Analysis of neural circuitry and regulatory mechanisms of social behavior adjustment to social environment

• Project/Area Number: 16K01948
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Basic / Social brain science
• Research Institution: Kyoto University
• Principal Investigator: Sakurai Takeshi 京都大学, 医学研究科, 特定教授 (90615717)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 社会性行動 / マウスモデル

Outline of Final Research Achievements

We have shown that behavioral alterations observed in model mouse that mimics Williams Beuren syndrome, a developmental neuropsychiatric disorder in humans in humans may be caused by alterations in neural circuitry involving prefrontal cortex and thalamus and in neuromodulatory system including oxytocin and vasopressin.

Academic Significance and Societal Importance of the Research Achievements

ウィリアムス・ビューレン症候群は染色体のある領域の欠損で起こる過剰な社会性行動を特徴とする疾患で、自閉症の対極をなす症状を示すものとして注目されて来た。過剰な社会性行動を含む様々な社会性行動の異常は自閉症をはじめ様々な精神疾患に伴って見られる行動表現型であるが、その異常に前頭前野や視床を含む脳神経回路やその調節系であるオキシトシンやバゾプレシンの発達異常が関与している可能性が示唆された。

Research Products

• [Int'l Joint Research] Johns Hopkins University(米国)
• [Int'l Joint Research] University of Toronto(カナダ)
• [Int'l Joint Research] Johns Hopkins University(米国)
• [Int'l Joint Research] University of Toronto(Canada)
• [Journal Article] Ulk2 controls cortical excitatory?inhibitory balance via autophagic regulation of p62 and GABAA receptor trafficking in pyramidal neurons (2018)
  • Author(s): Sumitomo Akiko、Yukitake Hiroshi、Hirai Kazuko、Horike Kouta、Ueta Keisho、Chung Youjin、Warabi Eiji、Yanagawa Toru、Kitaoka Shiho、Furuyashiki Tomoyuki、Narumiya Shuh、Hirano Tomoo、Niwa Minae、Sibille Etienne、Hikida Takatoshi、Sakurai Takeshi、Ishizuka Koko、Sawa Akira、Tomoda Toshifumi
  • Journal Title: Human Molecular Genetics Volume: 27 Issue: 18 Pages: 3165-3176
  • DOI: 10.1093/hmg/ddy219
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A mouse model of 22q11.2 deletions: Molecular and behavioral signatures of Parkinson’s disease and schizophrenia (2018)
  • Author(s): Sumitomo Akiko、Horike Kouta、Hirai Kazuko、Butcher Nancy、Boot Erik、Sakurai Takeshi、Nucifora Frederick C.、Bassett Anne S.、Sawa Akira、Tomoda Toshifumi
  • Journal Title: Science Advances Volume: 4 Issue: 8
  • DOI: 10.1126/sciadv.aar6637
  • NAID: 120006510283
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neuronal cell adhesion molecule regulating neural systems underlying addiction (2018)
  • Author(s): Ishiguro Hiroki、Miyake Kunio、Tabata Koichi、Mochizuki Chiaki、Sakurai Takeshi、Onaivi Emmanuel S.
  • Journal Title: Neuropsychopharmacology Reports Volume: 39 Issue: 1 Pages: 10-16
  • DOI: 10.1002/npr2.12038
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characterizing vulnerable brain areas and circuits in mouse models of autism: Towards understanding pathogenesis and new therapeutic approaches. (2018)
  • Author(s): Hui K, Katayama Y, Nakayama KI, Nomura J, Sakurai T.
  • Journal Title: Neurosci. Biobehav. Rev. Volume: 印刷中 Pages: 30121-0
  • DOI: 10.1016/j.neubiorev.2018.08.001
  • Peer Reviewed
• [Journal Article] Cognitive functions associated with developing prefrontal cortex during adolescence and developmental neuropsychiatric disorders (2018)
  • Author(s): Sakurai Takeshi、Gamo Nao J.
  • Journal Title: Neurobiology of Disease Volume: in press Pages: 104322-104322
  • DOI: 10.1016/j.nbd.2018.11.007
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 脳神経回路と精神生物学：神経機能と心の根源を探る、２、神経回路と脳機能 (2018)
  • Author(s): 櫻井武、友田利文
  • Journal Title: Clinical Calcium Volume: 28 Pages: 844-850
  • Int'l Joint Research
• [Journal Article] 神経回路形成に働く遺伝子群 シナプス形成 (2018)
  • Author(s): 櫻井武 谷口智彦 中村大和
  • Journal Title: Clinical Neuroscience Volume: 36 Pages: 176-180
• [Journal Article] Methylphenidate and Guanfacine Ameliorate ADHD-Like Phenotypes in <b><i>Fez1</i></b>-Deficient Mice (2017)
  • Author(s): Sumitomo Akiko、Saka Ayumi、Ueta Keisho、Horike Kouta、Hirai Kazuko、Gamo Nao J.、Hikida Takatoshi、Nakayama Keiichi I.、Sawa Akira、Sakurai Takeshi、Tomoda Toshifumi
  • Journal Title: Molecular Neuropsychiatry Volume: 3 Issue: 4 Pages: 223-233
  • DOI: 10.1159/000488081
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The roles of cell adhesion molecules in brain wiring and neuropsychiatric disorders. (2017)
  • Author(s): Takeshi Sakurai
  • Journal Title: Molecular and Cellular Neuroscience Volume: in press Pages: 4-11
  • DOI: 10.1016/j.mcn.2016.08.005
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Role of DISC1 in Neuronal Trafficking and its Implication in Neuropsychiatric Manifestation and Neurotherapeutics (2017)
  • Author(s): Tomoda Toshifumi、Hikida Takatoshi、Sakurai Takeshi
  • Journal Title: Neurotherapeutics Volume: 14 Issue: 3 Pages: 623-629
  • DOI: 10.1007/s13311-017-0556-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Circuitry-Based Human Neuroanatomy for the Next Generation in Psychiatry and Neuroscience (2017)
  • Author(s): Sakurai Takeshi
  • Journal Title: Molecular Neuropsychiatry Volume: 3 Issue: 2 Pages: 92-96
  • DOI: 10.1159/000479514
  • Peer Reviewed
• [Journal Article] Ulk1 protects against ethanol-induced neuronal stress and cognitive deficits in object discrimination. (2017)
  • Author(s): Akiko Sumitomo, Keisho Ueta, Sayaka Mauchi, Kazuko Hirai, Kouta Horike, Takatoshi Hikida, Takeshi Sakurai, Akira Sawa, Toshifumi Tomoda
  • Journal Title: Neuroscience Research Volume: in press Pages: 54-61
  • DOI: 10.1016/j.neures.2016.12.004
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Valley of death: A proposal to build a “translational bridge” for the next generation. (2017)
  • Author(s): Nao J. Gamo, Michelle R. Birknow, Danielle Sullivan, Mari A. Kondo, Yasue Horiuchi, Takeshi Sakurai, Barbara S. Slusher, Akira Sawa.
  • Journal Title: Neuroscience Research Volume: in press Pages: 1-4
  • DOI: 10.1016/j.neures.2016.11.003
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Development and function of mouse prefrontal cortex (2017)
  • Author(s): Takeshi Sakurai, Yamato Nakamura
  • Organizer: Cold spring harbor meeting, wiring the brain
  • Place of Presentation: Cold spring harbor, New York, USA
  • Year and Date: 2017-04-04
  • Int'l Joint Research
• [Presentation] Analysis of mouse models for psychiatric disorders with social behavior alterations. (2017)
  • Author(s): Takeshi Sakurai, Yamato Nakamura
  • Organizer: Annual meeting of International Behavioral Neuroscience Society
  • Int'l Joint Research / Invited
• [Presentation] Development and function of mouse prefrontal cortex. (2017)
  • Author(s): Takeshi Sakurai, Yamato Nakamura
  • Organizer: Cold Spring Harbor Meeting, “Wiring the brain”
  • Int'l Joint Research
• [Book] Chapter in "Charney and Nestler’s Neurobiology of Mental Illness, 5th edition" (2018)
  • Author(s): Nao J. Gamo, Takeshi Sakurai, Hanna Jaaro-Peled, and Akira Sawa
  • Publisher: Oxford University Press
  • ISBN: 9780190681425