Exploration of a new pathway of light transmission to the deep brain

• Project/Area Number: 20K21416
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 44:Biology at cellular to organismal levels, and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Nagata Takashi 東京大学, 物性研究所, 助教 (90589962)
• Project Period (FY): 2020-07-30 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2022: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2020: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
• Keywords: 光受容 / 脳深部 / 光生物学 / 視神経

Outline of Research at the Start

哺乳類などの脳の深部領域には光センサータンパク質を持つ光感受性の細胞が存在しているが、どのように光が到達するのかはよくわかっていない。本研究では脳深部へ光を伝達し得る新たな経路の候補として視神経に着目する。視神経は眼の中の網膜から脳深部へと伸びており、光ファイバーに類似した構造を持つため、光が効率よく伝達される可能性が考えられる。この可能性を検証するため、マウス等の視神経の光伝達効率の評価や、実際に視神経を通って脳深部に到達する光の定量的解析を行う。

Outline of Final Research Achievements

Many vertebrates, including mammals, express the photosensitive protein opsins in the deep brain regions, suggesting that "brain photoreception" by cells with light-sensing functions takes place. However, it has been questioned whether light can reach the deep brain, especially in mammals, because light from the surface of the head is reflected, absorbed, and scattered by hair, skin, skull, and brain tissue. In this research project, the possibility was examined that light is transmitted to the deep brain by a pathway through the eyes. An experimental system that can measure light intensity and spectrum in deep brain regions was newly constructed and light intensity was measured at a deep brain region when light was incident from the eyes of mice. The results showed that light was more efficiently transmitted to the deep brain via the eyes than through the skin and cranium.

Academic Significance and Societal Importance of the Research Achievements

近年の研究により、マウスなどにおいて脳深部に発現するオプシンが光依存的に体温の調節や体の活動レベルの制御に関わっていることが明らかになりつつある。本研究により脳深部への効率的な光経路の候補が明らかになったことで、光が動物の生理機能に与える影響を理解するために、脳内での光受容の研究が更に重要になると考えられる。またヒトの脳も光に応答して様々な生理的変化を引き起こすことが既に知られており、将来的にヒトにおいても同じ光経路が明らかになれば、医学的な観点からも大きな波及効果につながる可能性がある。

Research Products

• [Journal Article] Reversible Photoreaction of a Retinal Photoisomerase, Retinal G Protein-Coupled Receptor RGR (2023)
  • Author(s): Naoya Morimoto, Takashi Nagata, Keiichi Inoue
  • Journal Title: Biochemistry Volume: 62 Issue: 9 Pages: 1429-1432
  • DOI: 10.1021/acs.biochem.3c00084
  • Peer Reviewed
• [Journal Article] Rhodopsin-bestrophin fusion proteins from unicellular algae form gigantic pentameric ion channels (2022)
  • Author(s): Rozenberg A,Kaczmarczyk I,Matzov D,Vierock J,Nagata T,Sugiura M,Katayama K,Kawasaki Y,Konno M,Nagasaka Y,Aoyama M,Das I,Pahima E,Church J,Adam S,Borin VA,Chazan A,Augustin S,Wietek J,Dine J,Peleg Y,Kawanabe A,Fujiwara Y,Yizhar O,Sheves M,Schapiro I,Furutani Y,Kandori H,Inoue K,Hegemann P,Beja O,Shalev-Benami M.
  • Journal Title: Nature Structural & Molecular Biology Volume: 29 Issue: 6 Pages: 592-603
  • DOI: 10.1038/s41594-022-00783-x
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Rhodopsins at a Glance (2021)
  • Author(s): Takashi Nagata, Keiichi Inoue
  • Journal Title: Journal of Cell Science Volume: 134 Issue: 22
  • DOI: 10.1242/jcs.258989
  • Peer Reviewed