Elucidation of the neural mechanism for Shitsukan-value translations

• Project Area: Analysis and synthesis of deep SHITSUKAN information in the real world
• Project/Area Number: 20H05955
• Research Category: Grant-in-Aid for Transformative Research Areas (A)
• Allocation Type: Single-year Grants
• Review Section: Transformative Research Areas, Section (IV)
• Research Institution: National Institutes for Quantum Science and Technology
• Principal Investigator: 南本 敬史 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センター, 次長 (50506813)
• Co-Investigator(Kenkyū-buntansha): 小松 英彦 玉川大学, 脳科学研究所, 研究員 (00153669) ; 網田 英敏 京都大学, ヒト行動進化研究センター, 特定助教 (80845321) ; 村田 航志 福井大学, 学術研究院医学系部門, 助教 (10631913)
• Project Period (FY): 2020-11-19 – 2025-03-31
• Project Status: Granted (Fiscal Year 2024)
• Budget Amount: ¥134,030,000 (Direct Cost: ¥103,100,000、Indirect Cost: ¥30,930,000); Fiscal Year 2024: ¥22,100,000 (Direct Cost: ¥17,000,000、Indirect Cost: ¥5,100,000); Fiscal Year 2023: ¥22,100,000 (Direct Cost: ¥17,000,000、Indirect Cost: ¥5,100,000); Fiscal Year 2022: ¥22,100,000 (Direct Cost: ¥17,000,000、Indirect Cost: ¥5,100,000); Fiscal Year 2021: ¥20,930,000 (Direct Cost: ¥16,100,000、Indirect Cost: ¥4,830,000); Fiscal Year 2020: ¥46,800,000 (Direct Cost: ¥36,000,000、Indirect Cost: ¥10,800,000)
• Keywords: 質感 / 価値 / 好み / サル / 神経活動操作 / 神経活動操作技術

Outline of Research at the Start

私たちは多様な感覚情報を評価するにあたって、生物的な欲求、学習・経験、環境、文脈、感情などによる影響をうける。本研究は、この深奥質感認知のコアをなす生態学的価値計算とその変調の仕組みの理解を目指す。そのために高次感覚野と複数の価値変調システムと相互作用による生態学的価値計算処理について、質感や価値に関する神経情報の計測や解読に加え、神経活動を制御することで脳情報処理の相関・因果をあわせて解析する。

Outline of Annual Research Achievements

（1）価値システムと高次感覚野との相互作用による質感－価値変換の並列処理機構の解明：マカクザルを対象として生物学的価値システムの一つである前頭眼窩野やそこから投射する神経経路を化学遺伝学的に抑制する複数の実験結果により、意欲制御（内的欲求の変化に伴う価値判断）、経験・推論に基づく行動、情動音声に対する反応、視覚記憶、のそれぞれの機能に関与する神経ネットワークとその作動原理の理解が進んだ。また、サル用の仮想現実（VR）システムの開発とその利用をすすめ、環境の複雑さと探索行動との関連について定量解析できる可能性を見出した。またサルの下側頭皮質と第一次視覚野のニューロン活動の解析を進め、物体表面属性の形成に重要な役割を果たす充填の過程に第一次視覚野へのフィードバック信号が関係する可能性を見出した。（２）価値システム間をつなぐ神経ネットワークとモノアミン系の作動による価値統合・変調処理の解明：セロトニン受容体の4つのサブタイプの脳内分布と視覚刺激に基づく価値判断課題における役割について調べ、内側前頭葉や扁桃体においてセロトニンが5HT1A受容体を介してコスト感受性を制御している可能性を見出した。また逆行性ウイルスベクターを用いて線条体に投射するドーパミン細胞を標識した。その結果、投射先の違いによってドーパミン細胞のカルビンディン発現レベルに違いがあることを見つけた。この成果は、パーキンソン病患者における価値判断の変容を解明する手がかりとなりうる。さらに、ラット味覚反応試験を用いた行動薬理学実験により、腹側線条体領域（嗅結節）において快反応形成に関わる局所領域を探査し、嗅結節の前内側部が快反応形成に関わることを見出した。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

特に、前頭眼窩野の機能と他の脳領域との相互作用についての知見が蓄積されるなど、視覚と価値の変換メカニズムの理解が深まった。また、サルVRシステムの開発が進み、質感と価値の関係に新たな理解が得られる道筋を示した。ドーパミン信号計測については、2頭のサルで成功し、脳内に蛍光ドーパミンセンサーが発現していることを確認できたため、これまでに行ったドーパミンの価値変調システムにかかわる研究結果を裏付けることができた。

Strategy for Future Research Activity

領域の終了に向けて、これまでの成果を取りまとめる。開発したサルVRシステムの応用研究を進め具体的な成果として示せるように取り組む。これまでに行ってきたサル線条体におけるドーパミン信号計測の研究成果を論文化する。

Research Products

• [Int'l Joint Research] NIH(米国)
• [Int'l Joint Research] NIMH/NIH(米国)
• [Int'l Joint Research] ICM/CNRS(フランス)
• [Int'l Joint Research] NIH(米国)
• [Journal Article] Reduced serotonergic transmission alters sensitivity to cost and reward via 5-HT1A and 5-HT1B receptors in monkeys (2024)
  • Author(s): Hori Yukiko、Mimura Koki、Nagai Yuji、Hori Yuki、Kumata Katsushi、Zhang Ming-Rong、Suhara Tetsuya、Higuchi Makoto、Minamimoto Takafumi
  • Journal Title: PLOS Biology Volume: 22 Issue: 1 Pages: 1-25
  • DOI: 10.1371/journal.pbio.3002445
  • Peer Reviewed / Open Access
• [Journal Article] An intra-oral flavor detection task in freely moving mice (2024)
  • Author(s): Shiotani Kazuki、Tanisumi Yuta、Osako Yuma、Murata Koshi、Hirokawa Junya、Sakurai Yoshio、Manabe Hiroyuki
  • Journal Title: iScience Volume: 27 Issue: 2 Pages: 108924-108924
  • DOI: 10.1016/j.isci.2024.108924
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Enhancement of Haloperidol-Induced Catalepsy by GPR143, an L-Dopa Receptor, in Striatal Cholinergic Interneurons (2024)
  • Author(s): Arai Masami、... 、Kambe Yuki、... 、Goshima Yoshio
  • Journal Title: The Journal of Neuroscience Volume: 44 Issue: 11 Pages: 1504-1523
  • DOI: 10.1523/jneurosci.1504-23.2024
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Stable Neural Population Dynamics in the Regression Subspace for Continuous and Categorical Task Parameters in Monkeys (2023)
  • Author(s): Chen He、Kunimatsu Jun、Oya Tomomichi、Imaizumi Yuri、Hori Yukiko、Matsumoto Masayuki、Minamimoto Takafumi、Naya Yuji、Yamada Hiroshi
  • Journal Title: eneuro Volume: 10 Issue: 7 Pages: 16-23
  • DOI: 10.1523/eneuro.0016-23.2023
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A mosaic adeno-associated virus vector as a versatile tool that exhibits high levels of transgene expression and neuron specificity in primate brain. (2023)
  • Author(s): Kimura K; Nagai Y; Hatanaka G; Fang Y; Tanabe S; Zheng A; Fujiwara M; Nakano M; Hori Y; Takeuchi RF; Inagaki M; Minamimoto T; Fujita I; Inoue K; Takada M
  • Journal Title: Nature Communications Volume: 14 Issue: 1 Pages: 4762-4762
  • DOI: 10.1038/s41467-023-40436-1
  • Peer Reviewed / Open Access
• [Journal Article] Multimodal imaging for validation and optimization of ion channel-based chemogenetics in nonhuman primates (2023)
  • Author(s): Yuki Hori, Yuji Nagai, Yukiko Hori, Kei Oyama, Koki Mimura, Toshiyuki Hirabayashi, Ken-ichi Inoue, Masayuki Fujinaga, Ming-Rong Zhang, Masahiko Takada, Makoto Higuchi, Takafumi Minamimoto
  • Journal Title: Journal of Neuroscience Volume: 43 Issue: 39 Pages: 6619-6627
  • DOI: 10.1523/jneurosci.0625-23.2023
  • Peer Reviewed / Open Access
• [Journal Article] Targeted Delivery of Chemogenetic Adeno-Associated Viral Vectors to Cortical Sulcus Regions in Macaque Monkeys by Handheld Injections (2023)
  • Author(s): Oyama Kei、Nagai Yuji、Minamimoto Takafumi
  • Journal Title: BIO-PROTOCOL Volume: 13 Issue: 23
  • DOI: 10.21769/bioprotoc.4897
  • Peer Reviewed / Open Access
• [Journal Article] Chemogenetics for cell-type-specific modulation of signalling and neuronal activity (2023)
  • Author(s): Kang Hye Jin、Minamimoto Takafumi、Wess J?rgen、Roth Bryan L.
  • Journal Title: Nature Reviews Methods Primers Volume: 3 Issue: 1
  • DOI: 10.1038/s43586-023-00276-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Local field potential responses associated with perceptual filling-in at blind spot in macaque primary visual cortex (2023)
  • Author(s): Saito Harumi、Masaoka Akihiro、Komatsu Hidehiko
  • Journal Title: Journal of Neurophysiology Volume: 130 Issue: 6 Pages: 1464-1479
  • DOI: 10.1152/jn.00281.2023
  • Peer Reviewed
• [Journal Article] Neural mechanisms of olfaction and motivation for eating (2023)
  • Author(s): 村田 航志
  • Journal Title: The Japanese Journal of Taste and Smell Research Volume: 30 Issue: 1 Pages: 29-35
  • DOI: 10.18965/tasteandsmell.30.1_29
  • ISSN: 1340-4806, 2424-1326
  • Peer Reviewed
• [Journal Article] Neuronal mechanisms underlying face recognition in non-human primates (2023)
  • Author(s): Amita H*, Koyano KW, Kunimatsu J.
  • Journal Title: Japanese Psychological Research Volume: -
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Chemogenetic attenuation of cortical seizures in nonhuman primates (2023)
  • Author(s): Miyakawa Naohisa、Nagai Yuji、Hori Yukiko、Mimura Koki、Orihara Asumi、Oyama Kei、Matsuo Takeshi、Inoue Ken-ichi、Suzuki Takafumi、Hirabayashi Toshiyuki、Suhara Tetsuya、Takada Masahiko、Higuchi Makoto、Kawasaki Keisuke、Minamimoto Takafumi
  • Journal Title: Nature Communications Volume: 14 Issue: 1 Pages: 1-11
  • DOI: 10.1038/s41467-023-36642-6
  • Peer Reviewed / Open Access
• [Journal Article] Chemogenetic Disconnection between the Orbitofrontal Cortex and the Rostromedial Caudate Nucleus Disrupts Motivational Control of Goal-Directed Action (2022)
  • Author(s): Oyama Kei、Hori Yukiko、Mimura Koki、Nagai Yuji、Eldridge Mark A. G.、Saunders Richard C.、Miyakawa Naohisa、Hirabayashi Toshiyuki、Hori Yuki、Inoue Ken-ichi、Suhara Tetsuya、Takada Masahiko、Higuchi Makoto、Richmond Barry J.、Minamimoto Takafumi
  • Journal Title: The Journal of Neuroscience Volume: 42 Issue: 32 Pages: 6267-6275
  • DOI: 10.1523/jneurosci.0229-22.2022
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Origin of the ease of association of color names: Comparison between humans and AI (2022)
  • Author(s): Komatsu Hidehiko、Maeno Ami、Watanabe Eiji
  • Journal Title: i-Perception Volume: 13 Issue: 5
  • DOI: 10.1177/20416695221131832
  • 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
  • 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
  • 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 monkeys (2021)
  • 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
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Structure and function of neural circuit related to gloss perception in the macaque inferior temporal cortex: a case report (2021)
  • Author(s): Komatsu Hidehiko、Nishio Akiko、Ichinohe Noritaka、Goda Naokazu
  • Journal Title: Brain Structure and Function Volume: 226 Issue: 9 Pages: 3023-3030
  • DOI: 10.1007/s00429-021-02324-6
  • Peer Reviewed / Open Access
• [Journal Article] Relationship between the activities of gloss-selective neurons in the macaque inferior temporal cortex and the gloss discrimination behavior of the monkey (2021)
  • Author(s): Baba M, Nishio A, Komatsu H
  • Journal Title: Cerebral Cortex Communications Volume: 2 Issue: 1 Pages: 1-13
  • DOI: 10.1093/texcom/tgab011
  • Peer Reviewed / Open Access
• [Presentation] Imaging-Guided Chemogenetics: A Window into Nonhuman Primate Brain Circuts and Functions. (2023)
  • Author(s): Minamimoto T.
  • Organizer: OHBM
  • Int'l Joint Research / Invited
• [Presentation] ヒト-非ヒト霊長類比較研究ー化学遺伝学を用いた双方向的アプローチ (2023)
  • Author(s): Minamimoto T.
  • Organizer: 第46回日本神経科学大会シンポジウム「神経科学研究の動向と今後の発展の方向性」
  • Int'l Joint Research / Invited
• [Presentation] A fluorescent dopamine sensor reveals distinct signals on reward prediction error and expected reward value in the primate putamen and caudate nucleus (2023)
  • Author(s): Yan G., Amita H., Nonomura S., Inoue K., Takada M.
  • Organizer: XIVth Meeting for International Basal Ganglia Society
  • Int'l Joint Research / Invited
• [Presentation] Local field potential (LFP) oscillations associated with perceptual filling-in at the blind spot in macaque primary visual cortex (2023)
  • Author(s): Saito H, Masaoka A, Komatsu H
  • Organizer: 第46回日本神経科学大会, 神戸
  • Int'l Joint Research / Invited
• [Presentation] Identification of subtypes of ultrasonic vocalizations associated with chocolate eating in rats using machine learning (2023)
  • Author(s): Murata K, Ikedo Y, Ryoke T, Shiotani K, Manabe H, Kuroda K, Yoshimura H, and Fukazawa Y
  • Organizer: Neuroscience 2023 (Society for Neuroscience)
  • Int'l Joint Research / Invited
• [Presentation] ドーパミン蛍光イメージング技術の霊長類脳への適用 (2023)
  • Author(s): Amita H.
  • Organizer: 第４回サル脳新技術研究会
• [Presentation] メタコントラスト・マスキングにおける第一次視覚野ニューロン集団の動的特性 (2023)
  • Author(s): 正岡明浩、斉藤治美、小松英彦
  • Organizer: 第４回サル脳新技術研究会
• [Presentation] Visualizing and manipulating primate brain circuits and functions (2022)
  • Author(s): Minamimoto T.
  • Organizer: Neuro2022
  • Int'l Joint Research / Invited
• [Presentation] Imaging-guided chemogenetics reveals dissociable roles of primate prefronto-subcortical pathways for cognitive functions (2022)
  • Author(s): Minamimoto T.
  • Organizer: Viral Manipulation on Monkeys Conference, Paris
  • Int'l Joint Research / Invited
• [Presentation] Chemogenetic dissection of the primate prefronto-subcortical pathways for cognitive functions (2022)
  • Author(s): Minamimoto T.
  • Organizer: CNS-JNS symposium, Chinese Neuroscience Society 2022
  • Int'l Joint Research / Invited
• [Presentation] Imaging-guided chemogenetics for nonhuman primates (2022)
  • Author(s): Minamimoto T.
  • Organizer: Genetic technologies for systems neuroscience in non-human primates, NIMH, Bethesda
  • Int'l Joint Research / Invited
• [Presentation] Imaging guided chemogenetics: Visualization and manipulation of non-human primate brain circuits and functions (2022)
  • Author(s): Minamimoto T.
  • Organizer: Multi-disciplinary approach to understand neuronal network architecture to control motor actions, NIPS
  • Int'l Joint Research / Invited
• [Presentation] Multiple functional dopamine-basal ganglia circuits in primates (2022)
  • Author(s): Amita H.
  • Organizer: Japan and Norway United in Brain, Educations and Therapeutics Symposium
  • Int'l Joint Research
• [Presentation] Distinct patterns of dopamine responses to reward association in primate caudate nucleus and putamen as revealed by dLight signals (2022)
  • Author(s): Gaoge Y., Amita H., Nonomura S., Inoue K., Takada M.
  • Organizer: Neuroscience 2022 (Society for Neuroscience)
  • Int'l Joint Research
• [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
  • Invited
• [Presentation] Visualizing and manipulating primate brain circuits with DREADDs (2022)
  • Author(s): Minamimoto T.
  • Organizer: 7th CiNet Conference
  • 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
  • Invited
• [Presentation] Neural mechanism for valuation and motivation in health and disease (2021)
  • Author(s): Minamimoto T, Hori Y, Oyama K
  • Organizer: 第44回日本神経科学大会, 神戸
  • Int'l Joint Research / Invited
• [Presentation] Interrogation of monkey brain circuits with imaging-guided chemogenetics (2021)
  • Author(s): Minamimoto T
  • Organizer: ASPET 2021, American Society for Pharmacology and Experimental Therapeutics
  • Int'l Joint Research / Invited
• [Presentation] The role of perineuronal nets in the substantia nigra pars lateralis in object skill learning (2021)
  • Author(s): Amita H., Takayasu T., Yan G., Hikosaka O., Takada M.
  • Organizer: 第44回日本神経科学大会/CJK 第1回国際会議
  • Int'l Joint Research / Invited
• [Presentation] Neural mechanisms of motivational control based on cost-benefit comparison in monkey (2020)
  • Author(s): 南本 敬史
  • Organizer: 第９８回日本生理学会大会シンポジウム
  • Invited
• [Presentation] Dopamine, Serotonin, and Motivation (2020)
  • Author(s): 南本 敬史
  • Organizer: 京都大学霊長類研究所 共同利用研究会
  • Invited
• [Presentation] The role of the substantia nigra pars lateralis in object skill learning (2020)
  • Author(s): 網田 英敏
  • Organizer: 第10回 生理研―霊長研―新潟脳研 合同シンポジウム
  • Invited
• [Presentation] 質感知覚の神経機構を探る (2020)
  • Author(s): 小松 英彦
  • Organizer: 電子情報通信学会NC研究会
  • Invited
• [Book] Annual Review神経 2023 (2023)
  • Author(s): 南本敬史
  • Total Pages: 340
  • Publisher: 中外医学社
  • ISBN: 9784498428003
• [Book] 霊長類の百科事典 (2023)
  • Author(s): 小松英彦
  • Total Pages: 752
  • Publisher: 丸善出版
  • ISBN: 9784621308042
• [Book] 視能訓練学 第2版 (2023)
  • Author(s): 小松英彦 （共著）
  • Total Pages: 452
  • Publisher: 医学書院
• [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
• [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
• [Remarks] 深奥質感領域HP
  • URL: https://shitsukan.jp/deep/