-01-27  

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