In vivo imaging of astrocytic glutamate dynamics in the brain

• Project/Area Number: 15K18984
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: The University of Tokyo
• Principal Investigator: TAKIKAWA Kenji 東京大学, 大学院医学系研究科(医学部), 客員研究員 (60749274)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: グルタミン酸 / イメージング / in vivo / グリア / アストロサイト / グリア伝達物質

Outline of Final Research Achievements

In vivo analysis of spatiotemporal dynamics of glutamate released from astrocytes in the brain provides an essential information for understanding of astrocyte-mediated synaptic plasticity. For visualizing glutamate dynamics in the vicinity of synapses in the living mouse brain, we aimed to develop an in vivo glutamate imaging system. We first generated a novel optical glutamate sensor, EOS, engineered by position-specific labeling of glutamate-binding protein with a small-molecular fluorescent dye. We then developed methods for specific EOS labeling of neuronal surfaces including synapses. By combining these techniques, we successfully visualized glutamate dynamics around the synapses in vivo in the living mouse cerebral cortex during astrocyte activation. Our in vivo glutamate imaging system should shed light on astrocyte-mediated synaptic plasticity.

Research Products

• [Presentation] In vivo imaging analysis of astrocytic neuroprotective effects in cerebral infarction (2017)
  • Author(s): Hiroshi Sekiya, Kenji Takikawa, Kaname Sato, Miki Takagi, Nami Kitajima, Toshiko Yamazawa, Hirokazu Sakamoto, Shigeyuki Namiki, Kazunori Kanemaru, Kenji F. Tanaka, Kenzo Hirose, Masamitsu Iino
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎ブリックホール(長崎県長崎市)
• [Presentation] 大脳皮質における細胞外ATP動態を可視化するin vivoイメージング技術の開発 (2016)
  • Author(s): 瀧川健司、関谷敬、佐藤要、高木美貴、北島奈美、金丸和典、坂本寛和、並木繁行、山澤徳志子、田中謙二、廣瀬謙造、飯野正光
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-03-10
• [Presentation] 大脳皮質における細胞外ATP動態を可視化するin vivoイメージングシステムの開発 (2015)
  • Author(s): 瀧川健司、関谷敬、佐藤要、北島奈美、高木美貴、金丸和典、坂本寛和、並木繁行、田中謙二、廣瀬謙造、飯野正光
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-07-29
• [Remarks] 東京大学大学院 医学系研究科 細胞分子薬理学教室
  • URL: http://calcium.cmp.m.u-tokyo.ac.jp/index.html
• [Remarks] 東京大学大学院 医学系研究科 脳神経医学専攻 神経生物学教室
  • URL: http://www.neurobiol.m.u-tokyo.ac.jp/