Functional analysis of the supramammillary nucleus-hippocampal circuits

• Project/Area Number: 17K07043
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Doshisha University (2018-2019); The University of Tokyo (2017)
• Principal Investigator: Hashimotodani Yuki 同志社大学, 研究開発推進機構, 准教授 (50401906)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 海馬 / 乳頭体上核 / 歯状回 / 共放出 / シナプス可塑性 / 光遺伝学 / 神経回路 / 顆粒細胞 / シナプス

Outline of Final Research Achievements

The supramammillary nucleus (SuM) of the hypothalamus projects to the dentate gyrus and the CA2 region of the hippocampus. Although the SuM to hippocampus circuits have been implicated in spatial and emotional memory formation, little is known about precise neural connections between the SuM and hippocampus. By using optogenetics and electrophysiology, we found that the SuM neurons project to both granule cells and GABAergic interneurons and co-release glutamate and GABA. We also found that SuM inputs potentiate granule cell firing when temporally associated with perforant path inputs. These results indicate that the SuM modulates dentate gyrus activity by modulating granule cell outputs.

Academic Significance and Societal Importance of the Research Achievements

乳頭体上核と海馬で形成される神経回路はこれまで記憶や情動に関して重要な役割を果たすことが示唆されてきた。最近はさらに睡眠やナビゲーションにも関わることが報告され、乳頭体上核―海馬間神経回路はより多様な脳機能に寄与することがわかってきた。本研究はこういった重要な脳機能を発揮する神経基盤をシナプスレベルで明らかにした。

Research Products

• [Journal Article] Supramammillary nucleus afferents to the dentate gyrus co-release glutamate and GABA and potentiate granule cell output. (2018)
  • Author(s): Hashimotodani Y, Karube F, Yanagawa Y, Fujiyama F, Kano M
  • Journal Title: Cell Reports Volume: 25 Issue: 10 Pages: 2704-2715
  • DOI: 10.1016/j.celrep.2018.11.016
  • Peer Reviewed / Open Access
• [Journal Article] Near-infrared deep brain stimulation via upconversion nanoparticle-mediated optogenetics. (2018)
  • Author(s): Chen S, Weitemier AZ, Zeng X, He L, Wang X, Tao Y, Huang AJY, Hashimotodani Y, Kano M, Iwasaki H, Parajuli LK, Okabe S, Teh DBL, All AH, Tsutsui-Kimura I, Tanaka KF, Liu X, McHugh TJ.
  • Journal Title: Science Volume: 359 Issue: 6376 Pages: 679-684
  • DOI: 10.1126/science.aaq1144
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] LTP at Hilar Mossy Cell-Dentate Granule Cell Synapses Modulates Dentate Gyrus Output by Increasing Excitation/Inhibition Balance. (2017)
  • Author(s): Hashimotodani Y, Nasrallah K, Jensen KR, Chavez AE, Carrera D, Castillo PE.
  • Journal Title: Neuron Volume: 95 Issue: 4 Pages: 928-943
  • DOI: 10.1016/j.neuron.2017.07.028
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 乳頭体上核―歯状回顆粒細胞シナプスにおける短期可塑性の解析 (2020)
  • Author(s): 田淵詠梨、坂場武史、橋本谷祐輝
  • Organizer: 第97回日本生理学会大会
• [Presentation] Optogenetic characterization of the supramammillary nucleus to the dentate gyrus synaptic connections (2018)
  • Author(s): Yuki Hashimotodani, Yuchio Yanagawa, Masanobu Kano
  • Organizer: 11th FENS Forum of Neuroscience
  • Int'l Joint Research
• [Presentation] 海馬歯状回の再帰性回路におけるシナプス可塑性の役割 (2018)
  • Author(s): 橋本谷祐輝、Pablo E. Castillo
  • Organizer: 第95回日本生理学会
• [Presentation] 乳頭体上核から海馬歯状回への神経投射の解析 (2017)
  • Author(s): 橋本谷祐輝、柳川右千夫、狩野方伸
  • Organizer: 第40回日本神経科学大会