Establishing the pipeline for 3D reconstruction of neurophysiological and anatomical maps of the nonhuman primate brain

• Project/Area Number: 19KK0192
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 46:Neuroscience and related fields
• Research Institution: Kyoto University
• Principal Investigator: 伊佐 正 京都大学, 医学研究科, 教授 (20212805)
• Co-Investigator(Kenkyū-buntansha): 岡田 知久 京都大学, 医学研究科, 准教授 (30321607) ; 山口 玲欧奈 京都大学, 高等研究院, 特定助教 (50812640) ; 尾上 浩隆 京都大学, 医学研究科, 研究員 (80214196)
• Project Period (FY): 2019-10-07 – 2023-03-31
• Project Status: Discontinued (Fiscal Year 2022)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2022: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2021: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
• Keywords: 機能的MRI / 全脳神経回路 / 三次元再構築 / マーモセット / マカクザル / 機能的結合 / 解剖学的結合 / 脳機能画像 / 高次脳機能 / 霊長類

Outline of Research at the Start

脳による行動の制御や意思決定に関わる大規模な回路機構を理解するために、代表申請者の伊佐が、米国Cold Spring Harbor研究所のPartha Mitra及びベルギーのLeuven Katholic大学のWim Vanduffelらのグループと共同し、機能的MRIによって得られる（１）安静時結合マップ及び（２）光刺激の効果マップと、Mitraらが開発した（３）全脳レベルでの解剖学的結合マップとを同一個体で重ね合わせる手法を開発する。最初の2年はマーモセットで解剖学的結合マップの構築を完成させ、２年目の途中からマカクザルを対象として生理学的マップとか解剖学的マップの重ね合わせパイプラインを構築する。

Outline of Annual Research Achievements

本研究課題においては、霊長類の脳を対象とし、領域間の解剖学的結合関係と機能的MRIなどによって計測される生理的な機能連関がどのような関係にあるのかを明らかにすることを目的とした。そのために、（１）神経トレーサーによる神経経路を可視化したデータを三次元再構築するパイプラインの構築と、（２）脳の機能的ネットワークを機能的MRIによって解析し、それらを同一個体において関連する領域の解剖学的結合関係を対比させながら解析するパイプラインを構築する、ことを目指した。
（１）については、マーモセット脳において、中脳上丘の異なる空間表現部位（吻側は中心視野、尾側は周辺視野）に逆行性ウィルストレーサーを注入し、逆行性に標識される皮質細胞の分布を三次元再構築するパイプラインをCold Spring Harbour研究所のPartha Mitra博士とともに、構築を試みた。令和４年度春の時点では、三次元再構築するためのパイプラインは完成し、軸索走行を自動的にトレースするシステムはほぼ完成したが、逆行性標識細胞の検出においては、一部軸索を細胞体と間違えることがあり、より高精度化に向けたてシステム改良中である。一方（２）については、ベルギーのKUリューベンのVanduffel教授と共同し、同グループで開発された、マカクザルの頭蓋骨密着型のMRI用コイルを改造して京都大学の７TのMRI機での使用が可能な特製のコイルを開発し、サルの７T機での安静時結合の解析に成功した。特に両側の運動前野間の結合に関心を持っており、そのウィルストレーサーを用いた経路の選択的遮断とその解剖学的標識にも成功した。これにより、解剖学的結合と安静時MRIによる機能的結合の関係を解析、さらに選択的遮断した時の効果を解析できるところまできた。しかし、令和４年度に基盤Sを獲得したことで、本プロジェクトは別プロジェクトで継続の予定である。

Research Products

• [Int'l Joint Research] Cold Spring Harbour laboratory(米国)
• [Int'l Joint Research] Katholic University Leuven(ベルギー)
• [Int'l Joint Research] Cold Spring Harbour Laboratory(米国)
• [Int'l Joint Research] ルーバンカトリック大学(ベルギー)
• [Int'l Joint Research] Katholic University Leuven(ベルギー)
• [Int'l Joint Research] Cold Spring Harbor研究所(米国)
• [Int'l Joint Research] Pittsburgh大学(米国)
• [Int'l Joint Research] IIT Madras(インド)
• [Int'l Joint Research] Katholic University Leuven(ベルギー)
• [Int'l Joint Research] Cold Spring Harbour Laboratory(米国)
• [Journal Article] Phylogenetic view of the compensatory mechanisms in motor and sensory systems after neuronal injury (2022)
  • Author(s): Isa Tadashi、Tohyama Takamichi、Kinoshita Masaharu
  • Journal Title: Current Research in Neurobiology Volume: 3 Pages: 100058-100058
  • DOI: 10.1016/j.crneur.2022.100058
  • Peer Reviewed / Open Access
• [Journal Article] A multisynaptic pathway from the ventral midbrain toward spinal motoneurons in monkeys (2022)
  • Author(s): Suzuki Michiaki、Inoue Ken‐ichi、Nakagawa Hiroshi、Ishida Hiroaki、Kobayashi Kenta、Isa Tadashi、Takada Masahiko、Nishimura Yukio
  • Journal Title: The Journal of Physiology Volume: 600 Issue: 7 Pages: 1731-1752
  • DOI: 10.1113/jp282429
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Amygdala Underlies the Environment Dependency of Defense Responses Induced via Superior Colliculus (2022)
  • Author(s): Isa Kaoru、Tokuoka Kota、Ikeda Sakura、Karimi Sara、Kobayashi Kenta、Sooksawate Thongchai、Isa Tadashi
  • Journal Title: Frontiers in Neural Circuits Volume: 15 Pages: 768647-768647
  • DOI: 10.3389/fncir.2021.768647
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Double viral vector intersectional approaches for pathway-selective manipulation of motor functions and compensatory mechanisms (2022)
  • Author(s): Isa Tadashi
  • Journal Title: Experimental Neurology Volume: 349 Pages: 113959-113959
  • DOI: 10.1016/j.expneurol.2021.113959
  • Peer Reviewed
• [Journal Article] Effects of Light Isoflurane Anesthesia on Organization of Direction and Orientation Selectivity in the Superficial Layer of the Mouse Superior Colliculus (2022)
  • Author(s): Masatoshi KASAI, Tadash ISA
  • Journal Title: J Neurosci Volume: 42 Issue: 4 Pages: 619-630
  • DOI: 10.1523/jneurosci.1196-21.2021
  • Peer Reviewed / Open Access
• [Journal Article] Visual instrumental learning in blindsight monkeys (2021)
  • Author(s): Kato Rikako、Zeghbib Abdelhafid、Redgrave Peter、Isa Tadashi
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 14819-14819
  • DOI: 10.1038/s41598-021-94192-7
  • NAID: 120007147049
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neural Mechanism of Blindsight in a Macaque Model (2021)
  • Author(s): Isa Tadashi、Yoshida Masatoshi
  • Journal Title: Neuroscience Volume: 469 Pages: 138-161
  • DOI: 10.1016/j.neuroscience.2021.06.022
  • Peer Reviewed / Open Access
• [Journal Article] The tectum/superior colliculus as the vertebrate solution for spatial sensory integration and action (2021)
  • Author(s): Isa Tadashi、Marquez-Legorreta Emmanuel、Grillner Sten、Scott Ethan K.
  • Journal Title: Current Biology Volume: 31 Issue: 11 Pages: R741-R762
  • DOI: 10.1016/j.cub.2021.04.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Divergent Whole Brain Projections from the Ventral Midbrain in Macaques (2021)
  • Author(s): Zubair Muhammad、Murris Sjoerd R、Isa Kaoru、Onoe Hirotaka、Koshimizu Yoshinori、Kobayashi Kenta、Vanduffel Wim、Isa Tadashi
  • Journal Title: Cerebral Cortex Volume: 31 Issue: 6 Pages: 2913-2931
  • DOI: 10.1093/cercor/bhaa399
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Double viral vector technology for selective manipulation of neural pathways with higher level of efficiency and safety (2021)
  • Author(s): Koshimizu Yoshinori、Isa Kaoru、Kobayashi Kenta、Isa Tadashi
  • Journal Title: Gene Therapy Volume: online ahead of print Issue: 6 Pages: 339-350
  • DOI: 10.1038/s41434-020-00212-y
  • Peer Reviewed / Open Access
• [Journal Article] Selective Mesoaccumbal Pathway Inactivation Affects Motivation but Not Reinforcement-Based Learning in Macaques (2020)
  • Author(s): Vancraeyenest Pascaline、Arsenault John T.、Li Xiaolian、Zhu Qi、Kobayashi Kenta、Isa Kaoru、Isa Tadashi、Vanduffel Wim
  • Journal Title: Neuron Volume: 108 Issue: 3 Pages: 568-581
  • DOI: 10.1016/j.neuron.2020.07.013
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Dexterous Hand Movements and Their Recovery After Central Nervous System Injury (2019)
  • Author(s): Isa Tadashi
  • Journal Title: Annual Review of Neuroscience Volume: 42 Issue: 1 Pages: 315-335
  • DOI: 10.1146/annurev-neuro-070918-050436
  • Peer Reviewed
• [Journal Article] Neuronal and microglial localization of secreted phosphoprotein 1 (osteopontin) in intact and damaged motor cortex of macaques (2019)
  • Author(s): Sugiyama Yoko、Oishi Takao、Yamashita Akiko、Murata Yumi、Yamamoto Tatsuya、Takashima Ichiro、Isa Tadashi、Higo Noriyuki
  • Journal Title: Brain Research Volume: 1714 Pages: 52-64
  • DOI: 10.1016/j.brainres.2019.02.021
  • Peer Reviewed
• [Journal Article] The somatosensory cortex receives information about motor output (2019)
  • Author(s): Umeda Tatsuya、Isa Tadashi、Nishimura Yukio
  • Journal Title: Science Advances Volume: 5 Issue: 7 Pages: 5388-5388
  • DOI: 10.1126/sciadv.aaw5388
  • Peer Reviewed / Open Access
• [Journal Article] Dynamic Interaction between Cortico-Brainstem Pathways during Training-Induced Recovery in Stroke Model Rats (2019)
  • Author(s): Ishida A, Kobayashi K, Ueda Y, Shimizu T, Tajiri N, Isa T, Hida H
  • Journal Title: J Neurosci Volume: 39 Issue: 37 Pages: 7306-7320
  • DOI: 10.1523/jneurosci.0649-19.2019
  • Peer Reviewed / Open Access
• [Journal Article] The Ventral Striatum is a Key Node for Functional Recovery of Finger Dexterity After Spinal Cord Injury in Monkeys (2019)
  • Author(s): Suzuki Michiaki、Onoe Kayo、Sawada Masahiro、Takahashi Nobuaki、Higo Noriyuki、Murata Yumi、Tsukada Hideo、Isa Tadashi、Onoe Hirotaka、Nishimura Yukio
  • Journal Title: Cerebral Cortex Volume: 30 Issue: 5 Pages: 3259-3270
  • DOI: 10.1093/cercor/bhz307
  • Peer Reviewed / Open Access
• [Journal Article] Difference in context-dependency between orienting and defense-like responses induced by the superior colliculus (2019)
  • Author(s): Isa Kaoru、Sooksawate Thongchai、Kobayashi Kenta、Kobayashi Kazuto、Redgrave Peter、Isa Tadashi
  • Journal Title: bioRxiv Volume: 729772 Pages: 729772-729772
  • DOI: 10.1101/729772
  • Open Access / Int'l Joint Research
• [Presentation] Dynamics of global brain networks for recovery from spinal cord injury (2022)
  • Author(s): Tadashi Isa
  • Organizer: The 7th CiNet Conference: New horizons in brain mapping
  • Int'l Joint Research / Invited
• [Presentation] Induction of large-scaled adult brain plasticity for neuronal repair (2022)
  • Author(s): Tadashi Isa
  • Organizer: The 25th Thai Neuroscience Society Conference 2022 (TNS25)
  • Int'l Joint Research / Invited
• [Presentation] 盲視の脳内メカニズム -非ヒト科霊長類を用いた研究について- (2021)
  • Author(s): 伊佐 正
  • Organizer: 視覚科学フォーラム
  • Invited
• [Presentation] How the brain works for recovery from spinal cord injury (2021)
  • Author(s): Tadashi Isa
  • Organizer: Mongolian Neuroscience Society Meeting
  • Int'l Joint Research / Invited
• [Presentation] How does the non-conscious visuo-motor function emerge after damage to the primary motor cortex? (2020)
  • Author(s): Tadashi Isa
  • Organizer: 1st CU-KU Symposium and 4th CU-NIPS Symposium "Advances in Neuroscience Research"
  • Invited
• [Presentation] Activity of frontal network for performance of forced-choice manual response task in blindsight monkey (2019)
  • Author(s): Yusuke Yamamoto, Reona Yamaguchi, Tomohiko Takei, Zenas C. Chao, Tadashi Isa
  • Organizer: Annual Meeting for the Society for Neuroscience
  • Int'l Joint Research
• [Presentation] 基礎研究の魅力：日本神経科学学会会長から (2019)
  • Author(s): 伊佐 正
  • Organizer: 第６０回日本神経学会学術集会 シンポジウム
  • Invited
• [Presentation] 機能回復の脳科学 (2019)
  • Author(s): 伊佐 正
  • Organizer: 第3回全国在宅医療医歯薬連合会全国大会シンポジウム
  • Invited
• [Presentation] Cortical oscillatory network for recovery from spinal cord injury (2019)
  • Author(s): Tadashi Isa
  • Organizer: International Symposium on Neural Oscillation 2019
  • Invited
• [Remarks] 京都大学大学院医学研究科 高次脳科学講座 神経生物学分野
  • URL: https://nscinbiol.med.kyoto-u.ac.jp/
• [Remarks] 京都大学ヒト生物学高等研究拠点 伊佐グループ
  • URL: https://ashbi.kyoto-u.ac.jp/ja/groups/isa/
• [Remarks] researchmap 伊佐 正
• [Remarks] 京都大学大学院医学研究科・医学部 神経生物学
  • URL: https://www.med.kyoto-u.ac.jp/organization-staff/research/doctoral_course/r-019/
• [Remarks] researchmap 伊佐 正
  • URL: https://researchmap.jp/tadashiisa/?lang=japanese
• [Remarks] 京都大学医学研究科神経生物学分野
  • URL: https://www.med.kyoto-u.ac.jp/organization-staff/research/doctoral_course/r-019/
• [Remarks] 脳・脊髄損傷からの機能回復機構
  • URL: https://nscinbiol.med.kyoto-u.ac.jp/projects/