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Roles of dopamine and serotonin in regulating motivation

Research Project

Project/Area Number 18H04037
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 51:Brain sciences and related fields
Research InstitutionNational Institutes for Quantum Science and Technology

Principal Investigator

Minamimoto Takafumi  国立研究開発法人量子科学技術研究開発機構, 量子医科学研究所 脳機能イメージング研究部, 上席研究員 (50506813)

Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥43,940,000 (Direct Cost: ¥33,800,000、Indirect Cost: ¥10,140,000)
Fiscal Year 2022: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2021: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2020: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2019: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2018: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Keywordsドーパミン / セロトニン / 意欲 / 報酬 / 価値 / 化学遺伝学 / DREADDs / モチベーション / サル / 脳・神経 / イメージング / 操作技術 / DREADD
Outline of Final Research Achievements

We investigated the mechanisms of motivation regulation involving dopamine and serotonin in macaque monkeys as a model for humans. Dopamine transmission was found to be involved in two distinct mechanisms of motivation regulation mediated by D1 and D2 receptors. In addition, we showed that serotonin transmission, specifically the reduction of serotonin signaling through 5-HT1B and 5-HT1A receptors, leads to a decrease in motivation that is dependent or independent of reward value, respectively. Together with the localization of these receptor subtypes, our findings provided insights into the neural circuits involved. Moreover, we advanced the application of chemogenetics, DREADDs, in macaque monkeys and successfully achieved selective and reversible control of dopamine neuron activity. These achievements hold great promise for advancing our understanding of monoamine control of motivation and the pathophysiology of mental disorders.

Academic Significance and Societal Importance of the Research Achievements

意欲制御の神経機構についてはドーパミンと腹側線条体を中心とするネットワークが関与することが知られている。一方で,意欲低下という症候を引き起こす「うつ」などの病態の背景にドーパミンとセロトニンレベルの低下が示唆されている.しかし,セロトニン低下が引き起こす意欲低下について,意欲制御の神経機構との関連から調べた研究はない。本成果によりドーパミンとセロトニン伝達低下がそれぞれもたらす意欲低下が数理モデルで説明できた。これらのモデルは正常から病態まで一貫して説明する意欲制御の神経機構を提供し、精神・神経疾患の病態理解の進展が期待できる。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (42 results)

All 2023 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (7 results) Journal Article (12 results) (of which Int'l Joint Research: 3 results,  Open Access: 11 results,  Peer Reviewed: 11 results) Presentation (18 results) (of which Int'l Joint Research: 7 results,  Invited: 15 results) Remarks (3 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] ICM/CNRS(フランス)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] NIH(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] ICM(フランス)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] U. North Carolina/Mt Sinai(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] National Institute of Health/Univ. North Carolina(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] CNRS(フランス)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Univ. South Carolina/Mount Sinai(米国)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Reduced serotonergic transmission alters sensitivity to cost and reward via 5-HT1A and 5-HT1B receptors in monkeys2023

    • Author(s)
      Hori Yukiko、Mimura Koki、Nagai Yuji、Hori Yuki、Kumata Katsushi、Zhang Ming-Rong、Suhara Tetsuya、Higuchi Makoto、Minamimoto Takafumi
    • Journal Title

      bioRxiv

    • DOI

      10.1101/2023.02.23.529630

    • Related Report
      2022 Annual Research Report
    • Open Access
  • [Journal Article] Chronic Behavioral Manipulation via Orally Delivered Chemogenetic Actuator in Macaques2022

    • Author(s)
      Oyama Kei、Hori Yukiko、Nagai Yuji、Miyakawa Naohisa、Mimura Koki、Hirabayashi Toshiyuki、Inoue Ken-ichi、Takada Masahiko、Higuchi Makoto、Minamimoto Takafumi
    • Journal Title

      The Journal of Neuroscience

      Volume: 42 Issue: 12 Pages: 2552-2561

    • DOI

      10.1523/jneurosci.1657-21.2021

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemogenetic sensory fMRI reveals behaviorally-relevant bidirectional changes in primate somatosensory network.2021

    • Author(s)
      Hirabayashi T, Nagai Y, Hori Y, Inoue KI, Aoki I, Takada M, Suhara T, Higuchi M, Minamimoto T.
    • Journal Title

      Neuron

      Volume: 109 Issue: 20 Pages: 3312-3322

    • DOI

      10.1016/j.neuron.2021.08.032

    • NAID

      120007166034

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemogenetic activation of nigrostriatal dopamine neurons in freely moving common marmosets.2021

    • Author(s)
      Mimura K, Nagai Y, Inoue K, Matsumoto J, Hori Y, Sato C, Kimura K, Okauchi T, Hirabayashi T, Nishijo H, Yahata N, Takada M, Suhara T, Higuchi M, Minamimoto T
    • Journal Title

      iScience

      Volume: 24(9) Issue: 9 Pages: 103066-103066

    • DOI

      10.1016/j.isci.2021.103066

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single caudate neurons encode temporally discounted value for formulating motivation for action.2021

    • Author(s)
      Hori Y, Mimura K, Nagai Y, Fujimoto A, Oyama K, Kikuchi E, Inoue KI, Takada M, Suhara T, Richmond BJ, Minamimoto T.
    • Journal Title

      eLife

      Volume: 10 Pages: 61248-61248

    • DOI

      10.7554/elife.61248

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] D1- and D2-like receptors differentially mediate the effects of dopaminergic transmission on cost-benefit evaluation and motivation in monkeys2021

    • Author(s)
      Hori Yukiko、Nagai Yuji、Mimura Koki、Suhara Tetsuya、Higuchi Makoto、Bouret Sebastien、Minamimoto Takafumi
    • Journal Title

      PLOS Biology

      Volume: 19 Issue: 7 Pages: 3001055-3001055

    • DOI

      10.1371/journal.pbio.3001055

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chemogenetic dissection of the primate prefronto-subcortical pathways for working memory and decision-making2021

    • Author(s)
      Oyama Kei、Hori Yukiko、Nagai Yuji、Miyakawa Naohisa、Mimura Koki、Hirabayashi Toshiyuki、Inoue Ken-ichi、Suhara Tetsuya、Takada Masahiko、Higuchi Makoto、Minamimoto Takafumi
    • Journal Title

      Science Advances

      Volume: 7 Issue: 26 Pages: 1-9

    • DOI

      10.1126/sciadv.abg4246

    • NAID

      120007089253

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deschloroclozapine, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys2020

    • Author(s)
      Nagai Yuji, Miyakawa Naohisa et al.
    • Journal Title

      Nature Neuroscience

      Volume: 23 Issue: 9 Pages: 1157-1167

    • DOI

      10.1038/s41593-020-0661-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Macaques Exhibit Implicit Gaze Bias Anticipating Others’ False-Belief-Driven Actions via Medial Prefrontal Cortex2020

    • Author(s)
      Hayashi Taketsugu、Akikawa Ryota、Kawasaki Keisuke、Egawa Jun、Minamimoto Takafumi、Kobayashi Kazuto、Kato Shigeki、Hori Yukiko、Nagai Yuji、Iijima Atsuhiko、Someya Toshiyuki、Hasegawa Isao
    • Journal Title

      Cell Reports

      Volume: 30 Issue: 13 Pages: 4433-4444

    • DOI

      10.1016/j.celrep.2020.03.013

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Trait and State-Dependent Risk Attitude of Monkeys Measured in a Single-Option Response Task2019

    • Author(s)
      Fujimoto Atsushi、Minamimoto Takafumi
    • Journal Title

      Frontiers in Neuroscience

      Volume: 13 Pages: 816-816

    • DOI

      10.3389/fnins.2019.00816

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Signaling Incentive and Drive in the Primate Ventral Pallidum for Motivational Control of Goal-Directed Action2019

    • Author(s)
      Fujimoto Atsushi、Hori Yukiko、Nagai Yuji、Kikuchi Erika、Oyama Kei、Suhara Tetsuya、Minamimoto Takafumi
    • Journal Title

      The Journal of Neuroscience

      Volume: 39 Issue: 10 Pages: 1793-1804

    • DOI

      10.1523/jneurosci.2399-18.2018

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recruitment of calbindin into nigral dopamine neurons protects against drug-induced parkinsonism. Mov Disord [Epub ahead of print] doi: 10.1002/mds.1072018

    • Author(s)
      Inoue K, Miyachi S, Nishi K, Okado H, Nagai Y, Minamimoto T, Nambu A, Takada M
    • Journal Title

      Mov Disord

      Volume: - Issue: 2 Pages: 200-209

    • DOI

      10.1002/mds.107

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] 化学遺伝学とイメージングの融合によるサル脳回路の可視化と機能理解2022

    • Author(s)
      南本 敬史
    • Organizer
      京都大学霊長類研究所共同利用研究会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Visualizing and manipulating primate brain circuits with DREADDs2022

    • Author(s)
      Minamimoto T.
    • Organizer
      7th CiNet Conference
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ドーパミン伝達による意欲調節機構:サル分子イメージングと行動薬理を用いた解析2021

    • Author(s)
      南本 敬史
    • Organizer
      大阪大学蛋白質研究所セミナー「多様なドーパミン神経伝達から 脳を探る」大阪大学 蛋白質研究所
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Neural mechanism for valuation and motivation in health and disease2021

    • Author(s)
      Minamimoto T, Hori Y, Oyama K
    • Organizer
      第44回日本神経科学大会, 神戸
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Interrogation of monkey brain circuits with imaging-guided chemogenetics2021

    • Author(s)
      Minamimoto T
    • Organizer
      ASPET 2021, American Society for Pharmacology and Experimental Therapeutics
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 1.Neural mechanisms of motivational control based on cost-benefit comparison in monkey2020

    • Author(s)
      Minamimoto T
    • Organizer
      第98回生理学学会大会シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Dopamine, Serotonin, and Motivation2020

    • Author(s)
      南本敬史
    • Organizer
      京都大学霊長類研究所 共同利用研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] モチベーションの脳内調節機構とその破綻2020

    • Author(s)
      南本敬史
    • Organizer
      日本心理学会第84回大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 化学遺伝学とイメージングの融合による霊長類脳回路の可視化と操作2020

    • Author(s)
      南本敬史
    • Organizer
      第9回マーモセット研究会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] DREADD inactivation reveals critical role of orbitofrontal cortex in reward-based adaptive decision-making in monkeys.2019

    • Author(s)
      Oyama K, Hori Y, Nagai Y, Hirabayashi T, Miyakawa N, Fujimoto A, Mimura K, Inoue K, Eldridge MAG, Saunders RC, Suhara T, Takada M, Higuchi M, Richmond BJ, Minamimoto T.
    • Organizer
      第42回日本神経科学大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] New DREADD compound enables to visualize and manipulate neural circuits in monkeys2019

    • Author(s)
      Minamimoto T
    • Organizer
      NIH BRAIN Initiative Chemogenetic Innovations in the Manipulation and Monitoring of Labeled Neurons Workshop
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 意欲調節の神経メカニズムとその障害―サル分子イメージングによる探索2019

    • Author(s)
      南本敬史、堀由紀子、永井裕司
    • Organizer
      「情動の生起と変容の多面的理解に向けて」情動研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Using PET imaging to monitor chemogenetic manipulation of nigrostriatal dopamine system in common marmoset.2018

    • Author(s)
      三村喬生, 永井裕司, 井上謙一, 須原哲也, 高田昌彦, 南本敬史,
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] PET imaging of selective control of neural activity with a novel DREADD agonist,2018

    • Author(s)
      Nagai Y, ほか26名、Minamimoto T.
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] PET imaging-guided chemogenetic modification of reward-related circuits in monkeys2018

    • Author(s)
      Minamimoto T.
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Chemogenetic imaging: monitoring and manipulating neural circuits in monkeys.2018

    • Author(s)
      Minamimoto T.
    • Organizer
      Viral Manipulation in Monkey, Paris
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A novel ligand C22b enables selective and rapid chemogenetic neuronal modification in monkeys.2018

    • Author(s)
      Minamimoto T.
    • Organizer
      Genetic Technologies for Systems Neuroscience in NHP, NIH, USA
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A chemogenetic toolbox for non-human primates2018

    • Author(s)
      Minamimoto T.
    • Organizer
      New Directions in Systems Neuroscience, Germany
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 量子科学技術研究開発機構 システム神経回路研究グループ

    • URL

      https://www.nirs.qst.go.jp/seika/brain/team/system_09.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] 量子科学技術研究開発機構 システム神経回路研究グループ

    • URL

      https://www.nirs.qst.go.jp/seika/brain/team/system_09.html

    • Related Report
      2021 Annual Research Report
  • [Remarks] システム神経回路研究グループ

    • URL

      https://www.nirs.qst.go.jp/seika/brain/team/system_09.html

    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 人工受容体に結合する新規化合物、人工受容体のイメージング方法、ア ゴニストまたはアンタゴニスト、治療薬、コンパニオン診断薬、神経細胞のイメージ ング方法2018

    • Inventor(s)
      南本敬史、永井裕司、季斌、宮川尚久、樋口真人、須原哲也
    • Industrial Property Rights Holder
      量子科学技術研究開発機構
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Acquisition Date
      2021
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 人工受容体に結合する新規化合物、人工受容体のイメージング方法、アゴニストまたはアンタゴニスト、治療薬、コンパニオン診断薬、神経細胞のイメージング方法2018

    • Inventor(s)
      南本敬史・永井裕司・季斌・宮川尚久・樋口真人・須原哲也
    • Industrial Property Rights Holder
      量子科学技術研究開発機構
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-118210
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2024-01-30  

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