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Research on neural circuit in decision-making by using cell- and projection-specific manner of chemogenetics and computational approach

Research Project

Project/Area Number 16H03303
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Basic / Social brain science
Research InstitutionNagoya University

Principal Investigator

Mizoguchi Hiroyuki  名古屋大学, 環境医学研究所, 講師 (70402568)

Research Collaborator YAMANAKA akihiro  
OHIRA hideki  
KATAHIRA kentaro  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Keywords意思決定 / DREADD / 島皮質 / 神経回路 / 精神疾患 / DREADD
Outline of Final Research Achievements

Decision-making is a key activity process that influences many aspects of daily living and both mental and physical health. In general, healthy participants reveal rational choice, but patients with neuropsychiatric disorders reveal irrational and risky choice in decision-making. A better understanding of the mechanisms underlying altered decision-making would provide insights into potential therapeutic approaches for these diseases. However, the neural pathway and substrates underlying these deficits are particularly unknown. In this research, we demonstrated that insular cortex, nucleus accumbens, and striatum are key regions for risky decision-making. Our findings suggest that disinhibition of glutamatergic neurons as well as dysfunction of GABAergic interneurons in the insular cortex, plays a role in altered decision-making. Further research on the insular-striatal pathway would be necessary to understand the mechanisms underlying impaired decision-making.

Academic Significance and Societal Importance of the Research Achievements

本研究により意思決定に関わる神経回路および分子機構を解明することができ、高次脳機能の根本的理解が進み、神経精神薬理学の分野に留まらず、脳科学の発展に大きく貢献できた。また、社会的問題として取り上げられているゲーム依存やギャンブル依存といった意思決定の異常を伴う多くの神経精神疾患の病態の解明と治療薬の開発につながる成果である。臨床研究と基礎研究をつなぐトランスレーショナルテスト・動物モデルとして、今後の創薬研究において極めて有用な研究成果である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (31 results)

All 2019 2018 2017 2016

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (25 results) (of which Int'l Joint Research: 3 results,  Invited: 5 results)

  • [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
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nicotine and varenicline ameliorate changes in reward-based choice strategy and altered decision-making in methamphetamine-treated rats.2019

    • Author(s)
      Mizoguchi H, Wang T, Kusaba M, Fukumoto K, Yamada K.
    • Journal Title

      Behav Brain Res.

      Volume: 359 Pages: 935-941

    • DOI

      10.1016/j.bbr.2018.06.016

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maternal separation as a risk factor for aggravation of neuropathic pain in later life in mice.2019

    • Author(s)
      Mizoguchi H, Fukumoto K, Sakamoto G, Jin S, Toyama A, Wang T, Suzumura A, Sato J.
    • Journal Title

      Behav Brain Res.

      Volume: 359 Pages: 942-949

    • DOI

      10.1016/j.bbr.2018.06.015

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Methamphetamine use causes cognitive impairment and altered decision-making.2019

    • Author(s)
      Mizoguchi H, Yamada K.
    • Journal Title

      Neurochem Int.

      Volume: 124 Pages: 106-113

    • DOI

      10.1016/j.neuint.2018.12.019

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ギャンブル障害の現状と薬剤師の役割.2018

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

      医薬ジャーナル

      Volume: 54(4) Pages: 1037-1040

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disrupted axon-glia interactions at the paranode in myelinated nerves cause axonal degeneration and neuronal cell death in the aged Caspr mutant mouse shambling2016

    • Author(s)
      Takagishi, Y., Katanosaka, K., Mizoguchi, H., Murata, Y
    • Journal Title

      Neurobiology of Aging

      Volume: 43 Pages: 34-46

    • DOI

      10.1016/j.neurobiolaging.2016.03.020

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] Optimization of operant test for testing risky decision-making in mice.2019

    • Author(s)
      Mizoguchi H、Wang T、Saifullah Md. Ali Bin 、Fukumoto K、 Mizoguchi H、Yamada K.
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Behavioral characterization of APP knock-in mice model in touchscreen-based tests aiming early detection of Alzheimer’s disease.2019

    • Author(s)
      Saifullah Md. Ali Bin、Komine O、Sobue A、Yamanaka K、Mizoguchi H.
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 基礎研究から探る覚せい剤依存の脳内機序.2018

    • Author(s)
      溝口博之.
    • Organizer
      第53回アルコール・アディクション医学会学術総会.
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Roots of risky decisions in addiction.2018

    • Author(s)
      Mizoguchi H.
    • Organizer
      The 4th IMCR Symposium on Endocrine and Metabolism
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 依存性薬物がもたらす認知・行動選択異常の解明に向けた基礎研究.2018

    • Author(s)
      溝口博之.
    • Organizer
      第28回日本臨床精神神経薬理学会・第48回日本神経精神薬理学会合同年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Roots of risky decisions in drug dependence.2018

    • Author(s)
      Mizoguchi H、Yamada K.
    • Organizer
      10th International Symposium on Cell/Tissue Injury and Cytoprotection/Organoprotection
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] An Operant task for testing risky decision-making in mice.2018

    • Author(s)
      Wang T、Fukumoto K、 Mizoguchi H、Yamada K.
    • Organizer
      19th World Congress of International-Society-for-Biomedical-Research-on-Alcoholism (ISBRA)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Ventral pallidum neurons control aversive learning.2018

    • Author(s)
      Macpherson T、Mizoguchi H、Yamanaka A、Hikida T.
    • Organizer
      Society for Neuroscience 2018 Annual Meeting
    • Related Report
      2018 Annual Research Report
  • [Presentation] Monomeric and dimeric RFP-dependent Cre and its application to detect glucocorticoid receptor activation.2018

    • Author(s)
      Inutsuka A、Mizoguchi H、Kaneko R、Nomura R、Takanami K、Sakamoto H、Onaka T.
    • Organizer
      Society for Neuroscience 2018 Annual Meeting
    • Related Report
      2018 Annual Research Report
  • [Presentation] Roles of orexin neurons in motivated behaviors in rats.2018

    • Author(s)
      Mizoguchi H、Inutsuka A、Katahira K、Yamada K、Yamanaka A.
    • Organizer
      The 7th Annual IIIS Symposium ~Solving the mystery of sleep~
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ラットの動機づけ行動におけるオレキシン神経の役割.2018

    • Author(s)
      溝口博之、犬束 歩、片平健太郎、山田清文、山中章弘.
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Ventral pallidum neurons control aversive learning.2018

    • Author(s)
      Macpherson T、 Mizoguchi H、Yamanaka A、Hikida T.
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 依存症抑止に向けた認知・意思決定異常の解明.2018

    • Author(s)
      溝口博之、山田清文.
    • Organizer
      第53回アルコール・アディクション医学会学術総会.
    • Related Report
      2018 Annual Research Report
  • [Presentation] 認知症との共生社会を支える基礎研究.2018

    • Author(s)
      溝口博之.
    • Organizer
      日本心理学会第82回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 食欲、報酬に対する動機づけ、意思決定におけるオレキシンの役割.2018

    • Author(s)
      溝口博之.
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] タッチスクリーン式弁別課題を用いた認知機能解析システムの確立2018

    • Author(s)
      Md.Ali Bin Saifullah, 山中宏二,溝口博之
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 依存性薬物がもたらす認知・意思決定異常2017

    • Author(s)
      溝口博之,山田清文
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 島皮質GABA神経の機能操作は意思決定に影響する2017

    • Author(s)
      溝口博之,犬束 歩,片平健太郎,山田清文
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] タッチスクリーン式弁別課題を用いた認知機能解析システムの確立2017

    • Author(s)
      Md.Ali-Bin-Saifullah,溝口博之
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] リスク下の意思決定における島皮質GABA神経の役割2017

    • Author(s)
      溝口博之,犬束 歩,片平健太郎,山田清文
    • Organizer
      平成29年度アルコール・薬物依存関連学会合同学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Nicotinic acetylcholine receptor as a target of harm reduction and treatment in addiction.2016

    • Author(s)
      Mizoguchi H, Yamada K
    • Organizer
      第51回日本アルコール・アディクション医学会学術総会
    • Place of Presentation
      東京
    • Year and Date
      2016-10-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 意思決定障害と創薬標的としてのニコチン受容体2016

    • Author(s)
      溝口博之、山田清文
    • Organizer
      第18回応用薬理シンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2016-08-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] 島皮質GABA神経は薬物依存ラットの意思決定に関与する2016

    • Author(s)
      溝口博之、山田清文
    • Organizer
      第39回日本神経科学会
    • Place of Presentation
      横浜
    • Year and Date
      2016-07-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] 薬物依存症における意思決定異常2016

    • Author(s)
      溝口博之、山田清文
    • Organizer
      第46回日本神経精神薬理学会
    • Place of Presentation
      ソウル
    • Year and Date
      2016-07-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] 薬物依存における意思決定と島皮質機能障害2016

    • Author(s)
      溝口博之
    • Organizer
      第34回日本生理心理学会大会
    • Place of Presentation
      名古屋
    • Year and Date
      2016-05-14
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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