精神神経疾患を理解するシナプスのスクラップ＆ビルド

• Project Area: Dynamic regulation of brain function by Scrap & Build system
• Project/Area Number: 16H06463
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: 内匠 透 国立研究開発法人理化学研究所, 脳神経科学研究センター, チームリーダー (00222092)
• Co-Investigator(Kenkyū-buntansha): 萬代 研二 北里大学, 医学部, 教授 (50322186)
• Project Period (FY): 2016-06-30 – 2021-03-31
• Project Status: Granted (Fiscal Year 2019)
• Budget Amount: ¥99,190,000 (Direct Cost: ¥76,300,000、Indirect Cost: ¥22,890,000); Fiscal Year 2019: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2018: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2017: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2016: ¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000)
• Keywords: シナプス / スパイン / モデルマウス

Outline of Annual Research Achievements

興奮性シナプスは、神経細胞樹状突起から突き出たサブミクロンの突起（スパイン）上に形成される。スパインの数は形成（ビルド）と破壊（スクラップ）の動的平衡によって決まり、発達期に増加し成長後にゆるやかに減少することが知られているがその分子基盤は未解明である。申請者らは自閉スペクトラム症（ASD）モデルマウスに共通する所見として大脳皮質の錐体細胞でのスパイン形成と破壊が共に亢進することを見出した。本研究では、自閉症原因遺伝子とその下流に焦点を当て、大脳皮質でのスクラップ＆ビルド機構の分子機序を明らかにし、行動解析やin vivoスパインイメージング法によってスクラップ＆ビルド現象の破綻と高次機能障害との関係を解明する。
自閉症モデルマウス（patDp/+）のスパイン動態の変容(大脳皮質の錐体細胞でのスパイン形成と破壊が共に亢進すること)に関わる分子として、２光子顕微鏡を用いたスパインのin vivoイメージング法を用いて、ヒト１５番染色体（15q11-13）父性重複領域に存在するNdnを同定した。patDp/+マウスのシナプトソームを用いたプロテオミクス解析の結果、タンパク合成に関わる分子が同定され、局所翻訳とスパイン動態のリンクが示唆された。また、ミトコンドリア機能との関連が示唆された。
分担研究者の萬代は、細胞膜裏打ち分子のアファディンのスプライスバリアントのうち、l-アファディンがシナプスの接着装置のプンクタアドへレンシアジャンクションの形成をα-カテニンを介して制御していることを解明した。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

スパイン動態のin vivoイメージングと分子機構の解明：patDp/+マウスのスパイン動態の変容に関わる分子としてNdnを同定した。patDp/+マウスのシナプトソームを用いたプロテオミクス解析を行った。
シナプス・細胞接着に関連する分子の機能解析：自閉症関連遺伝子のうち、細胞接着によってシナプス形成に関わる分子として、Neuroligin1、アファディン、リンクス等に焦点を当て、それぞれの分子群のスパイン動態を中心に、野生型および自閉症患者でみられる変異型間の比較検討を行った。分担研究者の萬代は、アファディンによるシナプスの形成の分子機構の解明に取り組み、前シナプスの形成には接着分子のNGL-3が関与していること、後シナプスの形成にはPSD-95結合分子のMAGUINが関与していることを解明している。また、シナプスの維持にかかわる可能性のある分子を探索するためプロテオミクス解析を行い、その分子のリストを得ている。
発達期におけるシナプス後肥厚のリモデリング：生後発達期におけるマウスの脳のシナプス後肥厚（postsynaptic density, PSD）を調べ、そのタンパク質組成がどのように変化していくかを解析した。2、3、6、および12週齢のマウスの脳よりPSDを生化学的に精製し、質量分析による解析を行った。タンパク質の検出およびラベルフリー定量を行ったところ、2214タンパク質が全てのサンプルで検出・定量された。発達に伴って顕著な増加または減少を示したPSDタンパク質群の中には、シナプスの成熟や形成・除去に関わるとされる分子が多数見出された。よって、PSDにおけるこれらのタンパク質の増減は発達期のシナプスの数や形態の変化に寄与しているものと考えられる。また、今回得られたプロテオームのデータとトランスクリプトームのデータの相関を解析したところ、発達期におけるPSDタンパク質の量の変化は主に転写レベルで制御されていることが示唆された。

Strategy for Future Research Activity

スパイン動態のin vivoイメージングと分子機構の解明：in vivoイマージングを指標として、patDp/+マウスのスパイン動態の変容に関わる分子としてNdnを同定した。Ndnのスパインでの機能解析を継続する。
シナプス・細胞接着に関連する分子の機能解析：細胞接着によってシナプス形成に関わる分子として、Neuroligin1、アファディン、リンクス等に焦点を当て、それぞれの分子群のスパインとシナプス形成における生理学的機能について明らかにする。さらに、自閉症の発症と病態の進展における関わりについても検討する。分担研究者の萬代は、後シナプスの形成におけるアファディンとMAGUINの機能と作用機構について分子レベルから個体レベルの研究を推進する。また、プロテオミクス解析によって見出された分子について、シナプスにおける機能を解明する。
スクラップ＆ビルド現象の高次機能の評価：スクラップ&ビルド現象の個体レベルでの高次機能及び病態的意義に関する評価を行うために、覚醒下マウスのfMRIイメージング系を確立する。

Research Products

• [Int'l Joint Research] ペンシルバニア大学(米国)
• [Journal Article] UBE3A regulates the transcription of IRF, an anti-viral immunity (2019)
  • Author(s): Furumai R, Tamada K, Liu X, Takumi T
  • Journal Title: Hum Mol Genet Volume: in press
  • DOI: 10.1093/hmg/ddz019
  • Peer Reviewed
• [Journal Article] Fetal neural stem cells from a mouse model of 15q11-13 duplication syndrome exhibit altered differentiation into neurons and astrocytes (2019)
  • Author(s): Choi Y, Kim H, Choi M, Yang EJ, Takumi T, Kim HS
  • Journal Title: J Pharmacol Sci Volume: 139 Pages: 249-253
  • DOI: 10.1016/j.jphs.2018.12.007
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Interaction of nectin-2α with the auxiliary protein of the voltage-gated A-type K+ channel Kv4.2 dipeptidyl aminopeptidase-like protein at the boundary between the adjacent somata of clustered cholinergic neurons in the medial habenula (2019)
  • Author(s): Shiotani H, Miyata M, Mizutani K, Wang S, Mizoguchi A, Mochizuki H, *Mandai K, *Takai Y
  • Journal Title: Molecular and Cellular Neuroscience Volume: 94 Pages: 32-40
  • DOI: 10.1016/j.mcn.2018.11.001
  • Peer Reviewed
• [Journal Article] Glutamate and GABA in autism spectrum disorder-a translational magnetic resonance spectroscopy study in man and rodent models (2018)
  • Author(s): Horder J, Petrinovic MM, Mendez MA, Bruns A, Takumi T, Spooren W, Barker GJ, Kunnecke B, Murphy DG
  • Journal Title: Transl Psychiatry Volume: 8 Pages: 106-106
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Postsynaptic density proteins and their involvement in neurodevelopmental disorders (2018)
  • Author(s): Takeshi Kaizuka, Toru Takumi
  • Journal Title: J Biochem Volume: in press Pages: 447-455
  • DOI: 10.1093/jb/mvy022
  • Peer Reviewed
• [Journal Article] Common defects of spine dynamics and circuit function in neurodevelopment disorders: a systematic review of findings from in vivo optical imaging of mouse models (2018)
  • Author(s): Nakai N, Takumi T, Nakai J, Sato M
  • Journal Title: Frontiers in Neuroscience Volume: 12 Pages: 412-412
  • DOI: 10.3389/fnins.2018.00412
  • Peer Reviewed / Open Access
• [Journal Article] Identification of genes regulating GABAergic interneuron maturation. (2018)
  • Author(s): Fukumoto Keita、Tamada Kota、Toya Tsuyoshi、Nishino Tasuku、Yanagawa Yuchio、Takumi Toru
  • Journal Title: Neurosci Res Volume: in press Pages: 18-29
  • DOI: 10.1016/j.neures.2017.11.010
  • Peer Reviewed
• [Journal Article] Critical roles of serotonin-oxytocin interaction during the neonatal period in social behavior in 15q dup mice with autistic traits (2018)
  • Author(s): Nagano Masatoshi、Takumi Toru、Suzuki Hidenori
  • Journal Title: Sci Rep Volume: 8 Pages: 13675-13675
  • DOI: 10.1038/s41598-018-32042-9
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of l-afadin, but not s-afadin, in the formation of puncta adherentia junctions of hippocampal synapses. (2018)
  • Author(s): Maruo T, Sakakibara S, Miyata M, Itoh Y, Kurita S, Mandai K, Sasaki T, *Takai Y
  • Journal Title: Mol. Cell. Neurosci. Volume: 92 Pages: 40-49
  • DOI: 10.1016/j.mcn.2018.06.006
  • Peer Reviewed
• [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 Pages: 1527-1549
  • DOI: 10.1002/cne.24425
  • Peer Reviewed
• [Journal Article] The choroid plexus is an important circadian clock component. (2018)
  • Author(s): Myung Jihwan、Schmal Christoph、Hong Sungho、Tsukizawa Yoshiaki、Rose Pia、Zhang Yong、Holtzman Michael J.、De Schutter Erik、Herzel Hanspeter、Bordyugov Grigory、Takumi Toru
  • Journal Title: Nat Commun Volume: 9 Pages: 1062-1062
  • DOI: 10.1038/s41467-018-03507-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Id2 determines intestinal identity through repression of the foregut transcription factor, Irx5. (2018)
  • Author(s): Mori, K, Nakamura, H, Kurooka, H, Miyachi, H, Tamada, K, Sugai, M,Takumi, T, Yokota, Y
  • Journal Title: Mol Cell Biol Volume: 38
  • DOI: 10.1128/mcb.00250-17
  • Peer Reviewed / Open Access
• [Journal Article] A novel role of the antitumor agent tricyclodecan-9-yl-xanthogenate as an open channel blocker of KCNQ1/KCNE1. (2018)
  • Author(s): Wu, MK, Takemoto M, Luo H, Xu JJ, Lu MH, Kameyama M, Takumi T, Song WJ
  • Journal Title: European Journal of Pharmacology Volume: 824 Pages: 99-107
  • DOI: 10.1016/j.ejphar.2018.02.013
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CNV biology in neurodevelopmental disorders. (2018)
  • Author(s): Takumi Toru、Tamada Kota
  • Journal Title: Curr Opin Neurobiol Volume: 48 Pages: 183-192
  • DOI: 10.1016/j.conb.2017.12.004
  • Peer Reviewed / Open Access
• [Journal Article] Skeletal Site-specific Changes in Bone Mass in a Genetic Mouse Model for Human 15q11-13 Duplication Seen in Autism. (2017)
  • Author(s): Lewis KE, Sharan K, Takumi T, Yadav VK
  • Journal Title: Sci Rep Volume: 7 Pages: 9902-9902
  • DOI: 10.1038/s41598-017-09921-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Functional significance of rare neuroligin 1 variants found in autism. (2017)
  • Author(s): Nakanishi Moe、Nomura Jun、Ji Xiao、Tamada Kota、Arai Takashi、Takahashi Eiki、Bu?an Maja、Takumi Toru
  • Journal Title: PLoS Genet Volume: 13
  • DOI: 10.1371/journal.pgen.1006940
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV mice. (2017)
  • Author(s): Nakai N, Nagano M, Saitow F, Watanabe Y, Kawamura Y, Kawamoto A, Tamada K, Mizuma H, Onoe H, Watanabe Y, Monai H, Hirase H, Nakatani J, Inagaki H, Kawada T, Miyazaki T, Watanabe M, Sato Y, Okabe S, Kitamura K, Kano M, Hashimoto K, Suzuki H, Takumi T
  • Journal Title: Sci Adv Volume: 3(6)
  • DOI: 10.1126/sciadv.1603001
  • Peer Reviewed / Open Access
• [Journal Article] Potential contribution of tandem circadian enhancers to nonlinear oscillations in clock gene expression. (2017)
  • Author(s): Isao T. Tokuda, Akihiko Okamoto, Ritsuko Matsumura, Toru Takumi, Makoto Akashi
  • Journal Title: Mol Biol Cell Volume: 28 Pages: 2333-2342
  • DOI: 10.1091/mbc.e17-02-0129
  • Peer Reviewed / Open Access
• [Journal Article] Unusual semi-extractability as a hallmark of nuclear body-associated architectural noncoding RNAs (2017)
  • Author(s): Chujo T, Yamazaki T, Kawaguchi T, Kurosaka S, Takumi T, Nakagawa S, Hirose T
  • Journal Title: EMBO J Volume: - Pages: 1447-1462
  • DOI: 10.15252/embj.201695848
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Behavioral and neuroanatomical analyses in a genetic mouse model of 2q13 duplication. (2017)
  • Author(s): Kishimoto Keiko、Nomura Jun、Ellegood Jacob、Fukumoto Keita、Lerch Jason P.、Moreno-De-Luca Daniel、Bourgeron Thomas、Tamada Kota、Takumi Toru
  • Journal Title: Genes Cells Volume: 22 Pages: 436-451
  • DOI: 10.1111/gtc.12487
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Rodent models of genetic and chromosomal variations in psychiatric disorders. (2017)
  • Author(s): Nomura J, Kannan G, Takumi T
  • Journal Title: Psychiatry Clin Neurosci Volume: 71 Pages: 508-517
  • DOI: 10.1111/pcn.12524
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Distinct Defects in Spine Formation or Pruning in Two Gene Duplication Mouse Models of Autism. (2017)
  • Author(s): Wang M, Li H, Takumi T, Qiu Z, Xu X, Yu X, Bian WJ
  • Journal Title: Neurosci Bull Volume: 33 Pages: 143-152
  • DOI: 10.1007/s12264-017-0111-8
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] NGL-3-induced presynaptic differentiation of hippocampal neurons in an afadin-dependent, nectin-1-independent manner. (2017)
  • Author(s): Maruo Tomohiko、Mandai Kenji、Miyata Muneaki、Sakakibara Shotaro、Wang Shujie、Sai Kousyoku、Itoh Yu、Kaito Aika、Fujiwara Takeshi、Mizoguchi Akira、Takai Yoshimi
  • Journal Title: Genes Cells Volume: 22 Pages: 742-755
  • DOI: 10.1111/gtc.12510
  • Peer Reviewed
• [Journal Article] Roles of afadin in functional differentiations of hippocampal mossy fiber synapse. (2017)
  • Author(s): Geng Xiaoqi、Maruo Tomohiko、Mandai Kenji、Supriyanto Irwan、Miyata Muneaki、Sakakibara Shotaro、Mizoguchi Akira、Takai Yoshimi、Mori Masahiro
  • Journal Title: Genes Cells Volume: 22 Pages: 715-722
  • DOI: 10.1111/gtc.12508
  • Peer Reviewed
• [Journal Article] Multiple roles of afadin in the ultrastructural morphogenesis of mouse hippocampal mossy fiber synapses (2017)
  • Author(s): Wang, S., Kaito, A., Fujiwara, T., Maruo, T., Itoh, Y., Miyata, M., Sakakibara, S., Miyazaki, N., Murata, K., Yamaguchi, Y., Haruta, T., Nishioka, H., Motojima, Y., Komura, M., Kimura, K., Mandai, K., Takai, Y. and Mizoguchi, A.
  • Journal Title: J Comp Neurol Volume: Vol.525 Pages: 2719-2734
  • DOI: 10.1002/cne.24238
  • Peer Reviewed
• [Journal Article] Aging-dependent expression of synapse-related proteins in the mouse brain (2017)
  • Author(s): Shiotani, H., Maruo, T., Sakakibara, S., Miyata, M., Mandai, K., Mochizuki, H., Takai, Y.
  • Journal Title: Genes Cells Volume: 印刷中 Pages: 472-484
  • DOI: 10.1111/gtc.12489
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] CHRONO integrates behavioral stress and epigenetic control of metabolism. (2017)
  • Author(s): Hatanaka F, Takumi T
  • Journal Title: Ann Med Volume: 49 Pages: 352-356
  • DOI: 10.1080/07853890.2016.1276301
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Network Dynamics Mediate Circadian Clock Plasticity (2017)
  • Author(s): Azzi A, Evans JA, Leise T, Myung J, Takumi T, Davidson AJ, Brown SA
  • Journal Title: Neuron Volume: 93 Pages: 441-450
  • DOI: 10.1016/j.neuron.2016.12.022
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness. (2017)
  • Author(s): Nishita, M., Park, S.-Y., Nishio, T., Kamizaki, K., Wang, Z., Tamada, K., Takumi, T., Hashimoto, R., Otani, H., Pazour, G.J., Hsu, V.W., and Minami, Y.
  • Journal Title: Sci Rep. Volume: 7 Pages: 1-1
  • DOI: 10.1038/s41598-016-0028-x
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Serotonin rebalances cortical tuning and behavior linked autism symptoms in 15q11-13 CNV mice. (2017)
  • Author(s): Nakai N, Nagano M, Saitow F, Watanabe Y, Kawamura Y, Kawamoto A, Tamada K, Mizuma H, Onoe H, Watanabe Y, Monai H, Hirase H, Nakatani J, Inagaki H, Kawada T, Miyazaki T, Watanabe M, Sato Y, Okabe S, Kitamura K, Kano M, Hashimoto K, Suzuki H, Takumi T
  • Journal Title: Sci Adv Volume: -
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Roles of afadin in the formation of the cellular architecture of the mouse hippocampus and dentate gyrus. (2017)
  • Author(s): Miyata M, Maruo T, Kaito A, Wang S, Yamamoto H, Fujiwara T, Mizoguchi A, Mandai K, Takai Y
  • Journal Title: Molecular and Cellular Neuroscience Volume: 79 Pages: 34-44
  • DOI: 10.1016/j.mcn.2016.12.007
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Structural, super-resolution microscopy analysis of paraspeckle nuclear body organization (2016)
  • Author(s): Wu M, Takemoto M, Taniguchi M, Takumi T, Okazaki T, Song WJ
  • Journal Title: Journal of Cell Biology Volume: 311 Pages: 817-830
  • DOI: 10.1083/jcb.201601071
  • NAID: 120005893291
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] CHD8 haploinsufficiency results in autistic-like phenotypes in mice. (2016)
  • Author(s): Katayama Y, Nishiyama M, Shoji H, Ohkawa Y, Kawamura A, Sato T, Suyama M, Takumi T, Miyakawa T, Nakayama KI.
  • Journal Title: Nature Volume: 537 Issue: 7622 Pages: 28636-28636
  • DOI: 10.1038/nature19357
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Exome sequencing in the knockin mice generated using the CRISPR/Cas system (2016)
  • Author(s): Nakajima K, Kazuno AA, Kelsoe J, Nakanishi M, Takumi T, Kato T
  • Journal Title: Scientific Reports Volume: 6 Pages: 34703-34703
  • DOI: 10.1038/srep34703
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] FUS/TLS acts as an aggregation-dependent modifier of polyglutamine disease model mice. (2016)
  • Author(s): Kino Y, Washizu C, Kurosawa M, Yamada M, Doi H, Takumi T, Adachi H, Katsuno M, Sobue G, Hicks GG, Hattori N, Shimogori T, Nukina N.
  • Journal Title: Scientific Reports Volume: 6 Pages: 35236-35236
  • DOI: 10.1038/srep35236
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Localization of nectin-2delta at perivascular astrocytic endfoot processes and degeneration of astrocytes and neurons in nectin-2 knockout mouse brain. (2016)
  • Author(s): Miyata M, Mandai K, Maruo T, Sato J, Shiotani H, Kaito A, Itoh Y, Wang S, Fujiwara T, Mizoguchi A, Takai Y, Rikitake Y
  • Journal Title: Brain Research Volume: 1649 Pages: 90-101
  • DOI: 10.1016/j.brainres.2016.08.023
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Serotonin, Serine and synapse in autism (2018)
  • Author(s): Toru Takumi
  • Organizer: 2018 Spring International Convention of The Pharmaceutical Society of Korea
  • Int'l Joint Research / Invited
• [Presentation] Copy number variation model of autism (2018)
  • Author(s): Toru Takumi
  • Organizer: Cold Spring Harbor Asia Conferences
  • Int'l Joint Research / Invited
• [Presentation] Modeling Autism (2018)
  • Author(s): Toru Takumi
  • Organizer: KIST Autism Symposium
  • Int'l Joint Research / Invited
• [Presentation] Necdin regulates spine dynamics in 15q duplication mode mice (2017)
  • Author(s): 戸谷豪、福本景太、玉田紘太、田中慎二、三澤日出巳、岡部繁男、内匠透
  • Organizer: 第１２２回日本解剖学会全国学術集会
  • Place of Presentation: 長崎大学、長崎
  • Year and Date: 2017-03-28
  • Invited
• [Presentation] Abnormal synapse dynamics in mouse models for autism spectrum disorders (2017)
  • Author(s): Shinji Tanaka, Masaaki Isshiki, Risa Iguchi, Shinji Urata, Shunsuke Mizutani, Toshihiko Kuriu, Katsuhiko Tabuchi, Toru Takumi, Shigeo Okabe
  • Organizer: 第１２２回日本解剖学会全国学術集会
  • Place of Presentation: 長崎大学、長崎
  • Year and Date: 2017-03-28
  • Invited
• [Presentation] 自閉症責任領域15q11-q13モデルマウスにおける原因遺伝子の探索 (2017)
  • Author(s): 玉田絋太、福本景太、戸谷豪志、Sandra Ruf, Francois Spitz, 内匠透
  • Organizer: 2017年度生命化学系学会合同年次大会、第４０回日本分子生物学会年会、第９０回日本生化学会大会
  • Invited
• [Presentation] Awake mouse functional MRI for the detection of the abnormal neural circuit in autism model mouse (2017)
  • Author(s): Tomokazu Tsurugizawa, Kota Tamada, Akihiko Kitamura, Nobukazu Ono, S. Karakawa, Y. Kodama, Toru Takumi
  • Organizer: Neuroscience 2017
  • Int'l Joint Research / Invited
• [Presentation] 新規NLGN1自閉症変異とヒト型モデルマウス (2017)
  • Author(s): 内匠透
  • Organizer: 合同年会2017 Sapporo：第３９回日本生物学的精神医学会、第４７回日本神経精神薬理学会
  • Invited
• [Presentation] Brain structural and behavioral abnormalities in a mouse model for 15q25.2-25.3 microdeletion syndrome (2017)
  • Author(s): Jun Nomura, Akifumi Kanda, Jacob Ellegood, Jason P Lerch, Yusuke Sotomaru, Toru Takumi
  • Organizer: 第６０回日本神経化学会大会 ２０１７年９月７－９日（仙台国際センター、仙台
  • Invited
• [Presentation] Takumi mouse model of dup15q (2017)
  • Author(s): Toru Takumi
  • Organizer: Dup15q Alliance 2017 Science Symposium
  • Int'l Joint Research / Invited
• [Presentation] Awake mouse functional MRI detects the dysfunction of the neural circuit in neuropsychiatric disorder mouse models (2017)
  • Author(s): Tomokazu Tsurugizawa, Kota Tamada, Nobukazu Ono, Akihiko Kitamura, Toru Takumi
  • Organizer: 第４０回日本神経科学大会
  • Invited
• [Presentation] Behavioral Neuroscience of Autism (2017)
  • Author(s): Toru Takumi
  • Organizer: IBNS(International Behavioral Neuroscience Society)2017 Annual Meeting
  • Int'l Joint Research / Invited
• [Presentation] Necdin promotes formation of dendritic spines in ASD model mice for 15q syndrome (2017)
  • Author(s): Tsuyoshi Toya, Keita Fukumoto, Nobuhiro Nakai, Shinji Tanaka, Shigeo Okabe, Peter Scheiffele, Hidemi Misawa, Kota Tamada, Toru Takumi
  • Organizer: 次世代脳プロジェクト冬のシンポジウム
• [Presentation] 自閉スペクトラム症のCNVに基づくモデル神経細胞のトランスクリプトーム解析 (2017)
  • Author(s): 六峰弘晃、Amila Zuko、河野掌、Jay Shin, Pierro Catninci, 三澤日出巳、野村淳、内匠透
  • Organizer: 2017年度生命化学系学会合同年次大会、第４０回日本分子生物学会年会。第９０回日本生化学会大会
• [Presentation] Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 duplication mice (2017)
  • Author(s): Nobuhiro Nakai, Masatoshi Nagano, Fumihito Saitow, Yasuhito Watanabe, Yoshinobu Kawamura, Hiroshi Mizuma, Hirotaka Onoue, Kota Tamada, Hiromu Monai, Hajime Hirase, Taisuke Miyazaki, Masahiko Watanabe, Shigeo Okabe, Masanobu Kano, Kouichi Hashimoto, Hidenori Suzuki, Toru Takumi
  • Organizer: Neuroscience 2017
  • Int'l Joint Research
• [Presentation] Serotonin intervention alleviates cortical response to sensory stimuli and social behavior in human 15q duplication model mice (2017)
  • Author(s): Nobuhiro Nakai, Masatoshi Nagano, Fumihito Saitow, Yasuhito Watanabe, Yoshinobu Kawamura, Hiroshi Mizuma, Hirotaka Onoue, Kota Tamada, Hiromu Monai, Hajime Hirase, Taisuke Miyazaki, Masahiko Watanabe, Shigeo Okabe, Masanobu Kano, Kouichi Hashimoto, Hidenori Suzuki, Toru Takumi
  • Organizer: Cell Symposia “Big Questions in Neuroscience”
  • Int'l Joint Research
• [Presentation] Identification and functional characterization of neuroligin1 variants in autism spectrum disorder (2017)
  • Author(s): Moe Nakanishi, Jun Nomura, Xiao Ji, Kota Taamada, Takashi Arai, Eiki Takahashi, Maja Bucan, Toru Takumi
  • Organizer: International Autism Conference Tokyo 2017
  • Int'l Joint Research
• [Presentation] Calcium Imaging of the Insular Cortex during the Social Interaction and Sensory Test: a Study with Miniaturized Fluorescence Microscope (2017)
  • Author(s): 三浦勇、九里 信夫、中井信裕、川俣貴一、内匠透
  • Organizer: 第７６回日本脳神経外科学会学術集会
• [Presentation] Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV (2017)
  • Author(s): Nobuhiro Nakai, Masatoshi Nagano, Fumihito Saitow, Yasuhito Watanabe, Yoshinobu Kawamura, Hiroshi Mizuma, Hirotaka Onoue, Kota Tamada, Hiromu Monai, Hajime Hirase, Taisuke Miyazaki, Masahiko Watanabe, Shigeo Okabe, Masanobu Kano, Kouichi Hashimoto, Hidenori Suzuki, Toru Takumi
  • Organizer: 第４０回日本神経科学大会
• [Presentation] Necdin regulates spine dynamics in 15q duplicated model mice (2017)
  • Author(s): Tsuyoshi Toya, Keita Fukumoto, Nobuhiro Nakai, Shinji Tanaka, Shigeo Okabe, Peter Scheiffele, Hidemi Misawa, Kota Tamada, Toru Takumi
  • Organizer: 第４０回日本神経科学大会
• [Presentation] Copy number variation models with autism (2016)
  • Author(s): Toru Takumi
  • Organizer: 14th Meeting of the Asian-Pacific Society for Neurochemistry
  • Place of Presentation: Kuala Lumpur, Malaysia
  • Year and Date: 2016-08-29
  • Int'l Joint Research / Invited
• [Presentation] Modeling autism (2016)
  • Author(s): Toru Takumi
  • Organizer: 第３９回日本神経科学大会
  • Place of Presentation: パシフィコ横浜、横浜
  • Year and Date: 2016-07-22
  • Invited
• [Presentation] Homozygotes of model mice for human chromosome 15q11-q13 duplication show severe developmental abnormalities. (2016)
  • Author(s): Jin Nakatani, Natsu Koyama, Seiji Hitoshi, Toru Takumi, Tomoko Kato, Ikuo Tooyama, Akihiko Shiino, Shigehiro Morikawa, Toshiro Inubushi
  • Organizer: 第３９回日本神経科学大会
  • Place of Presentation: パシフィコ横浜、横浜
  • Year and Date: 2016-07-20
• [Presentation] Neurobehavioral abnormalities in a mouse model for huma 15q25.2-25.3 deletion (2016)
  • Author(s): Jun Nomura, Akifumi Kanda, Yusuke Sotomaru, Toru Takumi
  • Organizer: 第３９回日本神経科学大会
  • Place of Presentation: パシフィコ横浜、横浜
  • Year and Date: 2016-07-20
• [Presentation] Dosage-dependent cognitive dysfunctions in a genetic mouse model of 2q13 (Nphp1) duplication (2016)
  • Author(s): Keiko Kishimoto, Jun Nomura, Kota Tamada, Thomas Bourgeron, Mereno Du Luca Daniel, Toru Takumi
  • Organizer: 第３９回日本神経科学大会
  • Place of Presentation: パシフィコ横浜、横浜
  • Year and Date: 2016-07-20
• [Presentation] Identification and functional characterization of a novel Neuroligin1 variant in autism spectrum disorder (2016)
  • Author(s): Moe Nakanishi, Jun Nomura, Xiaoxi Liu, Takashi Arai, Eiki Takahashi, Maja Bucan, Li Zhou, Manabu Abe, Kenji Sakimura, Toru Takumi
  • Organizer: 第３９回日本神経科学大会
  • Place of Presentation: パシフィコ横浜、横浜
  • Year and Date: 2016-07-20
• [Presentation] Phenotypic analysis of a mouse model for 15q25.2-25.3 deletion syndrome (2016)
  • Author(s): Jun Nomura, Akifumi Kanda, Yusuke Sotomaru, Toru Takumui
  • Organizer: 30th CINP World Congress of Neuropsychopharmacology
  • Place of Presentation: Seoul, South Korea
  • Year and Date: 2016-07-03
  • Int'l Joint Research
• [Presentation] A novel mutation associated autism in Neuroligin1 (2016)
  • Author(s): Moe Nakanishi, Takashi Arai, Maja Bucan, Xiao Ji, Xiaoxi Liu, Jun Nomura, Eiki Takahashi, Toru Takumi
  • Organizer: 30th CINP World Congress of Neuropsychopharmacology
  • Place of Presentation: Seoul, South Korea
  • Year and Date: 2016-07-03
  • Int'l Joint Research
• [Presentation] 自閉スペクトラム症の生物学的理解 (2016)
  • Author(s): 内匠透
  • Organizer: 第４６回日本神経精神薬理学会年会
  • Place of Presentation: Seoul, South Korea
  • Year and Date: 2016-07-02
  • Invited
• [Presentation] 発達障害と相関する新規CNV(15q25.2-25.3)動物モデルの開発 (2016)
  • Author(s): 野村淳、神田暁史、外丸祐介、内匠透
  • Organizer: 第４６回日本神経精神薬理学会年会
  • Place of Presentation: Seoul, South Korea
  • Year and Date: 2016-07-02
• [Presentation] Neuroligin1における自閉症関連変異の同定と機能解析 (2016)
  • Author(s): 仲西萌絵、野村淳、Xiaoxi Liu、Maja Bucan、高橋英機、阿部学、li Zhou、崎村健司、内匠透
  • Organizer: 第４６回日本神経精神薬理学会年会
  • Place of Presentation: Seoul, South Korea
  • Year and Date: 2016-07-02