Understanding the design principles of of sleep/wake dynamics in mammals

• Project/Area Number: 26870858
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology / General neuroscience; Animal physiology/Animal behavior
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Sunagawa Genshiro 国立研究開発法人理化学研究所, 多細胞システム形成研究セン ター, 研究員 (70710250)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 睡眠時間 / NMDA / CRISPR / Nr3a / カルシウム / 睡眠恒常性 / SSS / カルシウムイオン / 睡眠 / 覚醒 / 非侵襲

Outline of Final Research Achievements

Two major findings were achieved in this study: (1) Nr3a-KO is a short sleeper, and (2) calcium hyperpolarization pathway is involved in sleep duration regulation in mammals. (1) was achieved by knocking out all members of the NMDA receptor and testing the sleep phenotype in SSS, the snappy sleep stqger, which was developed in this research. (2) was discovered in two steps. In the first step, we created a computational neural model to predict which currents within a neuron are critical for maintaining the type of neural activity associated with slow-wave sleep and the calcium related components became candidates. In the second step, we created twenty-one knockout mice using the developed CRISPR technology, and confirmed that seven genes which was related to calcium dynamics indeed affected sleep duration.

Research Products

• [Journal Article] Involvement of Ca2+-dependent hyperpolarization in sleep duration in mammals (2016)
  • Author(s): Fumiya Tatsuki, Genshiro A. Sunagawa, Shoi Shi, Etsuo A. Susaki, Hiroko Yukinaga, Dimitri Perrin, Kenta Sumiyama, Maki Ukai-Tadenuma, Hiroshi Fujishima, Rei-ichiro Ohno, Daisuke Tone, Koji L. Ode, Katsuhiko Matsumoto, Hiroki R. Ueda
  • Journal Title: Neuron Volume: 印刷中 Issue: 1 Pages: 70-85
  • DOI: 10.1016/j.neuron.2016.02.032
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Mammalian Reverse Genetics without Crossing Reveals Nr3a as a Short-Sleeper Gene. (2016)
  • Author(s): Sunagawa GA, Sumiyama K, Ukai-Tadenuma M, Perrin D, Fujishima H, Ukai H, Nishimura O, Shi S, Ohno R, Narumi R, Shimizu Y, Tone D, Ode KL, Kuraku S, Ueda HR.
  • Journal Title: Cell Rep. Volume: 14 Issue: 3 Pages: 662-677
  • DOI: 10.1016/j.celrep.2015.12.052
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Screening complex organismal level biological systems : sleep and hibernation (2016)
  • Author(s): Genshiro A. Sunagawa.
  • Organizer: SRI Biosciences Division seminar
  • Place of Presentation: SRI・サンフランシスコ・アメリカ
  • Year and Date: 2016-07-29
• [Presentation] Toward hypometabolic organ preservation: the development of stable induction method for mouse torpor. (2016)
  • Author(s): Genshiro A. Sunagawa, Masayo Takahashi.
  • Organizer: The 15th Congress of the Japanese Society for Regenerative Medicine
  • Place of Presentation: 大阪国際会議場・大阪市・大阪府
  • Year and Date: 2016-03-19
• [Presentation] Screening complex biological systems at organismal level: sleep and hibernation. (2016)
  • Author(s): Genshiro A. Sunagawa.
  • Organizer: Kanazawa University Brain/Liver Interface Medicine Research Center Symposium
  • Place of Presentation: 金沢大学・金沢市・石川県
  • Year and Date: 2016-03-07
  • Invited
• [Presentation] Next-generation Sleep Phenotyping System for Mice. (2015)
  • Author(s): Genshiro A. Sunagawa, Hiroki R. Ueda.
  • Organizer: The 38th Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: 国際会議場・神戸市・兵庫県
  • Year and Date: 2015-07-30
• [Presentation] Next-generation Sleep Phenotyping System for Mice. (2014)
  • Author(s): Genshiro A. Sunagawa
  • Organizer: Homeodynamics in Clocks, Sleep and Metabolism, TOKYO TRANSLATIONAL THERAPEUTICS MEETING
  • Place of Presentation: Ito Hall, Ito International Research Center, The University of Tokyo
  • Year and Date: 2014-09-24
• [Remarks] 次世代型逆遺伝学による睡眠遺伝子Nr3aの発見
  • URL: http://www.riken.jp/pr/press/2016/20160108_1/
• [Remarks] なぜ私たちは眠るか ～眠りの素は細胞内カルシウム？～
  • URL: http://www.jst.go.jp/pr/announce/20160318/