Engineering neural circuits at the single-cell-level by the neuro-plate technique

• Project/Area Number: 17K14620
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Intelligent mechanics/Mechanical systems
• Research Institution: Tohoku University (2018); The University of Tokyo (2017)
• Principal Investigator: Yoshida Shotaro 東北大学, 工学研究科, 助教 (20785349)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 神経科学 / MEMS / パターニング / マイクロ加工 / マイクロマニピュレーション / 神経回路 / バイオMEMS / ブレイン・オン・チップ

Outline of Final Research Achievements

In this study, a method for engineering cultured neural circuits at the single-cell-level has been developed as one of the brain-on-chip technilogies. A microfabricated device was developed that enabled morphological control of a cell body, an axon, and dendrites of single neurons, and manipulation of their position during in vitro cultivation. The morphologically controlled single neurons could be assembled in a neuronal circuit, and synaptic connections as well as synchronized neural activities were observed. The technology will be useful for basic neuroscience research of neural circuit formation and signal transmission for unravelling the mechanisms of brain functions such as memory, learning, and pattern recognition.

Academic Significance and Societal Importance of the Research Achievements

記憶・学習などの脳機能を司る神経回路の情報処理メカニズムは未だ不明な点が多く、多くの研究が為されているものの、精神疾患の根本的な治療や、精密なサイボーグ技術などの開発へは繋がっていない。困難な技術的課題のひとつが、これまでの神経回路の研究は神経細胞の「繋がり方」を制御することができなかったため、ランダムに形成された回路のみを解析対象とせざるを得なかったことである。本研究では神経回路中の要素である単一神経細胞を個別に制御し、選択的に繋げていくという、電子回路工作のように神経回路を構築する技術を開発した。この技術を発展させ、神経回路の解析をより精密に行うことで脳機能の解明を目指せると考えている。

Research Products

• [Int'l Joint Research] University of Freiburg(ドイツ)
• [Journal Article] ３D Arrays of Microcages by Two-photon Lithography for Spatial Organization of Living Cells (2019)
  • Author(s): Florian Larramendy, Shotaro Yoshida, Daniela Maier, Zoltan Fekete, Shoji Takeuchi and Oliver Paul
  • Journal Title: Lab on a Chip Volume: 19 Issue: 5 Pages: 875-884
  • DOI: 10.1039/c8lc01240g
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Assembly and connection of micropatterned single neurons for neuronal network formation (2018)
  • Author(s): Shotaro Yoshida, Midori Kato-Negishi, Shoji Takeuchi
  • Journal Title: Micromachines Volume: 9 Issue: 5 Pages: 235-235
  • DOI: 10.3390/mi9050235
  • Peer Reviewed / Open Access
• [Presentation] Assembly of Micropatterned Neurons for Artificial Neural Network Formation (2017)
  • Author(s): Shotaro Yoshida , Midori Kato-Negishi, and Shoji Takeuchi
  • Organizer: The 1st WPI-IRCN Retreat 2018
• [Remarks] パズルのように神経回路を組み立てる 生きた神経細胞を自在につなぎ、ネットワークを構築
  • URL: https://www.iis.u-tokyo.ac.jp/ja/news/2909/