Study of the molecular-anatomical basis common to neuromodulatory synapses

• Project/Area Number: 15K06732
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Hokkaido University
• Principal Investigator: Uchigashima Motokazu 北海道大学, 医学研究院, 助教 (10614662)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: アセチルコリン / ノルアドレナリン / ドーパミン / シナプス / 免疫組織化学 / 電子顕微鏡 / 神経修飾因子 / ドパミン / 線条体 / 分界条床核 / ニューロリギン / ニューレキシン / アセチルコリン受容体

Outline of Final Research Achievements

We examined by immunohistochemistry the molecular composition of synaptic structures which release neuromodulators including dopamine, acetylcholine, and noradrenaline in the brain. We revealed that these synapses were composed of non-GABAergic presynaptic structures and GABAergic postsynaptic membranes. This mismatch between presynaptic and postsynaptic structures at distinct neuromodulator synapses suggests GABAergic postsynaptic molecules commonly anchor the molecular machinery to release neuromodulators to target structures.

Research Products

• [Int'l Joint Research] マサチューセッツ州立大学医学部(米国)
• [Int'l Joint Research] マサチューセッツ州立大学医学部(米国)
• [Journal Article] Ventrolateral striatal medium spiny neurons positively regulate food-incentive, goal-directed behavior independently of D1 and D2 selectivity. (2017)
  • Author(s): Akiyo Natsubori, Iku Tsustui-Kimura, Hiroshi Nishida, Youcef Bouchekioua, Hiroshi Sekiya, Motokazu Uchigashima, Masahiko Watanabe, Alban de Kerchove d'Exaerde, Masaru Mimura, Norio Takata, and Kenji Tanaka
  • Journal Title: Journal of Neuroscience Volume: 37 Issue: 10 Pages: 2723-2733
  • DOI: 10.1523/jneurosci.3377-16.2017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dysfunction of ventrolateral striatal dopamine receptor type 2-expressing medium spiny neurons impairs instrumental motivation. (2017)
  • Author(s): Tsutsui-Kimura I, Takiue H, Yoshida K, Xu M, Yano R, Ohta H, Nishida H, Bouchekioua Y, Okano H, Uchigashima M, Watanabe M, Takata N, Drew MR, Sano H, Mimura M, Tanaka KF.
  • Journal Title: Nat Commun. Volume: 8 Issue: 1 Pages: 14304-14304
  • DOI: 10.1038/ncomms14304
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Using a novel PV-Cre rat model to characterize pallidonigral cells and their terminations. (2016)
  • Author(s): Oh Y-M, Karube F, Takahashi S, Kobayashi K, Takada M, Uchigashima M, Watanabe M, Nishizawa K, Kobayashi K, *Fujiyama F
  • Journal Title: Brain Struct Funct Volume: 印刷中 Issue: 5 Pages: 2359-2378
  • DOI: 10.1007/s00429-016-1346-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Metabotropic Glutamate Receptor Subtype 1 Mediates Experience-Dependent Maintenance of Mature Synaptic Connectivity in the Visual Thalamus (2016)
  • Author(s): Madoka Narushima, Motokazu Uchigashima, Yuki Yagasaki, Takeshi Harada, Yasuyuki Nagumo, Naofumi Uesaka, Kouichi Hashimoto, Atsu Aiba, Masahiko Watanabe, Mariko Miyata and Masanobu Kano
  • Journal Title: Neuron Volume: 91 Issue: 5 Pages: 1097-1109
  • DOI: 10.1016/j.neuron.2016.07.035
  • Peer Reviewed / Open Access
• [Journal Article] Crucial roles of the endocannabinoid 2-arachidonoylglycerol in the suppression of epileptic seizures. (2016)
  • Author(s): Sugaya Y, Yamazaki M, Uchigashima M, Kobayashi K, Watanabe M, Sakimura K, Kano M
  • Journal Title: Cell Rep Volume: 16 Issue: 5 Pages: 1405-15
  • DOI: 10.1016/j.celrep.2016.06.083
  • Peer Reviewed / Open Access
• [Journal Article] Trans-synaptic modulation of kainate receptor functions by C1q-like proteins. (2016)
  • Author(s): Matsuda K, Budisantoso T, Mitakidis N, Sugaya Y, Miura E, Kakegawa W, Yamasaki M, Konno K, Uchigashima M, Abe M, Watanabe I, Kano M, Watanabe M, Sakimura K, Aricescu AR, Yuzaki M.
  • Journal Title: Neuron Volume: in press Issue: 4 Pages: 752-767
  • DOI: 10.1016/j.neuron.2016.04.001
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Dopamine synapse is a neuroligin-2-mediated contact between dopaminergic presynaptic and GABAergic postsynaptic structures (2016)
  • Author(s): Uchigashima M, Ohtsuka T, Kobayashi K, Watanabe M
  • Journal Title: Proc Natl Acad Sci U S A Volume: 113 (15) Pages: 4206-11
  • NAID: 120005849913
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Territories of heterologous inputs onto Purkinje cell dendrites are segregated by mGluR1-dependent parallel fiber synapse elimination (2016)
  • Author(s): Ichikawa R, Hashimoto K, Miyazaki T, Uchigashima M, Yamasaki M, Aiba A, Kano M, Watanabe M
  • Journal Title: Proc Natl Acad Sci U S A Volume: 113 (8) Issue: 8 Pages: 2282-7
  • DOI: 10.1073/pnas.1511513113
  • NAID: 120005828473
  • Peer Reviewed / Open Access
• [Journal Article] Phosphoproteomics of the Dopamine Pathway Enables Discovery of Rap1 Activation as a Reward Signal In Vivo (2016)
  • Author(s): Nagai T, Nakamuta S, Kuroda K, Nakauchi S, Nishioka T, Takano T, Zhang X, Tsuboi D, Funahashi Y, Nakano T, Yoshimoto J, Kobayashi K, Uchigashima M, Watanabe M, Miura M, Nishi A, Kobayashi K, Yamada K, Amano M, Kaibuchi K
  • Journal Title: Neuron Volume: 89 (3) Issue: 3 Pages: 550-65
  • DOI: 10.1016/j.neuron.2015.12.019
  • Peer Reviewed / Open Access
• [Journal Article] Production of monoclonal antibodies against GPCR using cell-free synthesized GPCR antigen and biotinylated liposome-based interaction assay (2015)
  • Author(s): Takeda H, Ogasawara T, Ozawa T, Muraguchi A, Jih PJ, Morishita R, Uchigashima M, Watanabe M, Fujimoto T, Iwasaki T, Endo Y, Sawasaki T
  • Journal Title: Sci Rep Volume: 5 Issue: 1 Pages: 11333-11333
  • DOI: 10.1038/srep11333
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Striatal dopamine synapses are neuroligin-2-mediated heterologous contacts between dopaminergic presynapse and GABAergic postsynapse (2015)
  • Author(s): Motokazu Uchigashima, Masahiko Watanabe
  • Organizer: Neuroscience 2015
  • Place of Presentation: シカゴ(アメリカ)
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] 皮質系構造においてVGluT3/CCK発現バスケット細胞は内因性カンナビノイドシグナル伝達関連分子を豊富に備えた貫入型シナプスを形成する。 (2015)
  • Author(s): 内ヶ島基政、渡辺雅彦
  • Organizer: 第３８回日本神経科学大会
  • Place of Presentation: 神戸国際会議場（神戸）
  • Year and Date: 2015-07-28
• [Remarks] プレスリリース（北海道大学）
  • URL: http://www.hokudai.ac.jp/news/160329_med_pr.pdf
• [Remarks] プレスリリース(日本医療研究開発機構)
  • URL: http://www.amed.go.jp/news/release_20160329-02.html