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Elucidating mechanisms of synapse specificity in the mouse olfactory system

Research Project

Project/Area Number 16H06144
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Nerve anatomy/Neuropathology
Research InstitutionThe University of Tokyo

Principal Investigator

Takeuchi Haruki  東京大学, 大学院薬学系研究科(薬学部), 特任准教授 (70548859)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥24,700,000 (Direct Cost: ¥19,000,000、Indirect Cost: ¥5,700,000)
Fiscal Year 2018: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2017: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2016: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Keywords神経回路形成 / 神経科学 / 嗅覚 / 発生 / 分子生物学 / 神経活動 / カルシウムイメージング / 神経発生 / 自発活動 / 電気生理学 / 嗅覚受容体 / 神経回路 / シナプス / 回路形成 / シナプス特異性 / 発生学 / 脳・神経
Outline of Final Research Achievements

Neural circuits emerge through the interplay of genetic programming and activity-dependent process. During the development of mouse olfactory map, axons segregate into distinct glomeruli in an olfactory receptor (OR)-dependent manner. ORs generate a combinatorial code of axon-sorting molecules, whose expression is regulated by neural activity. However, how neural activity induces OR-specific expression patterns of axon-sorting molecules remains unclear. Here we revealed that the temporal patterns of spontaneous neuronal spikes were not spatially-organized, but were correlated with the OR types. Moreover, optogenetically differentiated patterns of neuronal activity induced specific expression of the corresponding axon-sorting molecules and regulated axonal segregation. Thus, OR-dependent temporal patterns of spontaneous activity play instructive roles in generating the combinatorial code of axon-sorting molecules during olfactory map formation.

Academic Significance and Societal Importance of the Research Achievements

ヒトを含む高等動物の脳は、複雑かつ精緻な神経回路を用いて感覚入力情報に対して適切な出力行動を行う。この情報処理を担う神経回路の破綻は、精神・神経疾患の原因であることから、神経回路形成のメカニズムを解明することは基礎科学のみならず臨床の分野において重要な示唆を与えうる。
一般に高等動物の神経回路は、遺伝的プログラムに加えて臨界期に生じる神経活動に依存した回路の精緻化を経て完成される。この活動に依存した回路の可塑的な変化は、神経細胞間の同期的な発火活動による(ヘブ則)と多くの教科書に記載されている。しかし今回我々は、既存のヘブ則に当てはまらない新規の活動依存的な回路構築のメカニズムを明らかにした。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (37 results)

All 2019 2018 2017 2016

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (31 results) (of which Int'l Joint Research: 16 results,  Invited: 2 results)

  • [Journal Article] Sharp wave-associated activity patterns of olfactory cortical neurons in the mouse piriform cortex2018

    • Author(s)
      Katori K, Manabe H, Nahashima A, Eerdunfu, Ikegaya Y, and Takeuchi H
    • Journal Title

      European Journal of Neuroscience

      Volume: 48 Issue: 10 Pages: 3246-3254

    • DOI

      10.1111/ejn.14099

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Possible requirement of executive functions for high performance in soccer2018

    • Author(s)
      Sakamoto S, Takeuchi H, Ihara N, Ligao B, Suzukawa K
    • Journal Title

      PLOS one

      Volume: 13 Issue: 8 Pages: e0201871-e0201871

    • DOI

      10.1371/journal.pone.0201871

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quadruple Immunostaining of the Olfactory Bulb for Visualization of Olfactory Sensory Axon Molecular Identity Codes2017

    • Author(s)
      Ihara Naoki、Ikegaya Yuji、Takeuchi Haruki
    • Journal Title

      Journal of visualized experiments

      Volume: 00 Issue: 124 Pages: 99-100

    • DOI

      10.3791/55893

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nrp2 is sufficient to instruct circuit formation of mitral-cells to mediate odour-induced attractive social responses2017

    • Author(s)
      K. Inokuchi, F. Imamura, H. Takeuchi, R. Kim, H. Okuno, H. Nishizumi, H. Bito, T. Kikusui, H. Sakano
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 15977-15977

    • DOI

      10.1038/ncomms15977

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differential timing of neurogenesis underlies dorsal-ventral topographic projection of olfactory sensory neurons2017

    • Author(s)
      Eerdunfu、Ihara Naoki、Ligao Bao、Ikegaya Yuji、Takeuchi Haruki
    • Journal Title

      Neural Development

      Volume: 12 Issue: 1

    • DOI

      10.1186/s13064-017-0079-0

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differential expression of axon-sorting molecules in mouse olfactory sensory neurons2016

    • Author(s)
      Ihara Naoki、Nakashima Ai、Hoshina Naosuke、Ikegaya Yuji、Takeuchi Haruki
    • Journal Title

      European Journal of Neuroscience

      Volume: 44 Issue: 3 Pages: 1998-2003

    • DOI

      10.1111/ejn.13282

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 梨状皮質における睡眠時鋭波中の規則的な神経活動2019

    • Author(s)
      香取和生、池谷裕二、竹内春樹
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] テルビウムドープガラスの蛍光を手がかりにした標的パッチクランプ法2019

    • Author(s)
      岡本和樹、藤井直樹、蛯名鉄平、小西邦昭、佐藤由宇、中野利沙子、日置寛之、山口瞬、竹内春樹、湯本潤司、松崎政紀、池谷裕二
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 神経細胞における可逆的タンパク質高速分解システムの構築2019

    • Author(s)
      中野利沙子、森川勝太、伊原尚樹、安藤めぐみ、鐘巻将人、小山隆太、竹内春樹、池谷裕二
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Structured spike series specify gene expression patterns for olfactory circuit formation2019

    • Author(s)
      中嶋藍、伊原尚樹、池谷裕二、竹内春樹
    • Organizer
      第22回日韓薬理合同セミナー
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 嗅覚梨状皮質における大規模単一細胞解析2019

    • Author(s)
      竹内春樹
    • Organizer
      The 6th Chemosensation and Behavior Workshop
    • Related Report
      2018 Annual Research Report
  • [Presentation] 梨状皮質における睡眠時の神経活動2019

    • Author(s)
      香取和生、竹内春樹
    • Organizer
      The 6th Chemosensation and Behavior Workshop
    • Related Report
      2018 Annual Research Report
  • [Presentation] A non-Hebbian activity-dependent mechanism underlying olfactory circuit formation2018

    • Author(s)
      竹内春樹、中嶋藍、伊原尚樹、池谷裕二
    • Organizer
      日本味と匂学会第52回大会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マウス嗅覚系の神経回路の堅牢性に関わる軸索選別分子の発現2018

    • Author(s)
      山下龍馬、中嶋藍、野仲航司、伊原尚樹、井ノ口霞、エルドンフ、池谷裕二、竹内春樹
    • Organizer
      第139回日本薬理学会関東部会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 嗅覚皮質における睡眠時の規則的な神経活動2018

    • Author(s)
      香取和生、眞部寛之、中嶋藍、エルドンフ、佐々木拓哉、池谷裕二、竹内春樹
    • Organizer
      東京大学こころの多様性と適応の統合的研究機構シンポジウム「こころの適応を探る」
    • Related Report
      2018 Annual Research Report
  • [Presentation] Patterned, but not synchronous spontaneous activity of developing olfactory neurons regulates olfactory receptor-specific axon sorting2018

    • Author(s)
      Takeuchi H, Nakashima A, Ihara N and Ikegaya Y
    • Organizer
      Cold Spring Harbor Laboratory Meeting: Molecular Mechanisms of Neuronal Connectivity
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sequential activities of cortical neurons in the mouse piriform cortex during sharp wave2018

    • Author(s)
      Katori, K., Manabe, H., Nakashima, A., Sasaki, T., Ikegaya, Y., Takeuchi H
    • Organizer
      Cold Spring Harbor Asia Conference
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Patterned, but not synchronous spontaneous activity of developing olfactory neurons regulates olfactory receptor-specific axon sorting2018

    • Author(s)
      Takeuchi H, Nakashima A, Ihara N and Ikegaya Y
    • Organizer
      Gordon Research Conference: Molecular and Cellular Neurobiology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A Combinatorial expression of axon-sorting molecules ensures robustness to neural activity changes for neural map formation in the mouse olfactory system2018

    • Author(s)
      Ihara N, Nakashima A, Nonaka K, Ihara N, Ikegaya Y, and Takeuchi H
    • Organizer
      Gordon Gordon Research Conference: Molecular and Cellular Neurobiology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Patterned, but not synchronous spontaneous activity of developing olfactory neurons regulates olfactory receptor-specific axon sorting2018

    • Author(s)
      Nakashima A, Ihara N, Ikegaya Y, Takeuchi H
    • Organizer
      22nd Biennial Meeting of the International Society of Developmental Neuroscience
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Patterned, but not synchronous spontaneous activity of developing olfactory neurons regulates olfactory receptor-specific axon sorting2018

    • Author(s)
      Takeuchi Haruki, Nakashima Ai, Ihara Naoki, and Ikegaya Yuji
    • Organizer
      Keystone Symposia A2: State of the Brain: Genetic Dissection of Brain Circuits and Behavior in Health and Disease
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sharp wave-associated activity patterns of olfactory cortical neurons in the mouse piriform cortex2018

    • Author(s)
      Katori Kazuki, Manabe Hiroyuki, Ikegaya Yuji and Takeuchi Haruki
    • Organizer
      Keystone Symposia A2: State of the Brain: Genetic Dissection of Brain Circuits and Behavior in Health and Disease
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 梨状皮質の神経活動パターン解析2018

    • Author(s)
      竹内春樹
    • Organizer
      The 5th Chemosensation and Behavior Workshop
    • Related Report
      2017 Annual Research Report
  • [Presentation] 自発的な神経活動に依存した嗅覚神経回路の形成メカニズム2017

    • Author(s)
      竹内春樹、中嶋藍、伊原尚樹、エルドンフ、池谷裕二
    • Organizer
      日本分子生物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] マウス嗅覚系の神経回路の堅牢性に関わる軸索選別分子の発現2017

    • Author(s)
      野仲航司、中嶋藍、伊原尚樹、井ノ口霞、エルドンフ、池谷裕二、竹内春樹
    • Organizer
      日本分子生物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] マウス嗅覚系における活動依存的な神経回路形成機構2017

    • Author(s)
      中嶋藍、伊原尚樹、池谷裕二、竹内春樹
    • Organizer
      日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 嗅神経の自発活動パターンによる回路形成の制御2017

    • Author(s)
      野仲航司、中嶋藍、伊原尚樹、池谷裕二、竹内春樹
    • Organizer
      第17回東京大学生命科学シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Patterned, but not synchronous spontaneous activity of developing olfactory neurons regulates olfactory receptor-specific axon sorting2017

    • Author(s)
      Nakashima Ai, Ihara Naoki, Ikegaya Yuji and Takeuchi Haruki
    • Organizer
      Keystone Symposia “Synapses and Circuits”
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Patterned spontaneous activity regulates OR-specific axon sorting2016

    • Author(s)
      Takeuchi Haruki
    • Organizer
      KoSCL symposium
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Differential expression of axon-sorting molecules in mouse olfactory sensory neurons2016

    • Author(s)
      Takeuchi Haruki, Ihara Naoki, Nakashima Ai and Ikegaya Yuji
    • Organizer
      Society for Neuroscience 2016
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] An instructive role for spontaneous neural acitivity in glomerular map formation2016

    • Author(s)
      Nakashima Ai, Ihara Naoki, Ikegaya Yuji and Takeuchi Haruki
    • Organizer
      CSHL meeting “Axon Guidance, Synapse Formation & Regeneration
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Activity dependent mechanisms of the olfactory map formation2016

    • Author(s)
      Nakashima Ai, Ihara Naoki, Ikegaya Yuji and Takeuchi Haruki
    • Organizer
      ISOT2016 17th International Symposium on Olfaction and Taste
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nrp2+ mitral cells in the main olfactory bulb send axons to the medial amygdala to induce social behaviours2016

    • Author(s)
      Inokuchi K, Takeuchi H, Imamura F, Kim R, Okuno H, Nishizumi H, Bito H, Kikusui T, and Sakano H
    • Organizer
      ISOT2016 17th International Symposium on Olfaction and Taste
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Differential expression of axon-sorting molecules in mouse olfactory sensory neurons2016

    • Author(s)
      Ihara Naoki、Nakashima Ai、Hoshina Naosuke、Ikegaya Yuji、Takeuchi Haruki
    • Organizer
      ISOT2016 17th International Symposium on Olfaction and Taste
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経スパイク列の再構成から迫る活動依存的な嗅覚回路形成機構の解明2016

    • Author(s)
      竹内春樹
    • Organizer
      The 4th Chemosensation and Behavior Workshop
    • Related Report
      2016 Annual Research Report
  • [Presentation] Activity-dependent olfactory neural circuit formation2016

    • Author(s)
      竹内春樹、伊原尚樹、中嶋藍、池谷裕二
    • Organizer
      日本神経科学大会
    • Related Report
      2016 Annual Research Report
  • [Presentation] Differential expression of axon-sorting molecules in mouse olfactory sensory neurons2016

    • Author(s)
      伊原尚樹、中嶋藍、池谷裕二、竹内春樹
    • Organizer
      東京大学生命科学シンポジウム
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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