マルチスケール精神病態の構成的理解（総括班）

• Project Area: Constructive understanding of multi-scale dynamism of neuropsychiatric disorders
• Project/Area Number: 18H05428
• 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 (2019-2022); Gunma University (2018)
• Principal Investigator: 高木 朗子 (林朗子 / 林 朗子 / 高木朗子) 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 (60415271)
• Co-Investigator(Kenkyū-buntansha): 澤田 誠 名古屋大学, 環境医学研究所, 教授 (10187297) ; 古屋敷 智之 神戸大学, 医学研究科, 教授 (20362478) ; 加藤 忠史 順天堂大学, 医学部, 教授 (30214381) ; 岩本 和也 熊本大学, 大学院生命科学研究部(医), 教授 (40342753) ; 那波 宏之 和歌山県立医科大学, 薬学部, 教授 (50183083) ; 喜田 聡 東京大学, 大学院農学生命科学研究科(農学部), 教授 (80301547) ; 林 康紀 京都大学, 医学研究科, 教授 (90466037) ; 吉川 武男 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 (30249958)
• Project Period (FY): 2018-06-29 – 2023-03-31
• Project Status: Granted (Fiscal Year 2022)
• Budget Amount: ¥271,310,000 (Direct Cost: ¥208,700,000、Indirect Cost: ¥62,610,000); Fiscal Year 2022: ¥38,220,000 (Direct Cost: ¥29,400,000、Indirect Cost: ¥8,820,000); Fiscal Year 2021: ¥33,670,000 (Direct Cost: ¥25,900,000、Indirect Cost: ¥7,770,000); Fiscal Year 2020: ¥39,390,000 (Direct Cost: ¥30,300,000、Indirect Cost: ¥9,090,000); Fiscal Year 2019: ¥37,440,000 (Direct Cost: ¥28,800,000、Indirect Cost: ¥8,640,000); Fiscal Year 2018: ¥122,590,000 (Direct Cost: ¥94,300,000、Indirect Cost: ¥28,290,000)
• Keywords: マルチスケール / マイクロ精神病態 / 構成的理解 / モデリング / トランスオミクス / 精神疾患 / 種間横断比較 / シミュレーション

Outline of Annual Research Achievements

FY2020はコロナ禍の中でも領域活動をなるべく高いレベルで維持し、領域が意義のあるバーチャル研究所として機能することに注力した。領域運営の企画調整は、2回/年の総括班会議をビデオ会議で開催した。協議事項は、領域会議や若手育成合宿などの運営方針、研究支援活動を促進するための方策、ニュースレター内容、公募研究採択方針など多岐にわたった。領域会議は、第3回をWEB開催（2020年7月3～4日）し、100名強の研究者の活発な議論が行われた。第2回若手育成セミナー（2020年12月16日）は、最先端技術に関する対話式ワークショップをWEB開催し、多くの若手研究者の参加があった。研究支援委員会では、技術や生物試料（iPS細胞、死後脳など）の供与などを介して、領域全体へ支援活動を行った。その結果、前年度に引き続き、領域内共同研究は順調に進行していると報告を受けている。有機的な人的交流も活発で、あるWET研究の計画班員の研究室で学位を取得した学生が、Dry研究をしている計画班員の研究室に博士研究員として異動するなど、領域のWET-DRY融合理念が草の根的に広がっている。ニュースレターは第4版を出版する予定で、若手研究者にむけた多くのコンテンツを予定しているとともに、領域の活動を広く周知するために工夫する。

Current Status of Research Progress

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

Reason

コロナ禍にもかかわらず、オンラインなどを利活用し、領域内連携の維持ができているため。

Strategy for Future Research Activity

第4回領域会議（2021年5月18日、Zoom）、第3回若手育成セミナー（2021年12月18日、Zoom）などの領域活動を例年と同じ規模で開催する。とりわけ、若手育成合宿は、基礎と臨床との融合に焦点を絞った本領域ならではの刺激的な対話性のワークショップを目指す。

Research Products

• [Journal Article] Optical interrogation of multi-scale neuronal plasticity underlying behavioral learning (2021)
  • Author(s): Tsutsumi Shinichiro、Hayashi-Takagi Akiko
  • Journal Title: Current Opinion in Neurobiology Volume: 67 Pages: 8-15
  • DOI: 10.1016/j.conb.2020.07.002
  • Peer Reviewed
• [Journal Article] CaMKII activation persistently segregates postsynaptic proteins via liquid phase separation (2021)
  • Author(s): Hosokawa Tomohisa、Liu Pin-Wu、Cai Qixu、Ferreira Joana S.、Levet Florian、Butler Corey、Sibarita Jean-Baptiste、Choquet Daniel、Groc Laurent、Hosy Eric、Zhang Mingjie、Hayashi Yasunori
  • Journal Title: Nature Neuroscience Volume: -
  • DOI: 10.1038/s41593-021-00843-3
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Resting-state dopaminergic cell firing in the ventral tegmental area negatively regulates affiliative social interactions in a developmental animal model of schizophrenia (2021)
  • Author(s): Sotoyama Hidekazu、Namba Hisaaki、Kobayashi Yutaro、Hasegawa Taku、Watanabe Dai、Nakatsukasa Ena、Sakimura Kenji、Furuyashiki Tomoyuki、Nawa Hiroyuki
  • Journal Title: Transl Psychiatry Volume: 11 Pages: 236-236
  • DOI: 10.1038/s41398-021-01346-2
  • Peer Reviewed / Open Access
• [Journal Article] Developmental excitation-inhibition imbalance underlying psychoses revealed by single-cell analyses of discordant twins-derived cerebral organoids (2020)
  • Author(s): Sawada Tomoyo、Chater Thomas E.、Sasagawa Yohei、Yoshimura Mika、Fujimori-Tonou Noriko、Tanaka Kaori、Benjamin Kynon J. M.、Paquola Apu C. M.、Erwin Jennifer A.、Goda Yukiko、Nikaido Itoshi、Kato Tadafumi
  • Journal Title: Molecular Psychiatry Volume: 25 Pages: 2695-2711
  • DOI: 10.1038/s41380-020-0844-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evidence for Altered Metabolism of Sphingosine-1-phosphate in the Corpus Callosum of Patients with Schizophrenia (2020)
  • Author(s): Esaki, K., Balan, S., Iwayama, Y., Shimamoto-Mitsuyama, C., Hirabayashi, Y., Dean, B. & Yoshikawa, T.
  • Journal Title: Schizophrenia Bulletin Volume: - Pages: 1172-1181
  • DOI: 10.1093/schbul/sbaa052
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Two functionally distinct serotonergic projections into hippocampus (2020)
  • Author(s): Luchetti Alessandro、Bota Ayaka、Weitemier Adam、Mizuta Kotaro、Sato Masaaki、Islam Tanvir、McHugh Thomas J.、Tashiro Ayumu、Hayashi Yasunori
  • Journal Title: The Journal of Neuroscience Volume: - Pages: 4936-4944
  • DOI: 10.1523/jneurosci.2724-19.2020
  • NAID: 120006893992
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Investigation of betaine as a novel psychotherapeutic for schizophrenia (2019)
  • Author(s): Ohnishi T, Balan S, Toyoshima M, Maekawa M, Ohba H, Watanabe A, Iwayama Y, Hisano Y, Nagaoka A, Hino M, Kunii Y, Kakita A, Yabe H, Yoshikawa T.
  • Journal Title: EBioMedicine Volume: 45 Pages: 432-446
  • DOI: 10.1016/j.ebiom.2019.05.062
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hippocampal clock regulates memory retrieval via Dopamine and PKA-induced GluA1 phosphorylation (2019)
  • Author(s): Hasegawa Shunsuke、Fukushima Hotaka、Hosoda Hiroshi、Serita Tatsurou、Ishikawa Rie、Rokukawa Tomohiro、Kawahara-Miki Ryouka、Zhang Yue、Ohta Miho、Okada Shintaro、Tanimizu Toshiyuki、Josselyn Sheena A.、Frankland Paul W.、Kida Satoshi
  • Journal Title: Nature Communications Volume: 10 Pages: 5766-5766
  • DOI: 10.1038/s41467-019-13554-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Reciprocal Activation within a Kinase-Effector Complex Underlying Persistence of Structural LTP. (2019)
  • Author(s): Saneyoshi T, Matsuno H, Suzuki A, Murakoshi H, Hedrick NG, Agnello E, O'Connell R, Stratton MM, Yasuda R, and Hayashi Y
  • Journal Title: Neuron Volume: 102 Pages: 11991210-11991210
  • DOI: 10.1016/j.neuron.2019.04.012
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Bayesian psychophysics model of sense of agency (2019)
  • Author(s): Legaspi Roberto、Toyoizumi Taro
  • Journal Title: Nature Communications Volume: 10 Pages: 4250-4250
  • DOI: 10.1038/s41467-019-12170-0
  • Peer Reviewed / Open Access
• [Journal Article] Roles of multiple lipid mediators in stress and depression (2019)
  • Author(s): Furuyashiki Tomoyuki、Akiyama Satoshi、Kitaoka Shiho
  • Journal Title: International Immunology Volume: 未定 Pages: 579-587
  • DOI: 10.1093/intimm/dxz023
  • Peer Reviewed / Open Access
• [Journal Article] Social defeat stress induces phosphorylation of extracellular signal-regulated kinase in the leptomeninges in mice (2019)
  • Author(s): Okamura Satoshi、Nagai Hirotaka、Numa Chisato、Nagai Midori、Shinohara Ryota、Furuyashiki Tomoyuki
  • Journal Title: Neuropsychopharmacology Reports Volume: -
  • DOI: 10.1002/npr2.12051
  • NAID: 120006713572
  • Peer Reviewed / Open Access
• [Journal Article] Iso-α-acids, the bitter components of beer, improve hippocampus-dependent memory through vagus nerve activation (2019)
  • Author(s): Ano Yasuhisa、Hoshi Ayaka、Ayabe Tatsuhiro、Ohya Rena、Uchida Shinichi、Yamada Koji、Kondo Keiji、Kitaoka Shiho、Furuyashiki Tomoyuki
  • Journal Title: The FASEB Journal Volume: ー Pages: 4987-4995
  • DOI: 10.1096/fj.201801868rr
  • NAID: 120006619816
  • Peer Reviewed
• [Journal Article] Somatic mutations in the human brain : implications for psychiatric research (2019)
  • Author(s): Nishioka M, Bundo M, Iwamoto K, Kato T
  • Journal Title: Molecular Psychiatry Volume: - Pages: 839-856
  • DOI: 10.1038/s41380-018-0129-y
  • Peer Reviewed / Open Access
• [Journal Article] Making psychiatry a clinical neuroscience-based medicine (2019)
  • Author(s): Kato Tadafumi、Kanba Shigenobu
  • Journal Title: Psychiatry and Clinical Neurosciences Volume: 73 Pages: 1-1
  • DOI: 10.1111/pcn.12798
  • Peer Reviewed
• [Journal Article] GABARAPs dysfunction by autophagy deficiency in adolescent brain impairs GABAA receptor trafficking and social behavior (2019)
  • Author(s): Hui Kelvin K.、Takashima Noriko、Watanabe Akiko、Chater Thomas E.、Matsukawa Hiroshi、Nekooki-Machida Yoko、Nilsson Per、Endo Ryo、Goda Yukiko、Saido Takaomi C.、Yoshikawa Takeo、Tanaka Motomasa
  • Journal Title: Sci Adv. Volume: 5
  • DOI: 10.1126/sciadv.aau8237
  • Peer Reviewed / Open Access
• [Journal Article] Key role of soluble epoxide hydrolase in the neurodevelopmental disorders of offspring after maternal immune activation (2019)
  • Author(s): Ma Min、Ren Qian、Yang Jun、Zhang Kai、Xiong Zhongwei、Ishima Tamaki、Pu Yaoyu、Hwang Sung Hee、Toyoshima Manabu、Iwayama Yoshimi、Hisano Yasuko、Yoshikawa Takeo、Hammock Bruce D.、Hashimoto Kenji
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 116 Pages: 7083-7088
  • DOI: 10.1073/pnas.1819234116
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Evaluation of the role of fatty acid-binding protein 7 in controlling schizophrenia-relevant phenotypes using newly established knockout mice (2019)
  • Author(s): Shimamoto-Mitsuyama Chie、Ohnishi Tetsuo、Balan Shabeesh、Ohba Hisako、Watanabe Akiko、Maekawa Motoko、Hisano Yasuko、Iwayama Yoshimi、Owada Yuji、Yoshikawa Takeo
  • Journal Title: Schizophrenia Research Volume: -
  • DOI: 10.1016/j.schres.2019.02.002
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Autophosphorylation of F-actin binding domain of CaMKIIβ is required for fear learning (2019)
  • Author(s): Kim Karam、Suzuki Akio、Kojima Hiroto、Kawamura Meiko、Miya Ken、Abe Manabu、Yamada Ikuko、Furuse Tamio、Wakana Shigenaru、Sakimura Kenji、Hayashi Yasunori
  • Journal Title: Neurobiology of Learning and Memory Volume: 157 Pages: 86-95
  • DOI: 10.1016/j.nlm.2018.12.003
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents. (2018)
  • Author(s): Tainaka K. Murakami TC, Susaki EA, Shimizu C, Saito R, Takahashi K, Hayashi-Takagi A, Sekiya H, Arima Y, Nojima S, Ikemura M, Ushiku T, Shimizu Y, Murakami M, Tanaka KF, Iino M, Kasai H, Sasaoka T. Kobayashi K, Miyazono K, Morii E, Isa T, Fukayama M, Kakita A. Ueda HR.
  • Journal Title: Cell Reports Volume: 24 Pages: 2196-2210
  • DOI: 10.1016/j.celrep.2018.07.056
  • NAID: 120006542018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pathological alterations of chondroitin sulfate moiety in postmortem hippocampus of patients with schizophrenia (2018)
  • Author(s): Yukawa t, Iwakura Y, Takei N, Saito M, Watanabe Y, Toyooka K, Igarashi, M, Niizato K, Oshima K, Kunii Y, Yabe H, Matsumoto J, Wada A, Hino M, Iritani S, Niwa S, Takeuchi R. Takahashi H, Kakita A, Someya T, *Nawa H
  • Journal Title: Psychiatry Res Volume: 270 Pages: 940-946
  • DOI: 10.1016/j.psychres.2018.10.062
  • Peer Reviewed / Open Access
• [Journal Article] Trans-omic Analysis Reveals Selective Responses to Induced and Basal Insulin across Signaling, Transcriptional, and Metabolic Networks (2018)
  • Author(s): Kawata Kentaro、Hatano Atsushi、Yugi Katsuyuki、Kubota Hiroyuki、Sano Takanori、Fujii Masashi、Tomizawa Yoko、Kokaji Toshiya、Tanaka Kaori Y.、Uda Shinsuke、Suzuki Yutaka、Matsumoto Masaki、Nakayama Keiichi I.、Saitoh Kaori、Kato Keiko、Ueno Ayano、Ohishi Maki、Hirayama Akiyoshi、Soga Tomoyoshi、Kuroda Shinya
  • Journal Title: iScience Volume: 7 Pages: 212-229
  • DOI: 10.1016/j.isci.2018.07.022
  • Peer Reviewed / Open Access
• [Journal Article] Mitochondrial dysfunction causes hyperexcitability of serotonergic neurons (2018)
  • Author(s): Kato Tomoaki M.、Kubota-Sakashita Mie、Fujimori-Tonou Noriko、Saitow Fumihito、Fuke Satoshi、Masuda Akira、Itohara Shigeyoshi、Suzuki Hidenori、Kato Tadafumi
  • Journal Title: Molecular Psychiatry Volume: 23 Pages: 1971-1971
  • DOI: 10.1038/s41380-018-0295-y
  • Peer Reviewed
• [Presentation] Multi-scale Understanding of Synaptic Pathology of Psychiatric Disorders (2021)
  • Author(s): Akiko Hayahshi-Takagi
  • Organizer: The 11th BRI Int'l Symposium
  • Int'l Joint Research / Invited
• [Presentation] Multi-scale Understanding of Synaptic Pathology of Psychiatric Disorders (2021)
  • Author(s): Akiko Hayahshi-Takagi
  • Organizer: 第98回日本生理学会大会
  • Invited
• [Presentation] Multi-scale Understanding of Synaptic Pathology of Psychiatric Disorders (2020)
  • Author(s): Akiko Hayahshi-Takagi
  • Organizer: 遺伝研研究会
  • Invited
• [Presentation] Multi-scale Understanding of Synaptic Pathology of Psychiatric Disorders (2020)
  • Author(s): Akiko Hayahshi-Takagi
  • Organizer: 第43回日本分子生物学会年会
  • Invited
• [Presentation] Multi-scale Understanding of Synaptic Pathology of Psychiatric Disorders (2019)
  • Author(s): Akiko Hayahshi-Takagi
  • Organizer: 1st international symposium of Multiscale Brain
  • Int'l Joint Research / Invited
• [Presentation] Intrinsic spine dynamics are critical for recurrent network learning in models with and without autism spectrum disorder (2019)
  • Author(s): Taro Toyoizumi
  • Organizer: 1st international symposium of Multiscale Brain
  • Int'l Joint Research / Invited
• [Presentation] Molecular mechanism of hippocampal synaptic plasticity (2019)
  • Author(s): Yasunori Hayashi
  • Organizer: 1st international symposium of Multiscale Brain
  • Int'l Joint Research / Invited
• [Presentation] Roles and mechanisms of neuroinflammation in stress and depression (2019)
  • Author(s): Tomyuki Furuyashiki
  • Organizer: 1st international symposium of Multiscale Brain
  • Invited
• [Remarks] マルチスケール精神病態の構成的理解
  • URL: http://multiscale-brain.umin.ne.jp/