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神経回路ダイナミクスにおける分子機構の解明とその人工的制御

Research Project

Project/Area Number 12J03395
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section国内
Research Field Biomedical engineering/Biological material science
Research InstitutionHokkaido University

Principal Investigator

伊東 大輔  北海道大学, 先端生命科学研究院, 特別研究員(PD)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywords培養神経回路網 / 多電極アレイ / 同期バースト / 長期培養 / 遺伝子発現解析 / 神経活動依存的遺伝子発現 / 最初期遺伝子
Outline of Annual Research Achievements

本研究の目的は、培養神経回路網で生じるダイナミクスに寄与する分子を明らかにすることである。ラット胎児大脳皮質由来神経細胞を1ヶ月超に渡って長期培養し、多電極システムを用いて培養神経回路網で生じるスパイクを計測・解析した結果、培養7日目ほどで生じ始めたランダムなスパイク列は、培養14日目ほどにはバースト状のスパイクが複数のニューロンで同期する同期バーストへと移行し、この同期バーストは培養1ヶ月超に渡って維持されることが明らかとなった。この回路ダイナミクスを引き起こす分子を明らかにするために、逆転写PCR法を用い、培養神経回路網の長期発達過程における遺伝子発現解析を行ったところ、Arc、c-fos、egr1等の最初期遺伝子群が培養2週目以降に発現する傾向が確認できた。そこで遺伝子発現を定量的に調べるために、リアルタイムPCRを用いて定量解析を行った。その結果、転写因子であるCreb1遺伝子は、培養28日間に渡ってほぼ一定の発現量が見られた。一方、最初期遺伝子の一つであるArcの発現は培養10日目に約2倍に上昇し、14日目には約12倍まで上昇した。その後発現量は緩やかに下降し、28日目には1日目の基準まで減少した。同様に最初期遺伝子の一つであるc-fosの発現は、培養14日目から上昇し始め、その後徐々に上昇し、28日目には約6倍となった。このように、転写因子であるCreb1が常に一定量発現しているのに対し、最初期遺伝子であるArcおよびc-fosは培養10日目、14日目から発現が上昇するという違いが見られた。同じ最初期遺伝子でも、Arcとc-fosの発現上昇については異なった挙動が見られたのは興味深い。これら最初期遺伝子の発現上昇時期と同期バーストが生じる時期がほぼ一致しており、同期バーストの発生には転写因子の活性化による最初期遺伝子の発現が関係していることが示唆された。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (29 results)

All 2014 2013 2012

All Journal Article (9 results) (of which Peer Reviewed: 8 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (20 results) (of which Invited: 3 results)

  • [Journal Article] Developmental Process and Synchronized Bursts in Cultured Neuronal Networks2014

    • Author(s)
      伊東大輔、郷原一寿
    • Journal Title

      Seibutsu Butsuri

      Volume: 54 Issue: 4 Pages: 210-214

    • DOI

      10.2142/biophys.54.210

    • NAID

      130004677776

    • ISSN
      0582-4052, 1347-4219
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Analysis of related molecules to synchronized burst activity of rat cultured cortical networks2014

    • Author(s)
      D. Ito, K. Gohara
    • Journal Title

      Proc. MEA Meeting 2014

      Volume: 9 Pages: 143-146

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spontaneous and evoked activity in patterned multi-cluster neuronal networks2014

    • Author(s)
      M. Anisimova, K. Yokoyama, D. Ito, M. Suzuki, T. Uchida, K. Gohara
    • Journal Title

      Proc. MEA Meeting 2014

      Volume: 9 Pages: 170-171

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Measurment of saturation processes in glutamatergic and GABAergic synapse densities during long-term development of cultured rat cortical networks2013

    • Author(s)
      D. Ito, T. Komatsu, K. Gohara
    • Journal Title

      Brain Research

      Volume: 1,534 Pages: 22-32

    • DOI

      10.1016/j.brainres.2013.08.004

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis and control of cultured neuronal networks using multi-electrode arrays : from gene expression to network dynamics2013

    • Author(s)
      D. Ito, K. Yokoyama, T. Uchida, K. Gohara
    • Journal Title

      Proceedings of Topical Problems of Biophotonics 2013

      Pages: 231-232

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Neuronal cell pattering on a multi-electrode array for a network analysis platform2013

    • Author(s)
      M. Suzuki, K. Ikeda, M. Yamaguchi, S. Kudoh, K. Yokoyama, R. Satoh, D. Ito, M. Nagayama, T. Uchida, K. Gohara
    • Journal Title

      Biomaterials

      Volume: 34(21) Issue: 21 Pages: 5210-5217

    • DOI

      10.1016/j.biomaterials.2013.03.042

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of gene expression underlying network activity during long-term development of rat cortical cultured neurons2012

    • Author(s)
      D. Ito, K. Yokoyama, K. Gohara
    • Journal Title

      Proceedings of MEA Meeting 2012

      Pages: 65-66

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Return map analysis of synchronized bursts in cultured neuronal networks2012

    • Author(s)
      K. Yokoyama, D. Ito, K. Gohara
    • Journal Title

      Proceedings of MEA Meeting 2012

      Pages: 80-81

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Xenon-induced inhibition of synchronized bursts in a rat cortical neuronal network2012

    • Author(s)
      T. Uchida, S. Suzuki, Y. Hirano, D. I to, M. Nagayama, K. Gohara
    • Journal Title

      Neuroscience

      Volume: 214 Pages: 149-158

    • DOI

      10.1016/j.neuroscience.2012.03.063

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 培養神経回路網における同期バースト活動に関わる分子の探索2014

    • Author(s)
      伊東大輔
    • Organizer
      第52回日本生物物理学会年会
    • Place of Presentation
      札幌コンベンションセンター(北海道)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] ラット培養神経回路網の同期バースト活動に関わる分子の探索2014

    • Author(s)
      伊東大輔
    • Organizer
      平成26年 電気学会 電子・情報・システム部門大会
    • Place of Presentation
      島根大学松江キャンパス(松江市)
    • Year and Date
      2014-09-03 – 2014-09-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of related molecules to synchronized bursts of rat cultured neuronal networks2014

    • Author(s)
      D. Ito
    • Organizer
      9th FENS Forum of Neuroscience
    • Place of Presentation
      Milano Congressi (Italy)
    • Year and Date
      2014-07-05 – 2014-07-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of spontaneous and evoked signal propagation in patterned neuronal networks on multi-electrode arrays2014

    • Author(s)
      M. Anisimova
    • Organizer
      9th FENS Forum of Neuroscience
    • Place of Presentation
      Milano Congressi (Italy)
    • Year and Date
      2014-07-05 – 2014-07-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Spontaneous and evoked activity in patterned multi-cluster neuronal networks2014

    • Author(s)
      M. Anisimova
    • Organizer
      9th International Meeting on Substrate-Integrated Microelectrode Arrays
    • Place of Presentation
      Stadthalle in Reutlingen (Germany)
    • Year and Date
      2014-07-01 – 2014-07-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of related molecules to synchronized burst activity of rat cultured cortical networks2014

    • Author(s)
      D. Ito
    • Organizer
      9th International Meeting on Substrate-Integrated Microelectrode Arrays
    • Place of Presentation
      Stadthalle in Reutlingen (Germany)
    • Year and Date
      2014-07-01 – 2014-07-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis of sygnal propagation in the isolated patterned cortical neuronal networks2014

    • Author(s)
      Margarita Anisimova, 横山慶子、伊東大輔、鈴木正昭、内田努、郷原一寿
    • Organizer
      平成25年度日本生物物理学会北海道支部例会
    • Place of Presentation
      北海道大学(札幌市)
    • Year and Date
      2014-03-11
    • Related Report
      2013 Annual Research Report
  • [Presentation] ラット大脳皮質ニューラルネットワークにおける同期バースト活動のキセノンガスによる抑制効果2014

    • Author(s)
      田邊隆太郎、窪田竜也、伊東大輔、郷原一寿、内田努
    • Organizer
      平成25年度北大細胞生物研究集会
    • Place of Presentation
      北海道大学(札幌市)
    • Year and Date
      2014-03-10
    • Related Report
      2013 Annual Research Report
  • [Presentation] Analysis of related molecules to synchronous activity of rat cultured neuronal networks during long-term development2014

    • Author(s)
      D. Ito, K. Gohara
    • Organizer
      International Life-Science Syposium for Young Scientists
    • Place of Presentation
      北海道大学(札幌市)
    • Year and Date
      2014-03-06
    • Related Report
      2013 Annual Research Report
  • [Presentation] Analysis of electrical activity in a single neuron2013

    • Author(s)
      K. Yokoyama, I. Suzuki, D. Ito, K. Gohara
    • Organizer
      Neuroscience 2013
    • Place of Presentation
      San Diego Convention Center (USA)
    • Year and Date
      2013-11-12
    • Related Report
      2013 Annual Research Report
  • [Presentation] Analysis of moleculer mechanismss underlying synchronized bursts during long-term development of rat cultured neuronal networks2013

    • Author(s)
      D. Ito, K. Yokoyama, K. Gohara
    • Organizer
      Neuroscience 2013
    • Place of Presentation
      San Diego Convention Center (USA)
    • Year and Date
      2013-11-10
    • Related Report
      2013 Annual Research Report
  • [Presentation] Analysis of related molecules to synchronized activity of rat cultured neuronal networks2013

    • Author(s)
      D. Ito, K. Yokoyama, K. Gohara
    • Organizer
      第51回日本生物物理学会年会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      2013-10-28
    • Related Report
      2013 Annual Research Report
  • [Presentation] Analysis and control of cultured neuronal networks using multi-electrodearrays : from gene expression to network dynamics2013

    • Author(s)
      D. Ito, K. Yokoyama, T. Uchida, K. Gohara
    • Organizer
      Topical Problemes of Biophotonics-2013
    • Place of Presentation
      Georgy Zhukov (Russia)
    • Year and Date
      2013-07-22
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 培養神経回路網の長期スパイク計測とイメージング解析2013

    • Author(s)
      伊東大輔
    • Organizer
      イメージングブートキャンプ2013
    • Place of Presentation
      北海道大学(札幌市)
    • Year and Date
      2013-06-11
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 培養神経回路網における同期現象を司る分子の探索2013

    • Author(s)
      伊東大輔
    • Organizer
      2012年度日本生物物理学会北海道支部例会
    • Place of Presentation
      北海道大学(札幌市)
    • Year and Date
      2013-03-05
    • Related Report
      2012 Annual Research Report
  • [Presentation] Analysis of functional molecules underlying, synchronized bursts during long-term development of rat cultured neuronal networks2012

    • Author(s)
      D. I to
    • Organizer
      Neuroscience 2012
    • Place of Presentation
      Ernest N. Morial Convention Center (USA)
    • Year and Date
      2012-10-14
    • Related Report
      2012 Annual Research Report
  • [Presentation] Analysis of functional molecules underlying synchronous activity during long-term development of rat cultured neuronal networks2012

    • Author(s)
      伊東大輔
    • Organizer
      日本生物物理学会第50回年会
    • Place of Presentation
      名古屋大学(名古屋市)
    • Year and Date
      2012-09-22
    • Related Report
      2012 Annual Research Report
  • [Presentation] Analysis of functional molecules underlying synchronized bursts during long-term development of cultured rat neuronal networks2012

    • Author(s)
      伊東大輔
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋国際会議場(愛知県)
    • Year and Date
      2012-09-21
    • Related Report
      2012 Annual Research Report
  • [Presentation] Analysis of gene expression underlying synchronized bursts in a rat cortical cultured networks2012

    • Author(s)
      D. Ito
    • Organizer
      8th FENS Forum of Neuroscience
    • Place of Presentation
      Barcelona International Convention Center (Spain)
    • Year and Date
      2012-07-17
    • Related Report
      2012 Annual Research Report
  • [Presentation] Analysis of gene expression underlying network activity during long-term development of rat cortical cultured neurons2012

    • Author(s)
      D. I to
    • Organizer
      8th International Meeting on Substrate-Integrated Microelectrode Arrays
    • Place of Presentation
      Friedrich-List-Halle(Germany)
    • Year and Date
      2012-07-12
    • Related Report
      2012 Annual Research Report

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Published: 2013-04-25   Modified: 2024-03-26  

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