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Development of animal model enabling the manipulation of intracellular Ca level

Research Project

Project/Area Number 24650219
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Fusional basic brain science
Research InstitutionKeio University

Principal Investigator

TANAKA Kenji  慶應義塾大学, 医学部, 特任准教授 (30329700)

Co-Investigator(Kenkyū-buntansha) MATSUI Ko  生理学研究所, 大学共同利用機関等の部局, 准教授 (20435530)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords遺伝子改変マウス / tet system / メラノプシン / チャネルロドプシン / カルシウム / 生理学 / バイオテクノロジー / 応用動物 / オプトジェネティクス
Research Abstract

To achieve the manipulation of intracellular Ca2+ levels in the cell-type specific manner, we established the transgenic animal in which melanopsin (human OPN4 gene) was expressed in cell-type specific manner. We generated tetO-melanopsin transgenic mice and crossed with neuronal tTA (orexin-tTA) mice. Orexin neurons expressed enough amount of melanopsin to evoke cell firing, demonstrating the successful manipulation. In case of crossing with glial tTA mice, there was no induction. To improve melanopsin induction in glial cells, we generated STOP tetO-melanopsin knockin mice using mouse melanopsin locus. Unlike previous tetO knockin mice, none of glial tTA line induced melanopsin yet. We were able to express sufficient amount of melanopsin in neuronal cells and manipulate cell function by illumination, however, we failed to express melanopsin in glial cells.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (45 results)

All 2014 2013 2012 2011 Other

All Journal Article (18 results) (of which Peer Reviewed: 15 results) Presentation (25 results) (of which Invited: 9 results) Remarks (2 results)

  • [Journal Article] Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage2014

    • Author(s)
      Beppu K, Sasaki T, Tanaka K F, Yamanaka A, Fukazawa Y, Shigemoto R, Matsui K
    • Journal Title

      Neuron

      Volume: 81(2) Issue: 2 Pages: 314-320

    • DOI

      10.1016/j.neuron.2013.11.011

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 光遺伝学に有用な遺伝子改変マウス オプトジェネティクスを用いた神経機能操作の現在地~光で行動をコントロールする~2014

    • Author(s)
      田中 謙二
    • Journal Title

      細胞工学

      Volume: 33 Pages: 260-263

    • Related Report
      2013 Annual Research Report
  • [Journal Article] The manipulation of neural and cellular activities by ectopic expression of melanopsin.2013

    • Author(s)
      Koizumi A, Tanaka KF, Yamanaka A
    • Journal Title

      Neuroscience Research

      Volume: 75(1) Issue: 1 Pages: 3-5

    • DOI

      10.1016/j.neures.2012.07.010

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ectopic expression of melanopsin in orexin/hypocretin neurons enables control of wakefulness of mice in vivo by blue light2013

    • Author(s)
      Tsunematsu T, Tanaka KF, Yamanaka A, Koizumi A
    • Journal Title

      Neurosci Res

      Volume: 75(1) Issue: 1 Pages: 23-28

    • DOI

      10.1016/j.neures.2012.07.005

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Influence of inhibitory serotonergic inputs to orexin/hypocretin neurons on the diurnal rhythm of sleep and wakefulness.2013

    • Author(s)
      Tabuchi S, Tsunematsu T, Kilduff TS, Sugio S, Tanaka KF, Takahashi S, Tominaga M, Yamanaka A
    • Journal Title

      Sleep

      Volume: 36(9) Issue: 9 Pages: 1391-1404

    • DOI

      10.5665/sleep.2972

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-lasting silencing of orexin/hypocretin neurons using archaerhodopsin induces slow-wave sleep in mice.2013

    • Author(s)
      Tsunematsu T, Tabuchi S, Tanaka KF, Boyden ES, Tominaga M, Yamanaka A
    • Journal Title

      Behavioural Brain Research

      Volume: 255 Pages: 64-74

    • DOI

      10.1016/j.bbr.2013.05.021

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vivoでグリアを見る・操作するための機能遺伝子発現方法2013

    • Author(s)
      田中 謙二、高田 則雄、三村 將
    • Journal Title

      実験医学

      Volume: 31 Pages: 1736-1741

    • Related Report
      2013 Annual Research Report
  • [Journal Article] オプトジェネティクスと精神医学.2013

    • Author(s)
      田中 謙二、高田 則雄、三村 將
    • Journal Title

      精神神経学雑誌

      Volume: 115 Pages: 1211-1215

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Olig2-lineage cells preferentially differentiate into oligodendrocytes but their processes degenerate at the chronic demyelinating stage of proteolipid protein-overexpressing mouse.2013

    • Author(s)
      Shimizu T
    • Journal Title

      J Neurosci Res

      Volume: 91 Issue: 2 Pages: 178-186

    • DOI

      10.1002/jnr.23153

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Application of an optogenetic byway for perturbing neuronal activity via glialphotostimulation.2012

    • Author(s)
      T. Sasaki. K. Beppu, K. Tanaka, Y. Fukazawa, R. Shigemoto, K. Matsui
    • Journal Title

      Proceedings National Academy of Sciences of the USA

      Volume: 109 Issue: 50 Pages: 20720-20725

    • DOI

      10.1073/pnas.1213458109

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Expanding the repertoire of optogenetically targeted cells with an enhanced gene expression system2012

    • Author(s)
      K. Tanaka, K. Matsui, T. Sasaki. H. Sano, S. Sugio, K. Fan, K. Ikenaka, R. Hen, J. Nakai, Y. Yanagawa, H. Hasuwa, K. Deisseroth, A. Yamanaka
    • Journal Title

      Cell Reports

      Volume: 2 Issue: 2 Pages: 397-406

    • DOI

      10.1016/j.celrep.2012.06.011

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Preinspiratory calcium rise in putative pre-Botzinger complex astrocytes2012

    • Author(s)
      Y. Okada, T. Sasaki. Y. Oku, N. Takahashi, M. Seki, S. Ujita, K. Tanaka, N. Matsuki, Y. Ikegaya
    • Journal Title

      Journal of Physiology

      Volume: 590 Issue: 19 Pages: 4933-4944

    • DOI

      10.1113/jphysiol.2012.231464

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of optogenetically activated striatal medium spiny neurons by Npas4 expression2012

    • Author(s)
      Bepari AK, Sano H, Tamamaki N, Nambu A, Tanaka KF, Takebayashi H
    • Journal Title

      PLoS ONE

      Volume: 7(12) Issue: 12 Pages: 140-140

    • DOI

      10.1371/journal.pone.0052783

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Shared Synaptic Pathophysiology in Syndromic and Nonsyndromic Rodent Models of Autism2012

    • Author(s)
      Baudouin SJ
    • Journal Title

      Science

      Volume: 338 Issue: 6103 Pages: 128-132

    • DOI

      10.1126/science.1224159

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serotonin receptor expression along the dorsal-ventral axis of mouse hippocampus.2012

    • Author(s)
      Tanaka KF
    • Journal Title

      Philos Trans R Soc Lond B Biol

      Volume: 367 Issue: 1601 Pages: 2395-2401

    • DOI

      10.1098/rstb.2012.0038

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mitral cells in the olfactory bulb are mainly excited through a multistep signaling path.2012

    • Author(s)
      Gire DH
    • Journal Title

      J Neurosci.

      Volume: 32 Issue: 9 Pages: 2964-2975

    • DOI

      10.1523/jneurosci.5580-11.2012

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased astrocytic ATP release results in enhanced excitability of the hippocampus.2012

    • Author(s)
      Lee HU, Yamazaki Y, Tanaka KF, Furuya K, Sokabe M, Hida H, Takao K, Miyakawa T, Fujii S, Ikenaka K.
    • Journal Title

      These^† authors contributed equally to this work

      Volume: 61 Issue: 2 Pages: 210-224

    • DOI

      10.1002/glia.22427

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gene induction in mature oligodendrocytes with a PLP-tTA mouse line2011

    • Author(s)
      Inamura N, et al
    • Journal Title

      Genesis

      Volume: (online published) Issue: 5 Pages: 424-428

    • DOI

      10.1002/dvg.20808

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] cortical spreading depressionがどこで止まるか2014

    • Author(s)
      吉田 慶多朗、田中 謙二
    • Organizer
      第19回グリアクラブ
    • Place of Presentation
      新潟
    • Related Report
      2013 Annual Research Report
  • [Presentation] オプトジェネティクス2014

    • Author(s)
      田中 謙二
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] てんかん原性域の局所温度上昇とTPRV4wo介した病態悪化2014

    • Author(s)
      柴崎 貢志、田中 謙二、石崎 泰樹
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島
    • Related Report
      2013 Annual Research Report
  • [Presentation] オプトジェネティクスとfMRIを融合させたグリアニューロン相互作用の解析2014

    • Author(s)
      田中謙二、吉田慶多朗、徐明、疋島啓吾、岡野栄之、三村將、高田則雄
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] In vivo Ca2+ imaging of vascular smooth muscle cells in cerebral cortex2014

    • Author(s)
      Nami Kitajima, Hiroshi Sekiya, Kazunori Kanemaru, Kenji F. Tanaka, Masamitsu Iino
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台
    • Related Report
      2013 Annual Research Report
  • [Presentation] グリア細胞の光操作2013

    • Author(s)
      田中謙二
    • Organizer
      第24回マイクロダイアリシス研究会
    • Place of Presentation
      東京
    • Year and Date
      2013-12-14
    • Related Report
      2013 Final Research Report
  • [Presentation] グリアが起点となる脳内環境変化2013

    • Author(s)
      田中謙二
    • Organizer
      Neuro2013
    • Place of Presentation
      京都
    • Year and Date
      2013-06-20
    • Related Report
      2013 Final Research Report
  • [Presentation] Expanding the repertoire of optogenetically targeted cells with an enhanced gene expression system2013

    • Author(s)
      Kenji Tanaka
    • Organizer
      OPTOGENETICS-2013 Theme Conference
    • Place of Presentation
      Boston, USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Expanding the repertoire of optogenetically targeted cells with an enhanced gene expression system.2013

    • Author(s)
      Kenji Tanaka
    • Organizer
      Optogenetics-2013 Thema Conference
    • Place of Presentation
      Boston
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] オプトジェネティクスと精神医学2013

    • Author(s)
      田中 謙二
    • Organizer
      第109回 日本精神神経学会学術総会
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 一度創って5度おいしいマウス2013

    • Author(s)
      田中 謙二、高田 則雄
    • Organizer
      包括脳ネットワーク夏のワークショップ
    • Place of Presentation
      名古屋
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Npas4 mRNA expression can trace photoactivation of striatal medium spiny neurons at the cellular level.2013

    • Author(s)
      竹林 浩秀
    • Organizer
      第118回日本解剖学会総会・全国学術集会
    • Place of Presentation
      香川
    • Related Report
      2012 Research-status Report
  • [Presentation] 光遺伝学を用いたチャネルロドプシン発現アストロサイトの活性化は神経活動を亢進させる2013

    • Author(s)
      吉田 慶多朗
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京 江戸川区
    • Related Report
      2012 Research-status Report
  • [Presentation] 精神科領域に重要な投射神経の発火をコントロールするマウスの開発2013

    • Author(s)
      田中 謙二
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京 江戸川区
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 光操作による細胞機能制御2012

    • Author(s)
      田中 謙二
    • Organizer
      光操作研究会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] 発達期プルキンエ細胞体における登上線維シナプス排除機構2012

    • Author(s)
      宮崎 太輔
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] ChR2-induced astrocytic depolarization augments neuronal activities in vivo.2012

    • Author(s)
      高田 則雄
    • Organizer
      APRU-BMAP 2012/FIRST 2012シンポジウム「脳/心の進化と疾患(Diseases and Evolution of Brain and Mind)」
    • Place of Presentation
      東京 港区
    • Related Report
      2012 Research-status Report
  • [Presentation] グリアが起点となる脳内環境変化

    • Author(s)
      田中 謙二
    • Organizer
      Neuro2013
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] ごきげんの解明に必要な技術:オプトジェネティクス

    • Author(s)
      田中 謙二、高田 則雄
    • Organizer
      The 8th HOKKAIDO ANTI AGING CLUB2014
    • Place of Presentation
      北海道虻田郡
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 疾患モデルマウス作成に有効なSTOPtetO ノックイン(FAST システム)とその応用例

    • Author(s)
      田中謙二
    • Organizer
      難治疾患共同研究拠点シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] グリア細胞の光操作

    • Author(s)
      田中 謙二、吉田 慶多朗、Ming Xu
    • Organizer
      第24回マイクロダイアリシス研究会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] オプトジェネティクスの精神科学への応用

    • Author(s)
      田中 謙二
    • Organizer
      第16回 神経科学領域における分子モニタリングシンポジウム
    • Place of Presentation
      名古屋
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 大脳皮質における血管平滑筋Ca2+イメージング

    • Author(s)
      北島 奈美、関谷 敬、金丸 和典、田中 謙二、飯野 正光
    • Organizer
      筋生理の集い
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] 蛍光Caプローブを発現するトランスジェニックマウスを用いた脳血流制御機構の可視化解析

    • Author(s)
      関谷敬、北島奈美、佐藤要、田中謙二、飯野正光
    • Organizer
      第23回日本循環薬理学会
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] グリアの光操作

    • Author(s)
      田中 謙二
    • Organizer
      第2回 Neurovascular Unit研究会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://keioect.web.fc2.com/keioect/Top_Page.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 生理学研究所 生きたままのマウスの脳細胞を光で操作する技術の開発

    • URL

      http://www.nips.ac.jp/contents/release/entry/2012/07/post-219.html

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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