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プレシナプス分子の動作原理から捉える適応回路メカニズム

Publicly Offered Research

Project AreaMechanisms underlying the functional shift of brain neural circuitry for behavioral adaptation
Project/Area Number 17H05560
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionUniversity of Yamanashi

Principal Investigator

大塚 稔久  山梨大学, 大学院総合研究部, 教授 (40401806)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords神経科学
Outline of Annual Research Achievements

本年度は前年度に引き続き、養育行動後のc-FosとCASTのmRNAの発現をin situハイブリダイゼーションにより脳全体を対象として解析を行った。その結果、養育行動との関連が知られている内側視床前野 (MPOA) の他に室傍視床核 (PVT), 内側乳頭体核 (MMN) などの領域においてc-Fosの発現が増加している様子が見られた。各領域での個々の細胞ごとのc-FosとCASTの発現量の関連性を調べるため、京都大学工学部電気電子工学科の石井信教授から指導していただいた大規模データの解析方法を用いて、PVTにおいてはCASTの発現量も高い傾向があることを見出した。また、養育行動に依存して活性化したPVTの神経細胞においてCASTを特異的にノックアウトする系を構築するため、c-FosプロモーターでCreERT2が発現するAAVベクターを作製した。実際に初代培養神経細胞に感染させると、KCl刺激によりCreERT2の発現が増加し、タモキシフェンにより核内へ移行されることから、発現と核内移行の制御が可能であることが分かった。今後マウスへの感染を行う予定である。さらに、昨年度に作製を始めたCASTおよびELKSのマウスモノクローナル抗体のハイブリドーマの中から、それぞれの特異性を持ちつつ免疫組織染色で使用可能なハイブリドーマのスクリーニングを進め、抗CAST抗体48クローン、抗ELKS抗体25クローンの中から組織染色に用いることができるCAST、ELKSのモノクローナル抗体を得ることに成功した。

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (13 results)

All 2019 2018 2017 Other

All Journal Article (7 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Presentation (5 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] Vangl2 interaction plays a role in the proteasomal degradation of Prickle22019

    • Author(s)
      Nagaoka Tadahiro、Furuse Mikio、Ohtsuka Toshihisa、Tsuchida Kunihiro、Kishi Masashi
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 2912-2912

    • DOI

      10.1038/s41598-019-39642-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ELKS/Voltage-dependent Ca2+ channel-β Subunit Module Regulates Polarized Ca2+ Influx in Pancreatic β-Cells.2019

    • Author(s)
      Ohara-Imaizumi, M., Aoyagi, K., Yamauchi, H., Yoshida, M., Mori, M.X., Hida, Y., Tran, H.N., Ohkura, M., Abe, M., Akimoto, Y., Nakamichi, Y., Nishiwaki, C., Kawakami, H., Hara, K., Sakimura, K., Nagamatsu, S., Mori, Y., Nakai, J., Kakei, M., and Ohtsuka, T.
    • Journal Title

      Cell Reports

      Volume: 26 Issue: 5 Pages: 1213-1226

    • DOI

      10.1016/j.celrep.2018.12.106

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cytomatrix proteins CAST and ELKS regulate retinal photoreceptor development and maintenance2018

    • Author(s)
      Hagiwara Akari、Kitahara Yosuke、Grabner Chad Paul、Vogl Christian、Abe Manabu、Kitta Ryo、Ohta Keisuke、Nakamura Keiichiro、Sakimura Kenji、Moser Tobias、Nishi Akinori、Ohtsuka Toshihisa
    • Journal Title

      The Journal of Cell Biology

      Volume: 217 Issue: 11 Pages: 3993-4006

    • DOI

      10.1083/jcb.201704076

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CAST/ELKS Proteins Control Voltage-Gated Ca2+ Channel Density and Synaptic Release Probability at a Mammalian Central Synapse2018

    • Author(s)
      Dong Wei、Radulovic Tamara、Goral R. Oliver、Thomas Connon、Suarez Montesinos Monica、Guerrero-Given Debbie、Hagiwara Akari、Putzke Travis、Hida Yamato、Abe Manabu、Sakimura Kenji、Kamasawa Naomi、Ohtsuka Toshihisa、Young Samuel M.
    • Journal Title

      Cell Reports

      Volume: 24 Issue: 2 Pages: 284-293.e6

    • DOI

      10.1016/j.celrep.2018.06.024

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mutations in bassoon in individuals with familial and sporadic progressive supranuclear palsy-like syndrome2018

    • Author(s)
      Yabe I, Yaguchi H, Kato Y, Miki Y, Takahashi H, Tanikawa S, Shirai S, Takahashi I, Kimura M, Hama Y, Matsushima M, Fujioka S, Kano T, Watanabe M, Nakagawa S, Kunieda Y, Ikeda Y, Hasegawa M, Nishihara H, Ohtsuka T, Tanaka S, Tsuboi Y, Hatakeyama S, Wakabayashi K, Sasaki H
    • Journal Title

      Sci Rep

      Volume: 8 Issue: 1 Pages: 819-819

    • DOI

      10.1038/s41598-018-19198-0

    • NAID

      120006377499

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synaptic localisation of SRF coactivators, MKL1 and MKL2, and their role in dendritic spine morphology2018

    • Author(s)
      Kaneda Marisa、Sakagami Hiroyuki、Hida Yamato、Ohtsuka Toshihisa、Satou Natsumi、Ishibashi Yuta、Fukuchi Mamoru、Krysiak Anna、Ishikawa Mitsuru、Ihara Daisuke、Kalita Katarzyna、Tabuchi Akiko
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 727-727

    • DOI

      10.1038/s41598-017-18905-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CAST: Its molecular structure and phosphorylation-dependent regulation of presynaptic plasticity2018

    • Author(s)
      Hamada Shun、Ohtsuka Toshihisa
    • Journal Title

      Neurosci. Res.

      Volume: 127 Pages: 25-32

    • DOI

      10.1016/j.neures.2017.12.005

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Molecular structure and function of the presynaptic active zone.2018

    • Author(s)
      Toshihisa Ohtsuka
    • Organizer
      A symposium in honor of Sumiko Mochida-Forefront of Neurotransmitter Release and Calcium Channel Signaling
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Integral system by the active zone proteins CAST and ELKS to control retinal synaptic transmission and photoreceptor remodeling.2018

    • Author(s)
      Ohtsuka T.
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Molecular Mechanisms of Presynaptic Transmission.2018

    • Author(s)
      Ohtsuka T.
    • Organizer
      The first international symposium for frontend brain science: University of Yamanashi 2018.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Integral system by CAST/ELKS protein family to regulate retinal photoreceptor development and maintenance.2018

    • Author(s)
      Ohtsuka T.
    • Organizer
      BRI International Symposium 2018.
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] CAST Phosphorylation in Control of Short-term Plasticity at the presynaptic Active Zones.2017

    • Author(s)
      Ohtsuka T.
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Remarks] 山梨大学医学部生化学講座第一教室ホームページ

    • URL

      http://www.med.yamanashi.ac.jp/basic/bioche01/

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report

URL: 

Published: 2017-04-28   Modified: 2019-12-27  

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