Development of whole-brain imaging system for spatial and temporal activation mapping

• Project/Area Number: 18K19498
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 51:Brain sciences and related fields
• Research Institution: Osaka University
• Principal Investigator: Kaoru Seiriki 大阪大学, 薬学研究科, 招へい教員 (90802918)
• Project Period (FY): 2018-06-29 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 共焦点顕微鏡 / イメージング / 脳 / 神経細胞 / 神経科学 / 薬理学

Outline of Final Research Achievements

This study aimed to establish a method for whole-brain imaging analysis of neurons activated by environmental stimuli and labeled with multicolor fluorescent proteins. We modified the imaging system FAST (block-FACE Serial microscopy Tomography) for multicolor imaging and published a detailed protocol paper including the implementation of multicolor imaging and image processing. We also generated transgenic mice with a drug-inducible gene expression system under the control of the Fos promoter. By combination with adeno-associated virus vector-mediated gene transfer, we achieved activity- and drug-dependent labeling of neurons.

Academic Significance and Societal Importance of the Research Achievements

ストレス等の経験による脳機能の適応、機能変調の機序をより詳細に理解するためには、広範な脳領域を対象として領域間の神経活動の相関性を解析し、その経験依存的な変化を細胞レベルで検出する必要があると考えられる。しかし、同時に解析可能な脳領域の範囲と時間の分解能が限られる等の技術的制限等があり、現時点では複数のタイムポイントにおいて活動した細胞の脳内分布や軸索投射の違いを解析することは容易ではない。そのイメージング解析法の確立を目指した本研究は、経験依存的な脳機能の制御機構や脳神経疾患モデルにおける脳機能の変調過程を細胞レベルで解析する研究に貢献可能であり、学術的・社会的意義があると考えられる。

Research Products

• [Journal Article] Whole-brain block-face serial microscopy tomography at subcellular resolution using FAST. (2019)
  • Author(s): Seiriki K, Kasai A, Nakazawa T, Niu M, Naka Y, Tanuma M, Igarashi H, Yamaura K, Hayata-Takano A, Ago Y, Hashimoto H.
  • Journal Title: Nat Protoc. Volume: 印刷中 Issue: 5 Pages: 1509-1529
  • DOI: 10.1038/s41596-019-0148-4
  • Peer Reviewed / Open Access
• [Journal Article] Whole-brain block-face serial microscopy tomography at subcellular resolution using FAST (2019)
  • Author(s): Seiriki K, Kasai A, Nakazawa T, Niu M, Naka Y, Tanuma M, Igarashi H, Yamaura K, Hayata-Takano A, Ago Y, Hashimoto H
  • Journal Title: Nature Protocols Volume: 印刷中
  • Peer Reviewed
• [Presentation] Whole-brain mapping of activated neurons and circuits in brains after exposure to acute stressors (2021)
  • Author(s): Misaki Niu, Atsushi Kasai, Kaoru Seiriki, Hitoshi Hashimoto
  • Organizer: 第９４回日本薬理学会年会
• [Presentation] Whole-brain mapping analysis of neuronal activation elicited by single and repeated defeat stress relevant to stressi ntensity dependent behavioral alteration (2020)
  • Author(s): Kaoru Seiriki, Shunsuke Maeda, Yumi Hirato, Atsushi Kasai, Hitoshi Hashimoto
  • Organizer: 第６３回日本神経化学会大会
• [Presentation] High-speed and scalable whole-brain imaging for finding singularity in the brain (2019)
  • Author(s): Kaoru Seiriki, Atsushi Kasai, Takanobu Nakazawa, Hitoshi Hashimoto
  • Organizer: Neuro 2019
• [Presentation] 高精細全脳イメージング技術FASTの開発と精神疾患モデルマウスの病態解析 (2018)
  • Author(s): 勢力薫、笠井淳司、丹生光咲、田沼将人、五十嵐久人、中澤敬信、山口瞬、井上謙一、高田昌彦、橋本均
  • Organizer: 第68回日本薬学会近畿支部総会・大会