PKN1 regulates metaplasticity in hippocampus

• Project/Area Number: 23500461
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology and muscle physiology
• Research Institution: Gunma University
• Principal Investigator: YASUDA Hiroki 群馬大学, 医学(系)研究科(研究院), 准教授 (60294071)
• Co-Investigator(Renkei-kenkyūsha): MUKAI Hideyuki 神戸大学, 大学院医学研究科, 准教授 (80252758) ; KOJIMA Nobuhiko 東洋大学, 生命科学部, 教授 (80215251)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: protein kinase N / 代謝型グルタミン酸受容体 / グルタミン酸トランスポーター / シナプス可塑性 / ストレス / 海馬 / PKN1 / メタ可塑性 / 神経発達 / PKN / 海馬歯状回 / 顆粒細胞

Outline of Final Research Achievements

I investigated the roles of protein kinase N1 (PKN1) using PKN1a knockout mice and found that PKN1 activates neuronal glutamate transporter (EAAT3), reduces synaptic and extracellular glutamate, and normalizes metabotropic glutamate receptor (mGluR) function. PKN1 suppresses unnecessary mGluR5-dependent long-term depression (LTD) of glutamate synaptic transmission in the developing hippocampus. Stress ihibited EAAT3 presumably through reducing PKN1 activity and elevates neuronal excitability. So elevating PKN1 activity could activate EAAT3 and reduce epileptic neuronal activity.
I also found that priming of glutamate synaptic transmission by prior acitivity was induced in wild-type mice but that the priming was not induced in PKN1a KO mice, suggesting that PKN1 is needed in priming of excitatory synaptic transmission.

Research Products

• [Journal Article] Turning off of GluN2B subunits and turning on of CICR in hippocampal LTD induction after developmental GluN2 subunit switch. (2015)
  • Author(s): Hiroki Yasuda and Hideyuki Mukai
  • Journal Title: Hippocampus Volume: 未定 Issue: 11 Pages: 1274-1284
  • DOI: 10.1002/hipo.22435
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Elfn1 recruits presynaptic mGluR7 in trans and its loss results in seizures. (2014)
  • Author(s): Naoko H. Tomioka, Hiroki Yasuda, Hiroyuki Miyamoto, Minoru Hatayama, Naoko Morimura, Yoshifumi Matsumoto, Toshimitsu Suzuki, Maya Odagawa, Yuri S. Odaka, Yoshimi Iwayama, Ji Won Um, Jaewon Ko, Yushi Inoue, Sunao Kaneko, Shinichi Hirose, Kazuyuki Yamada, Takeo Yoshikawa, Kazuhiro Yamakawa, Jun Aruga
  • Journal Title: Nature Communications Volume: 5 Issue: 1 Pages: 45011-16
  • DOI: 10.1038/ncomms5501
  • Peer Reviewed / Open Access
• [Journal Article] Selective control of inhibitory synapse development by Slitrk3-PTPδ trans-synaptic interaction (2012)
  • Author(s): Hideto Takahashi, Kei-ichi Katayama, Kazuhiro Sohya, Hiroyuki Miyamoto, Tuhina Prasad, Yoshifumi Matsumoto, Maya Ota, Hiroki Yasuda, Tadaharu Tsumoto, Jun Aruga, Ann Marie Craig
  • Journal Title: Nature Neuroscience Volume: 15 Issue: 3 Pages: 389-398
  • DOI: 10.1038/nn.3040
  • Peer Reviewed
• [Journal Article] Frequent spontaneous seizures followed by spatial working memory/anxiety deficits in mice lacking sphingosine 1-phosphate receptor 2 (2011)
  • Author(s): Noriyuki Akahoshi, Yasuki Ishizaki, Hiroki Yasuda, Yoshiya L.Murashima, Toshikazu Shinba, Kaoru Goto, Toshiyuki Himi, Jerold Chun, Isao Ishii
  • Journal Title: Epilepsy & Behavior Volume: 22 Issue: 4 Pages: 659-665
  • DOI: 10.1016/j.yebeh.2011.09.002
  • Peer Reviewed
• [Presentation] Elfn1はmGluR7をシナプス前部に集積させ、てんかんや多動症の発症に関与する (2014)
  • Author(s): 富岡 直子, 安田 浩樹, 宮本 浩行, 山田 一之, 吉川 武男, 山川 和弘, 有賀 純
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜 （神奈川県横浜市）
  • Year and Date: 2014-11-26
• [Presentation] Myosin II ATPase activity mediates the biphasic movement of stable F-actin bound by drebrin A between dendritic spines and the parent dendrite in long-term potentiation. (2014)
  • Author(s): Tomoaki Shirao, Toshiyuki Mizui, Noriko Koganezawa, Hideo Shimizu, Hiroki Yasuda, Yuko Sekino
  • Organizer: Neuroscience 2014 (44th Annual Meeting of the Society for Neuroscience)
  • Place of Presentation: The Walter E. Washington Convention Center (Washington, DC, USA)
  • Year and Date: 2014-11-19
• [Presentation] Elfn1 recruits presynaptic mGluR7 in trans and its loss cause epilepsy, hyperactivity, and attention deficit. (2014)
  • Author(s): J. ARUGA, N. H. TOMIOKA, H. YASUDA, H. MIYAMOTO
  • Organizer: Neuroscience 2014 (44th Annual Meeting of the Society for Neuroscience)
  • Place of Presentation: The Walter E. Washington Convention Center (Washington, DC, USA)
  • Year and Date: 2014-11-16
• [Presentation] PSD-Zip70によるRap2活性調節を介したシナプス形成制御 (2014)
  • Author(s): 真柳 平, 安田 浩樹, 祖父江 憲治
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館 （京都府京都市）
  • Year and Date: 2014-10-16
• [Presentation] グルタミン酸トランスポーターを介したPKN1による代謝型グルタミン酸受容体機能制御 (2014)
  • Author(s): 安田 浩樹、山本 光、川又 敏夫、向井秀幸
  • Organizer: 第37回日本神経科学学会
  • Place of Presentation: パシフィコ横浜 （神奈川県横浜市）
  • Year and Date: 2014-09-11
• [Presentation] REGULATORY ROLE OF DREBRIN IN HIPPOCAMPUSDEPENDENT LEARNING (2011)
  • Author(s): Shirao, T., Hanamura, K., Yasuda, H., Kajita, Y., Kamata, Y., Sekino, Y. and Kojima, N.
  • Organizer: ISN-ESN-2011 (International Society for Neurochemistry and European Society for Neurochemistry) 23rd Biennial Meeting
  • Place of Presentation: Athens, Greece
• [Presentation] Lrfn2/SALM1 による海馬興奮性シナプスの機能制御とその遺伝子欠損マウスにみられた行動異常 (2011)
  • Author(s): 守村 直子 安田 浩樹 山田 一之 富岡 直子 片山 圭一 山口 和彦 太田 摩耶 神谷 明子 有賀 純
  • Organizer: 第34回日本神経科学学会
  • Place of Presentation: パシフィコ横浜 (神奈川県)
• [Presentation] 発達期海馬長期抑圧誘発におけるカルシウムソースのスイッチ (2011)
  • Author(s): 安田 浩樹
  • Organizer: 第34回日本神経科学学会
  • Place of Presentation: パシフィコ横浜 (神奈川県)
• [Presentation] マウス脳におけるドレブリンアイソフォームの特異的分布と機能
  • Author(s): 児島 伸彦、安田 浩樹、花村 健次、白尾 智明
  • Organizer: 第35回日本神経科学学会
  • Place of Presentation: 名古屋
• [Presentation] Lrfn2/SALM1-deficient mice show neuropsychiatric disorder-like behavior phenotypes and synaptic changes of hippocampus
  • Author(s): N. MORIMURA, H. YASUDA, K. YAMAGUCHI, K.-I. KATAYAMA, K. YAMADA, N. TOMIOKA, M. OTA, J. ARUGA
  • Organizer: Neuroscience 2012 (42nd Annual Meeting of the Society for Neuroscience)
  • Place of Presentation: New Orleans, USA
• [Book] Protein Kinase Technologies, Neuromethods vol.68 (2012)
  • Author(s): Hiroki Yasuda and Hideyuki Mukai
  • Total Pages: 12
  • Publisher: Springer
• [Remarks]
  • URL: http://ercgsm.dept.med.gunma-u.ac.jp/?page_id=541