Development of the technique to promote synapse maturation using DREADD system.

• Project/Area Number: 24650183
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Shinshu University (2013-2014); National Institute for Physiological Sciences (2012)
• Principal Investigator: TABUCHI Katsuhiko 信州大学, 学術研究院医学系, 教授 (20546767)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: シナプス / 神経実験形態学

Outline of Final Research Achievements

To overcome disorders caused by deficit of synapse maturation, such as autism, we attempted to promote synapse maturation using DREADD system. For this, we introduced one type of DREADD, hM3Dq, into layer II/III pyramidal neurons in cerebral cortex in mouse brains, followed by administration of CNO to induce hM3Dq signal. We found that the synapse maturation was promoted in the hM3Dq expressing neurons judged from the morphology of dendritic spines. Furthermore, we found that this signal induced serine phosphorylation in the cytoplasmic region of Neurexin-1 that was known to be involved in synapse maturation, due to the activation of PKC.

Research Products

• [Journal Article] PTPσ functions as a presynaptic receptor for the glypican-4/LRRTM4 complex and is essential for excitatory synaptic transmission. (2015)
  • Author(s): Ko JS, Pramanik G, Um JW, Shim JS, Lee D, Kim KH, Chung GY, Condomitti G, Kim HM, Kim H, de Wit J, Park KS, Tabuchi K, Ko J.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 112(6) Issue: 6 Pages: 1874-1879
  • DOI: 10.1073/pnas.1410138112
  • Peer Reviewed / Open Access
• [Journal Article] Enhanced synapse remodeling as a common phenotype in mouse models of autism. (2014)
  • Author(s): Isshiki, M., Tanaka, S., Kuriu, T., Tabuchi, K., Takumi, T. and Okabe, S.
  • Journal Title: Nat. Commun. Volume: 5 Issue: 1 Pages: 4742-4742
  • DOI: 10.1038/ncomms5742
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Calsyntenins function as synaptogenic adhesion molecules in concert with neurexins. (2014)
  • Author(s): Um JW, Pramanik G, Ko JS, Song MY, Lee D, Kim H, Park KS, Sudhof TC, Tabuchi K, Ko J.
  • Journal Title: Cell Rep Volume: 6(6) Issue: 6 Pages: 1096-1109
  • DOI: 10.1016/j.celrep.2014.02.010
  • Peer Reviewed
• [Journal Article] Neuroliginモデルマウスに見るシナプス成熟障害と自閉症との関係（総説） (2014)
  • Author(s): 田渕克彦, 張文欣, Nur Farehan Mohamed Asgar, Gopal Pramanik
  • Journal Title: 日本神経精神薬理学雑誌 Volume: Vol.34 No.1 Pages: 1-4
• [Journal Article] シナプスと自閉症（総説） (2014)
  • Author(s): 田渕克彦
  • Journal Title: 生体の科学 Volume: Vol.65. No.1 Pages: 3-6
• [Journal Article] Presynaptic neurexin-3 alternative splicing trans-synaptically controls postsynaptic AMPA receptor trafficking. (2013)
  • Author(s): Aoto J, Martinelli DC, Malenka RC, Tabuchi K, Sudhof TC.
  • Journal Title: Cell Volume: 154(1) Issue: 1 Pages: 75-88
  • DOI: 10.1016/j.cell.2013.05.060
  • Peer Reviewed
• [Journal Article] ニューレグリン受容体（ERBB4）の異常と精神疾患（総説） (2013)
  • Author(s): 田渕克彦
  • Journal Title: 生体の科学 Volume: Vol.64 No.5 Pages: 470-471
• [Journal Article] Neuroligin-1 controls synaptic abundance of NMDA-type glutamate receptors through extracellular coupling (2013)
  • Author(s): Fukazawa Y(他10名)
  • Journal Title: Proc Natl Acad Sci USA Volume: 110 Issue: 2 Pages: 725-730
  • DOI: 10.1073/pnas.1214718110
  • Peer Reviewed
• [Journal Article] Analysis of Neuroligin-3 R451C knock-in mice as models for autistic savant. (2012)
  • Author(s): Deeba Noreen Baig, Toru Yanagawa, Katsuhiko Tabuchi
  • Journal Title: Japanese Journal of Biological Psychiatry Volume: 23(4) Pages: 281-286
  • NAID: 130005395429
• [Presentation] Neuroligin-3変異マウスを用いた非症候群性自閉症におけるシナプス異常の研究 (2015)
  • Author(s): 田渕克彦
  • Organizer: 第92回日本生理学会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-03-23
  • Invited
• [Presentation] Impairment in Synapse Maturation as a Cause of Autism. (2014)
  • Author(s): Katsuhiko Tabuchi
  • Organizer: International Conference on Emerging Trends in Life Sciences for Sustainable Development.
  • Place of Presentation: Forman Christian College, Lahore, Pakistan
  • Year and Date: 2014-10-09
  • Invited
• [Presentation] Neuroliginモデルマウスに見る (2013)
  • Author(s): 田渕克彦
  • Organizer: 第55回脳の医学生物学研究会
  • Place of Presentation: 名古屋市立大学医学部（愛知県名古屋市）
  • Invited
• [Presentation] Synapse maturation and autism: The role of synapse adhesion molecules (2013)
  • Author(s): 田渕 克彦
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: タワーホール船堀（東京都）
  • Invited
• [Presentation] Synapse function and autism: The role of Neuroligins and Neurexins (2012)
  • Author(s): Katsuhiko Tabuchi
  • Organizer: 15th Annual Neuroscience Symposium The Korean Society for Brain and Neural Science
  • Place of Presentation: ソウル国立大学（韓国）
  • Invited
• [Presentation] Analysis of Neuroligin mouse models relevant to pathophysiology of autism. (2012)
  • Author(s): 田渕 克彦
  • Organizer: 第３４回日本生物学的精神医学会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Invited
• [Presentation] Synapse maturation and autism: The role of Neuroligins and Neurexins (2012)
  • Author(s): Katsuhiko Tabuchi
  • Organizer: The 11th Biennial Meeting of the Asia Pacific Society for Neurochemistry
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Invited
• [Remarks] 信州大学医学部分子細胞生理学教室
  • URL: http://www.shinshu-u.ac.jp/faculty/medicine/chair/i-2seiri/ja/tabuchi.html
• [Remarks] 自然科学研究機構生理学研究所 田渕克彦
  • URL: http://www.nips.ac.jp/dcs/member_tabuchi.html