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Neural basis of risky decision-making: Behavior, neural manipulation, computational approaches

Research Project

Project/Area Number 19H03532
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 51010:Basic brain sciences-related
Research InstitutionNagoya University

Principal Investigator

Mizoguchi Hiroyuki  名古屋大学, 医学部附属病院, 准教授 (70402568)

Co-Investigator(Kenkyū-buntansha) 犬束 歩  自治医科大学, 医学部, 助教 (30584776)
片平 健太郎  国立研究開発法人産業技術総合研究所, 情報・人間工学領域, 主任研究員 (60569218)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2020: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywordsリスク志向 / 意思決定 / 島皮質 / 大脳基底核
Outline of Research at the Start

依存症は健康を脅かす疾患であり、ギャンブル障害、ゲーム障害などが新たに精神疾患として認定されるなど、今まで以上に身近な社会問題として懸念されている。この事から新たな依存症の包括的理解に向けた機序解明が必要である。本研究では、多種多様な遺伝子発現制御法と遺伝子改変ラットを用いて、島皮質を基軸とした意思決定・行動選択の変容に関わる領域間ネットワーク、神経-神経ネットワークを解明し、依存症の新たな治療戦略の発信を目指す。

Outline of Final Research Achievements

In this research, we found that DRD2 deficits in striatum induce risk-aversive behavior: Flp/FRT system is powerful tool for manipulation of insular-striatum pathway: DRD2 is disrupted in DRD2-positive cells by CRISPR/Cas9 system. Thus, we established the in vivo method for manipulating neural circuits based on the insular cortex.

Academic Significance and Societal Importance of the Research Achievements

依存症は世界銀行・WHOが報告するDALY(障害調整生命年)によると、世界トップ10に入る健康を脅かす疾患であり、ギャンブル障害、ゲーム障害などが新たに精神疾患として認定されるなど、今まで以上に身近な社会問題として懸念されている。リスク志向な行動異常を解明するためには、より細胞特異性の高い操作方法が求められている。その点から考えると、本研究成果は島皮質がリスク志向な意思決定のハブ領域であることを見つけるための手法を確立することができ、行動実験などの応用性が期待できる成果となった。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (26 results)

All 2022 2021 2020 2019

All Journal Article (10 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 10 results,  Open Access: 9 results) Presentation (16 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] New Strategies for the Treatment of Neuropsychiatric Disorders Based on Reelin Dysfunction2022

    • Author(s)
      Tsuneura Yumi、Nakai Tsuyoshi、Mizoguchi Hiroyuki、Yamada Kiyofumi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 3 Pages: 1829-1829

    • DOI

      10.3390/ijms23031829

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mice with exonic RELN deletion identified from a patient with schizophrenia have impaired visual discrimination learning and reversal learning in touchscreen operant tasks2022

    • Author(s)
      Liao Jingzhu、Dong Geyao、Wulaer Bolati、Sawahata Masahito、Mizoguchi Hiroyuki、Mori Daisuke、Ozaki Norio、Nabeshima Toshitaka、Nagai Taku、Yamada Kiyofumi
    • Journal Title

      Behavioural Brain Research

      Volume: 416 Pages: 113569-113569

    • DOI

      10.1016/j.bbr.2021.113569

    • NAID

      120007190677

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Alzheimer’s Disease Animal Models: Elucidation of Biomarkers and Therapeutic Approaches for Cognitive Impairment2021

    • Author(s)
      Nakai Tsuyoshi、Yamada Kiyofumi、Mizoguchi Hiroyuki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 11 Pages: 5549-5549

    • DOI

      10.3390/ijms22115549

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mice carrying a schizophrenia-associated mutation of the Arhgap10 gene are vulnerable to the effects of methamphetamine treatment on cognitive function: association with morphological abnormalities in striatal neurons2021

    • Author(s)
      Hada K, Wulaer B, Nagai T, Itoh N, Sawahata M, Sobue A, Mizoguchi H, Mori D, Kushima I, Nabeshima T, Ozaki N, Yamada K.
    • Journal Title

      Mol Brain

      Volume: 14(1) Issue: 1 Pages: 21-21

    • DOI

      10.1186/s13041-021-00735-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of Reelin signaling and neurodevelopmental trajectory in primary cultured cortical neurons with RELN deletion identified in schizophrenia2021

    • Author(s)
      Tsuneura Yumi、Sawahata Masahito、Itoh Norimichi、Miyajima Ryoya、Mori Daisuke、Kohno Takao、Hattori Mitsuharu、Sobue Akira、Nagai Taku、Mizoguchi Hiroyuki、Nabeshima Toshitaka、Ozaki Norio、Yamada Kiyofumi
    • Journal Title

      Neurochemistry International

      Volume: 144 Pages: 104954-104954

    • DOI

      10.1016/j.neuint.2020.104954

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Microglial gene signature reveals loss of homeostatic microglia associated with neurodegeneration of Alzheimer’s disease2021

    • Author(s)
      Sobue Akira、Komine Okiru、Hara Yuichiro、Endo Fumito、Mizoguchi Hiroyuki、Watanabe Seiji、Murayama Shigeo、Saito Takashi、Saido Takaomi C.、Sahara Naruhiko、Higuchi Makoto、Ogi Tomoo、Yamanaka Koji
    • Journal Title

      Acta Neuropathologica Communications

      Volume: 9 Issue: 1 Pages: 111111-111111

    • DOI

      10.1186/s40478-020-01099-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Touchscreen-based location discrimination and paired associate learning tasks detect cognitive impairment at an early stage in an App knock-in mouse model of Alzheimer's disease2020

    • Author(s)
      Saifullah MAB, Komine O, Dong Y, Fukumoto K, Sobue A, Endo F, Saito T, Saido TC, Yamanaka K, Mizoguchi H.
    • Journal Title

      Mol Brain.

      Volume: 13(1) Issue: 1 Pages: 147-147

    • DOI

      10.1186/s13041-020-00690-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preproenkephalin-expressing ventral pallidal neurons control inhibitory avoidance learning. 2019 (in press)2019

    • Author(s)
      Macpherson T, Mizoguchi H, Yamanaka A, Hikida T
    • Journal Title

      Neurochem Int

      Volume: 126 Pages: 11-18

    • DOI

      10.1016/j.neuint.2019.02.011

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] REM sleep?active MCH neurons are involved in forgetting hippocampus-dependent memories2019

    • Author(s)
      Izawa Shuntaro、Chowdhury Srikanta、Miyazaki Toh、Mukai Yasutaka、Ono Daisuke、Inoue Ryo、Ohmura Yu、Mizoguchi Hiroyuki、Kimura Kazuhiro、Yoshioka Mitsuhiro、Terao Akira、Kilduff Thomas S.、Yamanaka Akihiro
    • Journal Title

      Science

      Volume: 365 Issue: 6459 Pages: 1308-1313

    • DOI

      10.1126/science.aax9238

    • NAID

      120006777541

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Physiological centers of decision-making: manipulation of neural activity in insular cortex by AAV2019

    • Author(s)
      溝口 博之, 山田 清文.
    • Journal Title

      Folia Pharmacologica Japonica

      Volume: 153 Issue: 5 Pages: 224-230

    • DOI

      10.1254/fpj.153.224

    • NAID

      130007649350

    • ISSN
      0015-5691, 1347-8397
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] Dynamic changes in orexin activities in reward-based motivative behavior.2022

    • Author(s)
      Yutao Dong、 溝口博之、 山中章弘、山田清文
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 報酬獲得行動に関わる脳内ネットワークの追究2021

    • Author(s)
      溝口博之
    • Organizer
      2021年度アルコール・薬物依存関連学会合同学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 依存症がもたらす意思決定異常と脳内報酬系2021

    • Author(s)
      溝口博之
    • Organizer
      2021年度アルコール・薬物依存関連学会合同学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Activities of orexin neurons in motivative behavior.2021

    • Author(s)
      Yutao Dong、溝口博之、山中章弘、山田清文
    • Organizer
      第139回日本薬理学会近畿部会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 認知症早期発見と創薬への行動薬理学研究者の挑戦.2020

    • Author(s)
      溝口博之、山中宏二.
    • Organizer
      第30回日本医療薬学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 依存症の理解に向けた意思決定の神経回路の解明.2020

    • Author(s)
      溝口博之、山田清文、山中章弘.
    • Organizer
      第43回日本神経科学大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 意思決定異常に対する創薬標的:バレニクリンの有効性.2020

    • Author(s)
      溝口博之、山田清文
    • Organizer
      第137回日本薬理学会近畿部会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 動機づけ行動におけるオレキシン神経の役割2020

    • Author(s)
      溝口 博之、犬束 歩、片平 健太郎、山田 清文、山中 章弘.
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] タッチスクリーン式学習試験法はアルツハイマー病モデル動物の早期の認知機能障害を検出できる.2020

    • Author(s)
      溝口博之、小峯 起、Md. Ali Bin Saifullah1、祖父江 顕、遠藤史人、山中宏二.
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Roots of decision-making in addiction: the insular cortex, nucleus accumbens, striatum.2019

    • Author(s)
      Mizoguchi H.
    • Organizer
      7th Meeting of the International Drug Abuse Research Society (IDARS)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Roles of orexin neurons in motivated behaviors in rats.2019

    • Author(s)
      Mizoguchi H, Inutsuka A, Katahira K, Yamada K, Yamanaka A.
    • Organizer
      6th Congress of Asian College of Neuropsycopharmacology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Touchscreen-based tests detect cognitive impairment at an early stage in APP knock-in mice model.2019

    • Author(s)
      Saifullah Md. Ali Bin , Komine O, Sobue A, Yamanaka K, Mizoguchi H.
    • Organizer
      6th Congress of Asian College of Neuropsychopharmacology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 依存症における意思決定の神経回路:島皮質と線条体.2019

    • Author(s)
      溝口博之、山田清文
    • Organizer
      第42回日本神経科学大会第62回日本神経化学会大会,
    • Related Report
      2019 Annual Research Report
  • [Presentation] 食欲、報酬に対する動機づけにおけるオレキシン神経の役割2019

    • Author(s)
      溝口博之
    • Organizer
      第4 回食欲・食嗜好の分子・神経基盤研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 依存症における意思決定異常と島皮質GABA神経2019

    • Author(s)
      溝口博之、山田清文
    • Organizer
      第49回日本神経精神薬理学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 報酬に対する動機づけにおけるオレキシン神経の役割.2019

    • Author(s)
      溝口博之.
    • Organizer
      日本病院薬剤師会東海ブロック・日本薬学会東海支部合同学術大会
    • Related Report
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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