Neural mechanisms underlying inhibition of habits

• Project/Area Number: 17H04749
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Developmental mechanisms and the body works
• Research Institution: Tohoku University (2022); Okinawa Institute of Science and Technology Graduate University (2017-2019)
• Principal Investigator: Aoki Sho 東北大学, 生命科学研究科, 助教 (80720672)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000); Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2017: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
• Keywords: 線条体 / アセチルコリン / 習慣的動作 / 大脳基底核 / 習慣 / 行動 / 動作 / イメージング / 手続き記憶 / マウス / 動作の癖 / 大脳皮質 / 上丘 / 手続き学習 / 前頭前野 / 習慣的行動 / 小脳 / 動物モデル / 神経活動操作 / 動きの癖

Outline of Final Research Achievements

I have investigated neural mechanisms underlying suppression of habitual motor behavior. First, I developed an operant conditioning paradigm in which rats need to inhibit or switch a habitual movement. To investigate its mechanism, I focused on striatal cholinergic interneurons and found its role in modifying habitual motor behavior. For further investigation of the neural mechanism, I decided to use mice as it enables to apply various approaches of molecular biology and genetics, and developed another version of the action sequencing task in mice. In summary, the outcome of this research contributes to our understanding of how animals suppress or modify a habitual movement, and provide a foundation to future studies to investigate its neural underpinnings.

Academic Significance and Societal Importance of the Research Achievements

動作の癖はどのようにすれば直すことが出来るのか。この問題は、スポーツ指導や学校教育現場において、競技者のみならず指導者が直面する難題である。本研究は、動物モデルを用いて動きの癖を抑制・改善する神経メカニズムの解明に挑んだ。その結果、大脳基底核・線条体で神経伝達物質アセチルコリンを放出するコリン作動性介在ニューロンが重要な役割を果たすことが明らかになった。これは習慣化した動作の抑制・切り替えを担う神経メカニズムの一端を明らかにした重要研究知見といえる。今後、より詳細なメカニズムを解明していくことで、動作の癖を直す神経機構の基本的理解が進むことが期待される。

Research Products

• [Int'l Joint Research] Salk Institute for Biological Studies(米国)
• [Int'l Joint Research] Erasmus Medical Center Rotterdam(オランダ)
• [Int'l Joint Research] Salk Institute for Biological Studies(米国)
• [Int'l Joint Research] Erasmus Medical Center(オランダ)
• [Int'l Joint Research] Salk Insititute(米国)
• [Journal Article] An open cortico-basal ganglia loop allows limbic control over motor output via the nigrothalamic pathway (2019)
  • Author(s): Sho Aoki, Jared B. Smith, Hao Li, Xunyi Yan, Masakazu Igarashi, Patrice Coulon, Jeffery R. Wickens, Tom J.H. Ruigrok, Xin Jin
  • Journal Title: eLife Volume: 8 Pages: 49995-49995
  • DOI: 10.7554/elife.49995
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cerebellar modules and their role as operational cerebellar processing units. (2018)
  • Author(s): Richard Apps, Richard Hawkes, Sho Aoki, Amanda M. Brown, Gang Chen, Timothy J. Ebner, Philippe Isope, Elizabeth P. Lackey, Charlotte Lawrenson, Bridget Lumb, Martijn Schonewille, Roy V. Sillitoe, Ludovic Spaeth, Izumi Sugihara, Antoine Valera, Jan Voogd, Douglas R. Wylie Tom J.H. Ruigrok
  • Journal Title: The Cerebellum Volume: 17 Issue: 5 Pages: 654-682
  • DOI: 10.1007/s12311-018-0952-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cholinergic interneurons in the rat striatum modulate substitution of habits (2018)
  • Author(s): Sho Aoki, Andrew W. Liu, Yumiko Akamine, Aya Zucca, Stefano Zucca, Jeffery R. Wickens
  • Journal Title: European Journal of Neuroscience Volume: 47 Issue: 10 Pages: 1194-1205
  • DOI: 10.1111/ejn.13820
  • Peer Reviewed / Open Access
• [Journal Article] Pauses in cholinergic interneuron firing exert an inhibitory control on striatal output in vivo (2018)
  • Author(s): Zucca Stefano、Zucca Aya、Nakano Takashi、Aoki Sho、Wickens Jeffery
  • Journal Title: eLife Volume: 7
  • DOI: 10.7554/elife.32510
  • Peer Reviewed / Open Access
• [Journal Article] Multizonal Cerebellar Influence Over Sensorimotor Areas of the Rat Cerebral Cortex (2017)
  • Author(s): Aoki Sho、Coulon Patrice、Ruigrok Tom J H
  • Journal Title: Cerebral Cortex Volume: in press Issue: 2 Pages: 598-614
  • DOI: 10.1093/cercor/bhx343
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Linking emotion to motion: an open cortico-basal ganglia loop allows limbic control over motor output (2019)
  • Author(s): Sho Aoki
  • Organizer: Neuro2019
  • Invited
• [Presentation] Linking emotion to motion: novel interaction across “limbic” and “motor” cortico-basal ganglia loops. (2019)
  • Author(s): Sho Aoki
  • Organizer: OIST workshop: Neural Circuits for Motor Behavior
  • Int'l Joint Research / Invited
• [Presentation] Multiple viral tracings reveal an anatomical hierarchy in cortico-basal ganglia loops. (2018)
  • Author(s): Sho Aoki, Jared. B Smith, Masakazu Igarashi, Patrice Coulon, Jeffery R. Wickens, Xin Jin, Tom J.H. Ruigrok.
  • Organizer: Society for Neuroscience 2018
  • Int'l Joint Research
• [Presentation] Anatomical evidence that multiple striatal regions influence motor cortex. (2017)
  • Author(s): Sho Aoki, Masakazu Igarashi, Patrice Coulon, Jeffery R. Wickens, Tom J.H. Ruigrok
  • Organizer: Society for Neuroscience 2017
  • Int'l Joint Research
• [Presentation] Anatomical evidence that multiple striatal regions influence motor cortex in the rat. (2017)
  • Author(s): Sho Aoki, Masakazu Igarashi, Patrice Coulon, Jeffery R. Wickens, Tom J.H. Ruigrok
  • Organizer: Procedural Learning Summer School
  • Int'l Joint Research