Ultrastructural analysis of synapse stability

• Project/Area Number: 18K06499
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46020:Anatomy and histopathology of nervous system-related
• Research Institution: Gunma University
• Principal Investigator: Iwasaki Hirohide 群馬大学, 大学院医学系研究科, 教授 (30342752)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: シナプス / 光学顕微鏡 / 電子顕微鏡 / 光-電子相関顕微鏡法 / スパイン / 二光子顕微鏡 / テニューリン / 光―電子相関法

Outline of Final Research Achievements

This project focused on the molecular mechanism of synaptic stabilization. First, dendritic spines of cortical pyramidal neurons were imaged in vivo using two-photon microscopy over time to identify stably maintained spines and newly emerging spines. The same dendrites were then examined by electron microscopy to obtain ultrastructural images of dendritic spines by three-dimensional reconstruction. The results showed that the neck length of the stable spines was almost the same as that of the newly emerged spines, but the spine head of the stable spines was larger and the morphology more complex. In addition, to elucidate the molecular mechanism of synaptic stabilization, we clarified the role of teneurin, a membrane protein involved in synaptic induction.

Academic Significance and Societal Importance of the Research Achievements

脳が長期にわたり安定に記憶を保持するためにはシナプスが長期にわたって安定的に維持される必要がある。一方、新しいことを学習したり外界の変化に応じて柔軟に対応したりするためにはシナプスが可塑的である必要がある。本研究課題では、安定して維持されるスパインの形がどのようなものであるかを明らかにした。スパインの安定性は自閉症などの発達障害や精神疾患とも関連しており、スパインを安定に維持させるしくみの解明や、どのような分子がスパインの安定化に関わっているのかが明らかになれば、発達障害や精神疾患の病因・病態の理解につながるものと期待できる。

Research Products

• [Journal Article] Ultrastructural Observation of Glutamatergic Synapses by Focused Ion Beam Scanning Electron Microscopy (FIB/SEM) (2019)
  • Author(s): Takahashi-Nakazato Ai、Parajuli Laxmi Kumar、Iwasaki Hirohide、Tanaka Shinji、Okabe Shigeo
  • Journal Title: Methods in Molecular Biology Volume: 1941 Pages: 17-27
  • DOI: 10.1007/978-1-4939-9077-1_2
  • ISBN: 9781493990764, 9781493990771
  • Peer Reviewed
• [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
• [Presentation] 走査型電子顕微鏡による樹状突起スパインの三次元再構築 (2018)
  • Author(s): 岩崎広英
  • Organizer: 日本顕微鏡学会
  • Invited