Cell-type-specific patterned activities specify gene expression patterns for olfactory circuit formation

• Project/Area Number: 18K14712
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Nakashima Ai 東京大学, 大学院薬学系研究科(薬学部), 特任助教 (60706331)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 嗅覚 / 発生 / 神経活動 / 回路形成 / 嗅覚系 / 神経回路構築

Outline of Final Research Achievements

During development, axons from various olfactory neurons expressing the same olfactory receptor (OR) segregate into specific glomeruli in an activity-dependent manner. We found that OSNs exhibited OR-specific temporal patterns of spontaneous activities. Moreover, differing patterns of neuronal activity induced different expression patterns of axon-sorting molecules that regulate glomerular segregation. We propose an activity-dependent mechanism that is fundamentally different from the Hebbian plasticity theory in which cell-type-specific patterned activity contributes to generating the combinatorial code of axon-sorting molecules for the olfactory map refinement.

Academic Significance and Societal Importance of the Research Achievements

発達期における神経細胞の適切な活動とそれに伴う回路の成熟は、その後の我々の高度な行動・機能発現に極めて重要な役割を果たすことが知られている。したがって、その機構の解明は神経科学における重要なテーマの一つである。本研究課題の成果は、神経活動依存的な回路形成の新奇メカニズムの存在を意味しており、嗅覚系のみならず他の脳領域においても複雑なネットワークを構築する仕組みとして敷衍できる可能性があると期待される。

Research Products

• [Journal Article] Structured spike series specify gene expression patterns for olfactory circuit formation. (2019)
  • Author(s): Nakashima, A., Ihara, N., Shigeta, M., Kiyonari, H., Ikegaya, Y., Takeuchi, H.
  • Journal Title: Science Volume: 365(6448) Issue: 6448
  • DOI: 10.1126/science.aaw5030
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Sharp wave-associated activity patterns of olfactory cortical neurons in the mouse piriform cortex (2018)
  • 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
  • Peer Reviewed
• [Presentation] Structured spike series specify gene expression patterns for olfactory circuit formation (2019)
  • 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
  • Int'l Joint Research
• [Presentation] The temporal pattern of neuronal activity rather than its synchronicity refines olfactory codes in the brain (2019)
  • Author(s): Nakashima, A., Ihara, N., Ikegaya, Y., Takeuchi, H.
  • Organizer: The 48th Naito Conference
  • Int'l Joint Research
• [Presentation] Cell-type-specific patterned activities specify gene expression patterns for olfactory circuit formation (2019)
  • Author(s): Nakashima, A., Ihara, N., Ikegaya, Y., Takeuchi, H.
  • Organizer: ISMNTOP/YRUF/AISCRIB2019
  • Int'l Joint Research
• [Presentation] 嗅神経回路形成のメカニズム (2019)
  • Author(s): 中嶋藍、伊原尚樹、池谷裕二、竹内春樹
  • Organizer: 第140回日本薬理学会関東部会シンポジウム・次世代薬理学セミナー
• [Presentation] 神経活動パターン依存的な嗅覚回路形成 (2019)
  • Author(s): 中嶋藍、伊原尚樹、池谷裕二、竹内春樹
  • Organizer: 第42回日本神経科学大会
  • Int'l Joint Research
• [Presentation] 神経活動パターン依存的な嗅覚神経回路の形成機構 (2019)
  • Author(s): 伊原尚樹、中嶋藍、池谷裕二、竹内春樹
  • Organizer: 日本味と匂学会第53回大会
• [Presentation] 嗅覚梨状皮質の細胞種分類 (2019)
  • Author(s): 中嶋藍、伊原直樹、香取和生、池谷裕二、竹内春樹
  • Organizer: 第53回日本味と匂学会
• [Presentation] 神経活動パターンに依存した嗅覚神経回路の形成機構 (2019)
  • Author(s): 伊原尚樹、中嶋藍、池谷裕二、竹内春樹
  • Organizer: 日本薬学会第140年会
• [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
• [Presentation] A non-Hebbian activity-dependent mechanism underlying olfactory circuit formation (2018)
  • 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
• [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
• [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」
• [Presentation] Patterned, but not synchronous spontaneous activity of developing olfactory neurons regulates olfactory receptor-specific axon sorting (2018)
  • Author(s): Takeuchi H, Nakashima A, Ihara N and Ikegaya Y
  • Organizer: Cold Spring Harbor Laboratory Meeting: Molecular Mechanisms of Neuronal Connectivity
• [Presentation] Sequential activities of cortical neurons in the mouse piriform cortex during sharp wave (2018)
  • Author(s): Katori, K., Manabe, H., Nakashima, A., Sasaki, T., Ikegaya, Y., Takeuchi H
  • Organizer: Cold Spring Harbor Asia Conference
• [Presentation] Patterned, but not synchronous spontaneous activity of developing olfactory neurons regulates olfactory receptor-specific axon sorting (2018)
  • Author(s): Takeuchi H, Nakashima A, Ihara N and Ikegaya Y
  • Organizer: Gordon Research Conference: Molecular and Cellular Neurobiology
• [Presentation] A Combinatorial expression of axon-sorting molecules ensures robustness to neural activity changes for neural map formation in the mouse olfactory system (2018)
  • Author(s): Ihara N, Nakashima A, Nonaka K, Ihara N, Ikegaya Y, and Takeuchi H
  • Organizer: Gordon Gordon Research Conference: Molecular and Cellular Neurobiology
• [Presentation] Patterned, but not synchronous spontaneous activity of developing olfactory neurons regulates olfactory receptor-specific axon sorting (2018)
  • Author(s): Nakashima A, Ihara N, Ikegaya Y, Takeuchi H
  • Organizer: 22nd Biennial Meeting of the International Society of Developmental Neuroscience
• [Remarks] トピックス：神経回路形成の新たなルールを解明
  • URL: http://www.f.u-tokyo.ac.jp/topics.html?page=3&key=1560141523