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

Research Project

Project/Area Number 19KK0192
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 46:Neuroscience and related fields
Research InstitutionKyoto 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, 特定教授 (80214196)
Project Period (FY) 2019-10-07 – 2023-03-31
Project Status Discontinued (Fiscal Year 2021)
Budget Amount *help
¥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

本研究においては、生体脳でのMRIを用いた生理学的結合関係の解析とトレーサー染色による解剖学的結合の3次元構築をt同一個体で重ね合わせて、相互の関係を解析するパイプラインを、最初はマーモセット、そして次にマカクザルで構築することを目的としている。令和3年度の研究の進捗としては、前年までに研究でマカクザルを対象とする高解像度のBOLD MRI画像取得のために、共同研究者のKU LeuvenのVanduffel研究室で構築されてきた頭蓋骨周囲に直接埋め込むimplantable coilをさらに改良し、異なる個体で共用できるような頭部近接装着型のコイルを作成し、京都大学の3T MRI機を用いて、高い空間解像度でのBOLD画像の取得に成功したコイルについて、京都大学の7T MRI機で使用した。構造画像については問題なく取得できたがBOLD画像についてはよりチューンアップが必要であることが判明した。
一方、組織標本の3-D再構築パイプラインの樹立については、脳幹における空間的注意の制御中枢である中脳上丘に逆行性の蛍光色素を注入した2頭のマーモセット個体について、蛍光標識された大脳皮質皮質ー上丘経路の再構築を行うことについて、Cold Spring Harbor研究所のMitra博士の研究室と共同して、自動的に逆行性標識細胞を同定し、領域ごとにその数を算出し、さらに全脳的に3次元再構築するシステムをほぼ確立することができた。その過程で、マウスとマーモセットの間で皮質-上丘投射系の構造に顕著な違いが観察されており、空間的注意を制御する皮質ー皮質下回路の進化について興味深い洞察が得られつつある。

Current Status of Research Progress
Current Status of Research Progress

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

Reason

現在、コロナウィルス感染拡大のため、国を超えた往来が不可能になっているが、隔週で米国Cold Spring Harbor研究所のグループと京都大学のグループでZOOM会議を行っており、進捗を確認しており、最近マーモセット脳の全脳回路レベルでの標識ニューロンの再構築法について大きな進展が見られた。

Strategy for Future Research Activity

今後マーモセット及びマウスについて皮質-上丘投射系の種間比較を行った論文を作成、投稿する予定である。さらに上丘の異なる空間位置を符号化する部位に投射する皮質ニューロンの分布も明らかにし、空間的注意を制御する皮質ー皮質下ネットワークの全容を明らかにしたい。

Report

(3 results)
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report

Research Products

(39 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (8 results) Journal Article (15 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 14 results,  Open Access: 10 results) Presentation (9 results) (of which Int'l Joint Research: 4 results,  Invited: 8 results) Remarks (7 results)

  • [Int'l Joint Research] Cold Spring Harbour Laboratory(米国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] ルーバンカトリック大学(ベルギー)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Katholic University Leuven(ベルギー)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Cold Spring Harbor研究所(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Pittsburgh大学(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] IIT Madras(インド)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Katholic University Leuven(ベルギー)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] Cold Spring Harbour Laboratory(米国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Amygdala Underlies the Environment Dependency of Defense Responses Induced via Superior Colliculus2022

    • 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

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Double viral vector intersectional approaches for pathway-selective manipulation of motor functions and compensatory mechanisms2022

    • Author(s)
      Isa Tadashi
    • Journal Title

      Experimental Neurology

      Volume: 349 Pages: 113959-113959

    • DOI

      10.1016/j.expneurol.2021.113959

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of Light Isoflurane Anesthesia on Organization of Direction and Orientation Selectivity in the Superficial Layer of the Mouse Superior Colliculus2022

    • Author(s)
      Masatoshi KASAI, Tadash ISA
    • Journal Title

      The Journal of Neuroscience

      Volume: 42 Pages: 619-630

    • DOI

      10.1523/jneurosci.1196-21.2021

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Visual instrumental learning in blindsight monkeys2021

    • Author(s)
      Kato Rikako、Zeghbib Abdelhafid、Redgrave Peter、Isa Tadashi
    • Journal Title

      Scientific Reports

      Volume: 11 Pages: 14819-14819

    • DOI

      10.1038/s41598-021-94192-7

    • NAID

      120007147049

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neural Mechanism of Blindsight in a Macaque Model2021

    • Author(s)
      Isa Tadashi、Yoshida Masatoshi
    • Journal Title

      Neuroscience

      Volume: 469 Pages: 138-161

    • DOI

      10.1016/j.neuroscience.2021.06.022

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The tectum/superior colliculus as the vertebrate solution for spatial sensory integration and action2021

    • Author(s)
      Isa Tadashi、Marquez-Legorreta Emmanuel、Grillner Sten、Scott Ethan K.
    • Journal Title

      Current Biology

      Volume: 31

    • DOI

      10.1016/j.cub.2021.04.001

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Divergent Whole Brain Projections from the Ventral Midbrain in Macaques2021

    • Author(s)
      Zubair Muhammad、Murris Sjoerd R、Isa Kaoru、Onoe Hirotaka、Koshimizu Yoshinori、Kobayashi Kenta、Vanduffel Wim、Isa Tadashi
    • Journal Title

      Cerebral Cortex

      Volume: online ahead of print Pages: 2913-2931

    • DOI

      10.1093/cercor/bhaa399

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • 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 safety2021

    • Author(s)
      Koshimizu Yoshinori、Isa Kaoru、Kobayashi Kenta、Isa Tadashi
    • Journal Title

      Gene Therapy

      Volume: online ahead of print Pages: 339-350

    • DOI

      10.1038/s41434-020-00212-y

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Selective Mesoaccumbal Pathway Inactivation Affects Motivation but Not Reinforcement-Based Learning in Macaques2020

    • Author(s)
      Vancraeyenest Pascaline、Arsenault John T.、Li Xiaolian、Zhu Qi、Kobayashi Kenta、Isa Kaoru、Isa Tadashi、Vanduffel Wim
    • Journal Title

      Neuron

      Volume: 108 Pages: 568-581

    • DOI

      10.1016/j.neuron.2020.07.013

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The Ventral Striatum is a Key Node for Functional Recovery of Finger Dexterity After Spinal Cord Injury in Monkeys2020

    • 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 Pages: 3259-3270

    • DOI

      10.1093/cercor/bhz307

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dexterous Hand Movements and Their Recovery After Central Nervous System Injury2019

    • Author(s)
      Isa Tadashi
    • Journal Title

      Annual review of neuroscience

      Volume: 42 Pages: 315-335

    • DOI

      10.1146/annurev-neuro-070918-050436

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Neuronal and microglial localization of secreted phosphoprotein 1 (osteopontin) in intact and damaged motor cortex of macaques2019

    • 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

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] The somatosensory cortex receives information about motor output2019

    • Author(s)
      Umeda Tatsuya、Isa Tadashi、Nishimura Yukio
    • Journal Title

      Science Advances

      Volume: 5 Pages: 5388-5388

    • DOI

      10.1126/sciadv.aaw5388

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dynamic Interaction between Cortico-Brainstem Pathways during Training-Induced Recovery in Stroke Model Rats2019

    • Author(s)
      Ishida A, Kobayashi K, Ueda Y, Shimizu T, Tajiri N, Isa T, Hida H
    • Journal Title

      Journal of Neuroscience

      Volume: 39 Pages: 7306-20

    • DOI

      10.1523/jneurosci.0649-19.2019

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Difference in context-dependency between orienting and defense-like responses induced by the superior colliculus2019

    • 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

    • Related Report
      2019 Research-status Report
    • Open Access / Int'l Joint Research
  • [Presentation] Dynamics of global brain networks for recovery from spinal cord injury2022

    • Author(s)
      Tadashi Isa
    • Organizer
      The 7th CiNet Conference: New horizons in brain mapping
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Induction of large-scaled adult brain plasticity for neuronal repair2022

    • Author(s)
      Tadashi Isa
    • Organizer
      The 25th Thai Neuroscience Society Conference 2022 (TNS25)
    • Related Report
      2021 Research-status Report
    • 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
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] How the brain works for recovery from spinal cord injury2021

    • Author(s)
      Tadashi Isa
    • Organizer
      Mongolian Neuroscience Society Meeting
    • Related Report
      2021 Research-status Report
    • 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"
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Activity of frontal network for performance of forced-choice manual response task in blindsight monkey2019

    • Author(s)
      Yusuke Yamamoto, Reona Yamaguchi, Tomohiko Takei, Zenas C. Chao, Tadashi Isa
    • Organizer
      Annual Meeting for the Society for Neuroscience
    • Related Report
      2019 Research-status Report
    • 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
    • Related Report
      2019 Research-status Report
    • 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
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Cortical oscillatory network for recovery from spinal cord injury2019

    • Author(s)
      Tadashi Isa
    • Organizer
      International Symposium on Neural Oscillation 2019
    • Related Report
      2019 Research-status Report
    • 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/

    • Related Report
      2021 Research-status Report 2020 Research-status Report
  • [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/

    • Related Report
      2021 Research-status Report 2020 Research-status Report
  • [Remarks] researchmap 伊佐 正

    • Related Report
      2021 Research-status Report
  • [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/

    • Related Report
      2021 Research-status Report
  • [Remarks] researchmap 伊佐 正

    • URL

      https://researchmap.jp/tadashiisa/?lang=japanese

    • Related Report
      2020 Research-status Report
  • [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/

    • Related Report
      2020 Research-status Report
  • [Remarks] 脳・脊髄損傷からの機能回復機構

    • URL

      https://nscinbiol.med.kyoto-u.ac.jp/projects/

    • Related Report
      2019 Research-status Report

URL: 

Published: 2019-10-10   Modified: 2022-12-28  

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