Optical imaging of neural plasticity from freely moving animal

• Project/Area Number: 16K06993
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Kyoto University
• Principal Investigator: Yawata Satoshi 京都大学, 医学研究科, 特定助教 (90455246)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: イメージング / 内視鏡 / 線条体 / 可塑性 / 大脳基底核 / 細胞内シグナル

Outline of Final Research Achievements

Candidate mechanisms of memory and learning are neural plasticity, including changes in the connection between neurons, and changes in the intrinsic excitability. Recently, Forster resonance energy transfer (FRET) bioprobes are developed and widely recognized as powerful tools to measure the activity of intracellular signaling molecules related to neural plasticity. These FRET probes enable us to visualize plasticity, but measuring systems are poorly established.
In this study, I developed novel optical imaging system for FRET biosensor to visualize “neural plasticity” from a “deep brain area” of “freely-moving animal” with “single cellular resolution”. Furthermore, the measurement of “neural activity” by Ca2+ imaging could be performed simultaneously. Using this novel imaging technique, I observed neural activity and ERK activity from medium spiny neurons in dorsal striatum during visual discrimination task.

Academic Significance and Societal Importance of the Research Achievements

本研究において、自由行動中動物から「可塑性」と「神経活動」を同時にイメージングできる新しい計測技術の開発を行った。記憶や学習の獲得において、いつ、どのような神経細胞で、どのような可塑性により、どのように神経情報が修飾・修正されていくかを観察することが可能となった。
また、この技術は細胞内シグナル分子の活性を生体内からリアルタイムに計測できる技術であり、神経の情報処理機構の解明においてのみならず、病態モデルマウスの解析や薬物動態の解析にも利用可能な重要な技術である。

Research Products

• [Journal Article] Repeated social defeat stress impairs attentional set shifting irrespective of social avoidance and increases female preference associated with heightened anxiety (2018)
  • Author(s): Higashida Shu、Nagai Hirotaka、Nakayama Kazuki、Shinohara Ryota、Taniguchi Masayuki、Nagai Midori、Hikida Takatoshi、Yawata Satoshi、Ago Yukio、Kitaoka Shiho、Narumiya Shuh、Furuyashiki Tomoyuki
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 10454-10454
  • DOI: 10.1038/s41598-018-28803-1
  • NAID: 120006501224
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] In vivo calcium imaging from dentate granule cells with wide-field fluorescence microscopy (2017)
  • Author(s): Hayashi Yuichiro、Yawata Satoshi、Funabiki Kazuo、Hikida Takatoshi
  • Journal Title: PLOS ONE Volume: 12 Issue: 7 Pages: e0180452-e0180452
  • DOI: 10.1371/journal.pone.0180452
  • NAID: 120006539578
  • Peer Reviewed / Open Access
• [Journal Article] Calcium dysregulation contributes to neurodegeneration in FTLD patient iPSC-derived neurons (2016)
  • Author(s): Imamura, K., Sahara, N., Kanaan, N. M., Tsukita, K., Kondo, T., Kutoku, Y., Ohsawa, Y., Sunada, Y., Kawakami, K., Hotta, A., Yawata, S., Watanabe, D., Hasegawa, M., Trojanowski, J. Q., Lee, V. M.-Y., Suhara, T., Higuchi, M., and Inoue, H.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 34904-34904
  • DOI: 10.1038/srep34904
  • NAID: 120005850272
  • Peer Reviewed / Open Access / Int'l Joint Research