Roles of endocannabinoid-dependent plasticity in anti-epileptic effects

• Project/Area Number: 15K18331
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology / General neuroscience
• Research Institution: The University of Tokyo
• Principal Investigator: Hashimotodani Yuki 東京大学, 大学院医学系研究科(医学部), 助教 (50401906)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 海馬歯状回 / 苔状細胞 / 内因性カンナビノイド / シナプス可塑性 / LTP / 海馬 / てんかん / 顆粒細胞 / LTD / CB1受容体

Outline of Final Research Achievements

In the dentate gyrus of hippocampus, excitatory mossy cells and granule cells make reciprocal connections. It is known that these circuits are important for anti-epileptic effects through CB1 receptor activation. It is expected that CB1 receptor-dependent form of synaptic plasticity may contribute to this effect. However, precise mechanisms are still unclear. Here, we examined whether mossy cell-granule cell synapses shows any kinds of long-term synaptic plasticity. By using electrophysiological and optogenetic methods, we found that this synapse exhibited both LTD and LTP. We further found that this LTP requires presynaptic cAMP/PKA signaling. How these long-term synaptic plasticities contribute to anti-epileptic effects will be investigated in the future study.

Research Products

• [Journal Article] Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders (2016)
  • Author(s): Nakazawa T, Hashimoto R, Sakoori K, Sugaya Y, Tanimura A, Hashimotodani Y, Ohi K, Yamamori H, Yasuda Y, Umeda-Yano S, Kiyama Y, Konno K, Inoue T, Yokoyama K, Inoue T, Numata S, Ohnuma T, Iwata N, Ozaki N, Hashimoto H, Watanabe M, Manabe T, Yamamoto T, Takeda M, Kano M.
  • Journal Title: Nat Communications Volume: 7 Issue: 1 Pages: 10594-10594
  • DOI: 10.1038/ncomms10594
  • NAID: 120006535052
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 海馬歯状回局所回路におけるシナプス可塑性 (2016)
  • Author(s): 橋本谷祐輝
  • Organizer: 第21回グリアクラブ
  • Place of Presentation: 小樽朝里クラッセホテル（北海道小樽市）
  • Year and Date: 2016-02-01