Functional significance of input pathway- and cell type-dependent accumulation of non-synaptic NR3A

• Project/Area Number: 17K08503
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Hokkaido University
• Principal Investigator: Yamasaki Miwako 北海道大学, 医学研究院, 准教授 (10431305)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: NMDA受容体 / シナプス / 小脳 / 神経科学

Outline of Final Research Achievements

The localization and physiological function of NMDA receptor subunit NR3A remain largely unexplored. In the present study, we found that NR3A was selectively localized to non-synaptic contacts between climbing fiber to cerebellar stellate cells, and those between glutamatergic terminals and somatostatin-positive GABAergic interneurons in the cerebral cortex. At such contacts, NR3A colocalized with NR1 and Kv4.3. To identify molecular partners that constitute biochemical complex, we immunopurified biochemical complex containing NR3A. We found that NR1 but not Kv4.3 was included in the complex. NR3A knockout mouse showed no evident motor discoordination or histological abnormality.

Academic Significance and Societal Importance of the Research Achievements

脳機能を担う神経回路の発達においてNMDA型グルタミン酸受容体NR3Aは重要な役割を持つが、発現部位やその機能に不明な点が多く解明が期待されている。本研究では、NR3A受容体は他の受容体とは全く異なり、グルタミン酸作動性神経終末の作る非シナプス性結合選択的に、NR1や早期不活性化Kチャネルkv4.3と共に集積することを見出した。このユニークな知見は今後の脳回路研究の発展に貢献することが期待される。

Research Products

• [Int'l Joint Research] Yale大学(米国)
• [Int'l Joint Research] Yale大学(米国)
• [Int'l Joint Research] Edinburgh大学(英国)
• [Int'l Joint Research] Khon Kaen大学(タイ)
• [Int'l Joint Research] Yale大学・医学部(米国)
• [Journal Article] Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain (2019)
  • Author(s): Nakamoto Chihiro、Konno Kohtarou、Miyazaki Taisuke、Nakatsukasa Ena、Natsume Rie、Abe Manabu、Kawamura Meiko、Fukazawa Yugo、Shigemoto Ryuichi、Yamasaki Miwako、Sakimura Kenji、Watanabe Masahiko
  • Journal Title: Journal of Comparative Neurology Volume: 528 Issue: 6 Pages: 1003-1027
  • DOI: 10.1002/cne.24792
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] mGluR1 in cerebellar Purkinje cells is essential for the formation but not expression of associative eyeblink memory (2019)
  • Author(s): Nakao Harumi、Kishimoto Yasushi、Hashimoto Kouichi、Kitamura Kazuo、Yamasaki Miwako、Nakao Kazuki、Watanabe Masahiko、Kano Masanobu、Kirino Yutaka、Aiba Atsu
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 7353-7353
  • DOI: 10.1038/s41598-019-43744-z
  • Peer Reviewed / Open Access
• [Journal Article] Localization of phospholipase C β3 in the major salivary glands of adult mice. (2019)
  • Author(s): Rawangwong A, Pidsaya A, Thoungseabyoun W, Tachow A, Sawatpanich T, Sakaew W, Yamasaki M, Watanabe M, Kondo H, Hipkaeo W.
  • Journal Title: Acta Histochem. Volume: 121 Issue: 4 Pages: 484-490
  • DOI: 10.1016/j.acthis.2019.04.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Heterogeneous localization of muscarinic cholinoceptor M1 in the salivary ducts of adult mice. (2019)
  • Author(s): Rawangwong A, Khrongyut S, Chomphoo S, Konno K, Yamasaki M, Watanabe M, Kondo H, Hipkaeo W.
  • Journal Title: Arch Oral Biol. Volume: 100 Pages: 14-22
  • DOI: 10.1016/j.archoralbio.2019.02.001
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Silent Learning. (2018)
  • Author(s): Rossato JI, Moreno A, Genzel L, Yamasaki M, Takeuchi T, Canals S, Morris RGM.
  • Journal Title: Curr Biol. Volume: 28 Issue: 21 Pages: 3508-3515
  • DOI: 10.1016/j.cub.2018.09.012
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Localization of nectin-2α at the boundary between the adjacent somata of the clustered cholinergic neurons and its regulatory role in the subcellular localization of the voltage-gated A-type K+ channel Kv4.2 in the medial habenula (2018)
  • Author(s): Shiotani Hajime、Miyata Muneaki、Itoh Yu、Wang Shujie、Kaito Aika、Mizoguchi Akira、Yamasaki Miwako、Watanabe Masahiko、Mandai Kenji、Mochizuki Hideki、Takai Yoshimi
  • Journal Title: J Comp Neurol. Volume: 526 Issue: 9 Pages: 1527-1549
  • DOI: 10.1002/cne.24425
  • NAID: 120006892079
  • Peer Reviewed
• [Journal Article] Olig2-Lineage Astrocytes: A Distinct Subtype of Astrocytes That Differs from GFAP Astrocytes (2018)
  • Author(s): Tatsumi Kouko、Isonishi Ayami、Yamasaki Miwako、Kawabe Yoshie、Morita-Takemura Shoko、Nakahara Kazuki、Terada Yuki、Shinjo Takeaki、Okuda Hiroaki、Tanaka Tatsuhide、Wanaka Akio
  • Journal Title: Front. Neuroanat. Volume: 12 Pages: 1-17
  • DOI: 10.3389/fnana.2018.00008
  • Peer Reviewed / Open Access
• [Journal Article] Locus Coeruleus and Dopamine-Dependent Memory Consolidation (2017)
  • Author(s): Yamasaki Miwako、Takeuchi Tomonori
  • Journal Title: Neural Plast. Volume: 2017 Pages: 1-15
  • DOI: 10.1155/2017/8602690
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Localization of photoperiod responsive circadian oscillators in the mouse suprachiasmatic nucleus (2017)
  • Author(s): Yoshikawa Tomoko、Inagaki Natsuko F.、Takagi Seiji、Kuroda Shigeru、Yamasaki Miwako、Watanabe Masahiko、Honma Sato、Honma Ken-ichi
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 820-820
  • DOI: 10.1038/s41598-017-08186-5
  • NAID: 120006360085
  • Peer Reviewed / Open Access
• [Journal Article] Glutamate transporter GLAST controls synaptic wrapping by Bergmann glia and ensures proper wiring of Purkinje cells. (2017)
  • Author(s): Miyazaki T, Yamasaki M, Hashimoto K, Kohda K, Yuzaki M, Shimamoto K, Tanaka K, Kano M, Watanabe M.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 114(28) Issue: 28 Pages: 7438-7443
  • DOI: 10.1073/pnas.1617330114
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Distinct central synapse that shows unique property to maintain AMPAR numbers equal (2018)
  • Author(s): Miwako Yamasaki
  • Organizer: Gordon Research Conference
  • Int'l Joint Research
• [Presentation] マウス線条体シナプスのAMPA受容体密度は細胞種や出入力経路によらず一様である (2017)
  • Author(s): 山崎美和子
  • Organizer: 第63回東北・北海道連合支部学術集会（弘前大学、青森県・弘前市）
• [Presentation] AMPAR density is homogeneous across striatal synapses irrespective of cell types and input pathways (2017)
  • Author(s): Miwako Yamasaki, Xiaohong Song, Masahiko Watanabe
  • Organizer: 第40回日本神経科学大会（幕張メッセ、千葉県・千葉市）