2014 Fiscal Year Annual Research Report
高次脳領域におけるシナプス伝達制御機構の分子形態学的研究
Project/Area Number |
24220007
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Research Institution | Hokkaido University |
Principal Investigator |
渡辺 雅彦 北海道大学, 医学(系)研究科(研究院), 教授 (70210945)
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Co-Investigator(Kenkyū-buntansha) |
崎村 建司 新潟大学, 脳研究所, 教授 (40162325)
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Project Period (FY) |
2012-05-31 – 2017-03-31
|
Keywords | シナプス / 情報伝達 / AMPA受容体 / 海馬 / 線条体 |
Outline of Annual Research Achievements |
平成26年度における研究実施により、以下の成果が得られた。 海馬シナプスにおけるAMPAR発現には、顕著な入力選択性と標的選択性が存在する。この選択的発現にはTARPg-2の選択的発現が関与し、その分子のノックアウトにより入力選択性と標的選択性が失われた。対照的に、TARPg-8のシナプス発現には選択性が乏しく、そのノックアウトにより海馬シナプスの基盤的AMPAR発現が低下した。 線条体の主要なニューロンである中型有棘細胞は、皮質由来のVGluT1陽性シナプスと視床由来のVGluT2陽性シナプスを形成する。この両者のシナプスにおけるAMPARの入力選択性は無いため、その原因を追求した。その結果、海馬とは異なり、線条体ではARPg-2発現の入力選択性はないことが判明した。 黒質のドーパミン投射線維は線条体中型有棘細胞に対して対称性シナプスを形成することが知られている。このシナプス伝達に関わる分子の発現を追求した所、シナプス前部はドーパミンの合成と放出・再取り込みに関わるドーパミン作動性を有するのに対して、シナプス後部はGABA作動性でGABAの伝達のGABAシナプスの接着分子を発現していた。この接着分子のノックダウンによりドーパミンシナプスは有意に減少した。一方、ドーパミン受容体は中型有棘細胞のシナプス外領域に広く発現していた。よって、ドーパミン投射線維はGABA作動性シナプスの接着分子を利用して係留接着を行ない、これを起点としてボリューム伝達に標的選択性を与えていることが考えられた。 扁桃体基底核には、内在性カンナビノイド伝達分子が高密度に集積し、陥入型シナプスを形成している。今回、VGluT3を発現するCCK陽性バスケット細胞がこのシナプスを選択的に形成することを明らかにした。
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Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
当初の研究計画の項目それぞれについて、着実にデータを集積し、一部は論文投稿の段階に達しているため。
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Strategy for Future Research Activity |
当初予定した研究計画を着実に実行し推進する。
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[Journal Article] Chemical corrector treatment ameliorates increased seizure susceptibility in a mouse model of familial temporal lobe epilepsy.2015
Author(s)
Yokoi N, Fukata Y, Kase D, Miyazaki T, Jaegle M, Ohkawa T, Takahashi N, Iwanari H, Mochizuki Y, Hamakubo T, Imoto K, Meijer D, Watanabe M, Fukata M
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Journal Title
Nat Med,
Volume: 21
Pages: 19-26
DOI
Peer Reviewed
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[Journal Article] Distinct subsynaptic localization of type 1 metabotropic glutamate (mGlu1) receptors at glutamatergic and GABAergic synapses in the rodent cerebellar cortex.2015
Author(s)
Mansouri M, Kasugai Y, Fukazawa Y, Bertaso F, Raynaud F, Perroy J, Fagni L, Kaufmann WA, Watanabe M, Shigemoto R, Ferraguti F
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Journal Title
Eur J Neurosci,
Volume: 41
Pages: 157-167
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Cell type-specific STORM superresolution imaging reveals nanoscale organization of cannabinoid signaling at hippocampal GABAergic synapses.2015
Author(s)
Dudok , Barn L, Ledri M, Szabó SI, Szabadits E, Pintér B, Woodhams SG, Henstridge CM, Balla GY, Nyilas R, Vargav C, Lee S, Matolcsi M, Cervenak J, Kacskovics I, Watanabe M, Sagheddu C, Melis M, Pistis M, Soltesz I, Katona I
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Journal Title
Nat Neurosci,
Volume: 18
Pages: 75-86
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Short-chain fatty acid sensing in rat duodenum.2015
Author(s)
Akiba Y, Inoue T, Kaji I, Higashiyama M, Iwamoto K, Watanabe M, Guth PH, Engel E, Kuwahara A, Kaunitz JD
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Journal Title
J Physiol,
Volume: 593
Pages: 585-599
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Untangling dopamine-adenosine receptor assembly in experimental parkinsonism.2015
Author(s)
Fernández-Dueñas V, Taura JJ, Cottet M, Gómez-Soler M, López-Cano M, Ledent C, Watanabe M, Trinquet E, Pin JP, Luján R, Durroux T, Ciruela F
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Journal Title
Dis Model Mech,
Volume: 8
Pages: 57-63
DOI
Peer Reviewed / Int'l Joint Research
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[Journal Article] Anterograde C1ql1 signaling is required in order to determine and maintain a single-winner climbing fiber in the mouse cerebellum.2015
Author(s)
Kakegawa W, Mitakidis N, Miura E, Abe M, Matsuda K, Takeo YH, Kohda K, Motohashi J, Takahashi A, Nagao S, Muramatsu S, Watanabe M, Sakimura K, Aricescu AR, Yuzaki M
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Journal Title
Neuron
Volume: 85
Pages: 316-329
DOI
Peer Reviewed
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[Journal Article] Inhibitory interneurons that express GFP in the PrP-GFP mouse spinal cord are morphologically heterogeneous, innervated by several classes of primary afferent and include lamina I projection neurons among their postsynaptic targets.2015
Author(s)
Ganley R, Iwagaki N, del Rio P, Baseer N, Dickie AC, Polgár E, Watanabe M, Abraira VE, Ginty DD, Riddell J, Todd AJ
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Journal Title
J Neurosci
Volume: in press
Pages: in press
Peer Reviewed
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[Journal Article] The synaptic targeting of mGluR1 by its carboxyl-terminal domain is crucial for cerebellar function.2014
Author(s)
Ohtani Y, Miyata M, Hashimoto K, Tabata T, Kishimoto Y, Fukaya M, Kase D, Kassai H, Nakao K, Hirata T, Watanabe M, Kano M, Aiba A
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Journal Title
J Neurosci,
Volume: 34
Pages: 2702-2712
DOI
Peer Reviewed
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[Journal Article] Dynorphin acts as a neuromodulator to inhibit itch in the dorsal horn of the spinal cord.2014
Author(s)
Kardon A, Polgár E, Hachisuka J, Cameron D, Savage S, McClement L, Cai X, Karnup S, Fan C, Hemenway G, Bernard C, Schwartz ES, Nagase H, Watanabe M, Furuta T, Kaneko T, Todd AJ, Ross SE
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Journal Title
Neuron
Volume: 82
Pages: 573-586
DOI
Peer Reviewed
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[Journal Article] Neuronal calcium binding proteins 1/2 localize to dorsal root ganglia and excitatory spinal neurons and are regulated by nerve injury.2014
Author(s)
Zhang M, Tortoriello G, Hsueh B, Tomer R, Ye L, Mitsios N, Borgius L, Kiehn O, Watanabe M, Uhlén M, Mulder J, Deisseroth K, Harkany T, Hökfelt T
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Journal Title
Proc. Natl. Acad. Sci. USA.
Volume: 111
Pages: E1149-1158
DOI
Peer Reviewed
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[Journal Article] Localization of serine racemase and its role in the skin.2014
Author(s)
Inoue R, Yoshihisa Y, Tojo Y, Okamura C, Yashida Y, Kishimoto J, Luan X, Watanabe M, Mizuguchi M, Nabeshima Y, Hamase K, Matsunaga K, Shimizu T, Mori H
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Journal Title
J Invest Dermatol
Volume: 134
Pages: 1618-1624, 2014
DOI
Peer Reviewed
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[Journal Article] Opposing role of NMDA receptor GluN2B and GluN2D in somatosensory development and maturation.2014
Author(s)
Yamasaki M, Okada R, Takasaki C, Toki S, Fukaya M, Natsume R, Sakimura K, Mishina M, Shirakawa T, Watanabe M
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Journal Title
J Neurosci,
Volume: 34
Pages: 11534-11548
DOI
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Co-assembly and coupling of SK2 channels and mGlu5 receptors.2014
Author(s)
Garcia-Negrego G, Soto D, Llorente J, Morató X, Galenkamp K, Gómez-Soler M, Fernández-Dueñas V, Watanabe M, Adelman J, Shigemoto R, Fukozawa Y, Luján R, Ciruela F
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Journal Title
J Neurosci,
Volume: 34
Pages: 14793-14802
DOI
Peer Reviewed
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[Journal Article] The glutamate receptor GluN2 subunit regulates synaptic trafficking of AMPA receptors in the neonatal mouse brain.2014
Author(s)
Hamada S, Ogawa I, Yamasaki M, Kiyama Y, Kassai H, Watabe AM, Nakao K, Aiba A, Watanabe M, Manabe T
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Journal Title
Eur J Neurosci,
Volume: 40
Pages: 3136-3146
DOI
Peer Reviewed
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[Journal Article] A new mouse allele of glutamate receptor delta 2 with cerebellar atrophy and progressive ataxia.2014
Author(s)
Miyoshi Y, Yoshioka Y, Suzuki K, Miyazaki T, Koura M, Saigoh K, Kajimura K, Monobe Y, Kusunok S, Matsuda J, Watanabe M, Hayasaka N
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Journal Title
PLoS ONE
Volume: 9
Pages: e107867-e107867
DOI
Peer Reviewed
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[Journal Article] Cerebellar Plasticity and Motor Learning Deficits in a Copy Number Variation Mouse Model of Autism.2014
Author(s)
Piochon C, Kloth A, Grasselli G, Titley H, Nakayama H, Hashimoto K, Wan V, Simmons D, Eissa T, Nakatani J, ACherskov A, Miyazaki T, Watanabe M, Takumi T, Kano M, Wang S, Hansel C
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Journal Title
Nat Commun
Volume: 5
Pages: 558-558
DOI
Peer Reviewed
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[Journal Article] Rab11a is required for apical protein localisation in the intestine.2014
Author(s)
Sobajima T, Yoshimura S, Iwano T, Kunii M, Watanabe M, Atik N, Mushiake S, Morii E, Koyama Y, Miyoshi E, Harada A
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Journal Title
Biol Open
Volume: 4
Pages: 86-94
DOI
Peer Reviewed
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