Chemogenetic dissection of the primate prefronto-subcortical pathways for adaptive behavior

• Project/Area Number: 18K15353
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51020:Cognitive and brain science-related
• Research Institution: National Institutes for Quantum Science and Technology
• Principal Investigator: Oyama Kei 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, 研究員 (50615250)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 霊長類 / 化学遺伝学 / 前頭前野 / 大脳基底核 / 視床 / 前頭連合野 / 経路選択的機能阻害 / 線条体 / 前頭眼窩野 / 経路選択的阻害 / 報酬 / 意思決定

Outline of Final Research Achievements

In this study, we investigated the functional roles of orbitofrontal cortex and its projections to subcortical structures in adaptive behavior. We found that the pathway from the OFC to the caudate nuclues is involved in value updating in a model-free manner, and the pathway from the OFC to the mediodorsal thalamus in rule shift in a model-based manner. These results suggest that projections from OFC to subcortical structures play different roles in adaptive behavior.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は霊長類前頭前野を中心とした神経経路の機能的役割を明らかにした基礎脳科学的成果に加え、霊長類脳機能を探索する上での新奇な方法論の確立、および当該神経経路の破綻が原因と目されている精神疾患の治療法の確立に向けて重要な知見を提供した。

Research Products

• [Journal Article] Chronic Behavioral Manipulation via Orally Delivered Chemogenetic Actuator in Macaques (2022)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Chemogenetic dissection of the primate prefronto-subcortical pathways for working memory and decision-making (2021)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Deschloroclozapine, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys (2020)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Signaling Incentive and Drive in the Primate Ventral Pallidum for Motivational Control of Goal-Directed Action (2019)
  • 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
  • Peer Reviewed / Open Access
• [Presentation] dissection of the primate prefronto-subcortical pathways for higher-order functions (2021)
  • Author(s): Kei Oyama
  • Organizer: 第44回日本神経科学大会
  • Int'l Joint Research
• [Presentation] DREADDを用いた経路選択的阻害法による、サル前頭前野と視床MD核及び線条体を結ぶ神経経路のワーキングメモリにおける役割の解明 (2020)
  • Author(s): Kei Oyama, Yukiko Hori, Yuji Nagai, Naohisa Miyakawa, Koki Mimura, Toshiyuki Hirabayashi, Ken-ichi Inoue, Masahiko Takada, Makoto Higuchi, Takafumi Minamimoto
  • Organizer: 第43回日本神経科学大会
  • Int'l Joint Research
• [Presentation] DREADDによる、報酬を基にした柔軟な意思決定におけるサル前頭眼窩野とその皮質下領域への経路の役割の解明 (2019)
  • Author(s): Kei Oyam小山 佳, 堀 由紀子, 永井 裕司, 平林 敏行, 宮川 尚久, 藤本 淳, 三村 喬生, 井上 謙一, Mark A.G. Eldridge, Richard C Saunders, 須原 哲也, 高田 昌彦, 樋口 真人, Barry J. Richmond, 南本 敬史
  • Organizer: 日本神経科学学会
  • Int'l Joint Research