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2020 Fiscal Year Annual Research Report

Elucidation of the hyper-adaptation mechanism by reconstruction of bio-structure and challenges for prevention of decline in latent adaptive capacity

Planned Research

Project AreaHyper-adaptability for overcoming body-brain dysfunction: Integrated empirical and system theoretical approaches
Project/Area Number 19H05723
Research InstitutionKyoto University

Principal Investigator

伊佐 正  京都大学, 医学研究科, 教授 (20212805)

Co-Investigator(Kenkyū-buntansha) 内藤 栄一  国立研究開発法人情報通信研究機構, 脳情報通信融合研究センター脳情報通信融合研究室, 研究マネージャー (10283293)
浅田 稔  大阪大学, 先導的学際研究機構, 特任教授(常勤) (60151031)
相澤 秀紀  広島大学, 医系科学研究科(医), 教授 (80391837)
Project Period (FY) 2019-06-28 – 2024-03-31
Keywords機能回復 / 脱抑制 / fMRI / モノアミン / 高齢者 / 霊長類 / 運動野 / 半球間抑制
Outline of Annual Research Achievements

伊佐らは、2頭のサルの中部頚髄亜半切後の回復過程で.ECoGの電極を通じて一次感覚野,一次運動野,運動前野に電気刺激を行い,損傷側の前肢の筋収縮を記録したところ、1か月後のスリットを利用した把持ができる始める時には,多くの部位で筋収縮が誘発された.また.損傷反対側の一次運動野の刺激でも同様に,多くの部位で筋収縮が誘発された。さらにこのような過程で、両半球間の相互作用は損傷前は抑制的であったのに対し、回復過程においては促通性に変化することを見出した。以上の結果から,損傷後の回復過程において,損傷反対側の運動前野と一次運動野を中心に,脳内の抑制が外れる脱抑制が生じることが示唆された.
研究分担者内藤は、研究分担者浅田と共同で、右手の運動課題中に機能的MRIで計測できるNegative BOLDを指標にした、ヒトの脳領域間抑制機構の発達と加齢による劣化を可視化し、若年成人においては、右手運動中に、同側(右)運動野の手領域でみられる半球間抑制、足や顔などの体部位間抑制、視覚野や聴覚野などのクロスモダル抑制、さらにはデフォルトモードネットワークの抑制などが同定できた。
研究分担者相澤は、超適応誘導時のモノアミン神経系の関与を調べるため、急性ストレス下のマウス側坐核における細胞外ドーパミン濃度のリアルタイム測定を行った。尾懸垂下では絶望状態と闘争行動の二種類の行動パターンが交互に現れたが、闘争行動への移行に先んじて側坐核における細胞外ドーパミン濃度が一時的に減少することを明らかにした。これらの事実は、ドーパミン神経伝達と闘争行動誘発という適応行動の因果関係を示すものである。また、ヒト・サルにおける脱抑制の機構を詳細に調べるため、マウス大脳皮質の電気生理学的を応用し、半球間抑制の実験系を立ち上げた。さらに、マウス敗血症モデルにおける病態や脳機能の経時的変化について調べ、論文発表した。

Current Status of Research Progress
Current Status of Research Progress

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

Reason

研究代表者伊佐は、広汎脱抑制機構をサル2頭で再現良く確認できた。また大規模な回路再編を示す解剖学的所見も得ることができた。
研究分担者内藤は、高齢者で想定された結果を得ることができている。
研究分担者相澤は、今年度明らかにしたドーパミンの役割を基盤として半球間抑制やストレス下におけるモノアミンの役割をげっ歯類を用いた薬理学および遺伝学的手法で調べる実験基盤を確立できた。

Strategy for Future Research Activity

研究代表者伊佐は、2020年度までに明らかにした広汎脱抑制機構について論文化するとともに相澤と連携してその生理学的基盤の解明を目指す。
研究分担者内藤は、2021年度は、追加実験を行いながら、高齢者の知見をまとめると同時に、浅田グループと共同して、E/Iバランスの発達および劣化に関する数理モデル化に挑む。
研究分担者相澤は、今年度明らかにしたドーパミンの役割を基盤として半球間抑制やストレス下におけるモノアミンの役割をげっ歯類を用いた薬理学および遺伝学的手法で調べる。

  • Research Products

    (36 results)

All 2021 2020 Other

All Journal Article (18 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 18 results,  Open Access: 5 results) Presentation (14 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results) Remarks (4 results)

  • [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: 31 Pages: 2913~2931

    • DOI

      10.1093/cercor/bhaa399

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The posterior parietal cortex contributes to visuomotor processing for saccades in blindsight macaques2021

    • Author(s)
      Kato Rikako、Hayashi Takuya、Onoe Kayo、Yoshida Masatoshi、Tsukada Hideo、Onoe Hirotaka、Isa Tadashi、Ikeda Takuro
    • Journal Title

      Communications Biology

      Volume: 4 Pages: 278

    • DOI

      10.1038/s42003-021-01804-z

    • Peer Reviewed / Open Access
  • [Journal Article] Contribution of the Pulvinar and Lateral Geniculate Nucleus to the Control of Visually Guided Saccades in Blindsight Monkeys2021

    • Author(s)
      Takakuwa Norihiro、Isa Kaoru、Onoe Hirotaka、Takahashi Jun、Isa Tadashi
    • Journal Title

      The Journal of Neuroscience

      Volume: 41 Pages: 1755~1768

    • DOI

      10.1523/JNEUROSCI.2293-20.2020

    • Peer Reviewed / Open Access
  • [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: in press

    • DOI

      10.1038/s41434-020-00212-y

    • Peer Reviewed
  • [Journal Article] Repeatability of proton magnetic resonance spectroscopy of the brain at 7 T: effect of scan time on semi-localized by adiabatic selective refocusing and short-echo time stimulated echo acquisition mode scans and their comparison2021

    • Author(s)
      Okada Tomohisa、Kuribayashi Hideto、Kaiser Lana G.、Urushibata Yuta、Salibi Nouha、Seethamraju Ravi Teja、Ahn Sinyeob、Thuy Dinh Ha Duy、Fujimoto Koji、Isa Tadashi
    • Journal Title

      Quantitative Imaging in Medicine and Surgery

      Volume: 11 Pages: 9~20

    • DOI

      10.21037/qims-20-517

    • Peer Reviewed / Open Access
  • [Journal Article] Properties of visually guided saccadic behavior and bottom-up attention in marmoset, macaque, and human2021

    • Author(s)
      Chen Chih-Yang、Matrov Denis、Veale Richard、Onoe Hirotaka、Yoshida Masatoshi、Miura Kenichiro、Isa Tadashi
    • Journal Title

      Journal of Neurophysiology

      Volume: 125 Pages: 437~457

    • DOI

      10.1152/jn.00312.2020

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Optimal Model Mapping for Intravoxel Incoherent Motion MRI2021

    • Author(s)
      Liao Yen-Peng、Urayama Shin-ichi、Isa Tadashi、Fukuyama Hidenao
    • Journal Title

      Frontiers in Human Neuroscience

      Volume: 15 Pages: 617152

    • DOI

      10.3389/fnhum.2021.617152

    • Peer Reviewed
  • [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

    • Peer Reviewed
  • [Journal Article] Anatomical and electrophysiological analysis of cholinergic inputs from the parabigeminal nucleus to the superficial superior colliculus2020

    • Author(s)
      Tokuoka Kota、Kasai Masatoshi、Kobayashi Kenta、Isa Tadashi
    • Journal Title

      Journal of Neurophysiology

      Volume: 124 Pages: 1968~1985

    • DOI

      10.1152/jn.00148.2020

    • Peer Reviewed
  • [Journal Article] Dissecting the Tectal Output Channels for Orienting and Defense Responses2020

    • Author(s)
      Isa Kaoru、Sooksawate Thongchai、Kobayashi Kenta、Kobayashi Kazuto、Redgrave Peter、Isa Tadashi
    • Journal Title

      eneuro

      Volume: 7 Pages: 0271

    • DOI

      10.1523/ENEURO.0271-20.2020

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dopaminergic Signaling in the Nucleus Accumbens Modulates Stress-Coping Strategies during Inescapable Stress2020

    • Author(s)
      Cui Wanpeng、Aida Tomomi、Ito Hikaru、Kobayashi Kenta、Wada Yusaku、Kato Shigeki、Nakano Takashi、Zhu Meina、Isa Kaoru、Kobayashi Kazuto、Isa Tadashi、Tanaka Kohichi、Aizawa Hidenori
    • Journal Title

      The Journal of Neuroscience

      Volume: 40 Pages: 7241~7254

    • DOI

      10.1523/JNEUROSCI.0444-20.2020

    • Peer Reviewed
  • [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.e6

    • DOI

      10.1016/j.neuron.2020.07.013

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Oligodendrocyte dysfunction due to Chd8 mutation gives rise to behavioral deficits in mice2020

    • Author(s)
      Kawamura Atsuki、Katayama Yuta、Nishiyama Masaaki、Shoji Hirotaka、Tokuoka Kota、Ueta Yoshifumi、Miyata Mariko、Isa Tadashi、Miyakawa Tsuyoshi、Hayashi-Takagi Akiko、Nakayama Keiichi I
    • Journal Title

      Human Molecular Genetics

      Volume: 29 Pages: 1274~1291

    • DOI

      10.1093/hmg/ddaa036

    • Peer Reviewed
  • [Journal Article] Importance of the Primary Motor Cortex in Development of Human Hand/Finger Dexterity2020

    • Author(s)
      Naito Eiichi、Morita Tomoyo、Asada Minoru
    • Journal Title

      Cerebral Cortex Communications

      Volume: online ahead of print Pages: in press

    • DOI

      10.1093/texcom/tgaa085

    • Peer Reviewed
  • [Journal Article] Pharmacological and Genetic Inhibition of Translocator Protein 18 kDa Ameliorated Neuroinflammation in Murine Endotoxemia Model2020

    • Author(s)
      Giga Hiroshi、Ji Bin、Kikutani Kazuya、Fukuda Shuji、Kitajima Takashi、Katsumata Seishi、Matsumata Miho、Suhara Tetsuya、Yamawaki Shigeto、Shime Nobuaki、Hosokawa Koji、Aizawa Hidenori
    • Journal Title

      Shock

      Volume: Publish Ahead of Print Pages: in press

    • DOI

      10.1097/SHK.0000000000001703

    • Peer Reviewed
  • [Journal Article] Microglial translocator protein and stressor-related disorder2020

    • Author(s)
      Kikutani Kazuya、Giga Hiroshi、Hosokawa Koji、Shime Nobuaki、Aizawa Hidenori
    • Journal Title

      Neurochemistry International

      Volume: 140 Pages: 104855~104855

    • DOI

      10.1016/j.neuint.2020.104855

    • Peer Reviewed
  • [Journal Article] Activation of proprotein convertase in the mouse habenula causes depressive-like behaviors through remodeling of extracellular matrix2020

    • Author(s)
      Ito Hikaru、Nozaki Kanako、Sakimura Kenji、Abe Manabu、Yamawaki Shigeto、Aizawa Hidenori
    • Journal Title

      Neuropsychopharmacology

      Volume: 46 Pages: 442~454

    • DOI

      10.1038/s41386-020-00843-0

    • Peer Reviewed
  • [Journal Article] Glial glutamate transporter GLT ‐1 determines susceptibility to spreading depression in the mouse cerebral cortex2020

    • Author(s)
      Aizawa Hidenori、Sun Weinan、Sugiyama Kaori、Itou Yukiko、Aida Tomomi、Cui Wanpeng、Toyoda Saori、Terai Haruhi、Yanagisawa Michiko、Tanaka Kohichi
    • Journal Title

      Glia

      Volume: 68 Pages: 2631~2642

    • DOI

      10.1002/glia.23874

    • Peer Reviewed
  • [Presentation] Neural circuit mechanism of functional recovery after brain and spinal cord injury2021

    • Author(s)
      Tadashi Isa
    • Organizer
      第98回日本生理学大会 萩原生長記念レクチャー
  • [Presentation] Massive re-routing of corticospinal projection after functional recovery from spinal cord injury in the macaque monkey2021

    • Author(s)
      Satoko Ueno, Reona Yamaguchi, Kaoru Isa, Toshinari Kawasaki, Masahiro Mitsuhashi, Tadashi Isa
    • Organizer
      第98回日本生理学大会
  • [Presentation] アディクションの脳科学2021

    • Author(s)
      伊佐 正
    • Organizer
      日本学術会議 公開シンポジウム 「現代社会とアディクション」
  • [Presentation] Effexts of isoflurane anesthesia ond direction- and orientation- selective functional structures in mice superior colliculus2021

    • Author(s)
      Masatoshi KASAI, Tadashi ISA
    • Organizer
      第98回日本生理学大会
  • [Presentation] Systems neuroscience of functional recovery after brain and spinal cord Injur2020

    • Author(s)
      Tadashi Isa
    • Organizer
      1st Taiwan Society for Neuroscience Meeting (Plenary Lecture)
    • Int'l Joint Research / Invited
  • [Presentation] Massive re-routing of the corticospinal tract fibers accompanying recovery from spinal cord injury in macaque monkey2020

    • Author(s)
      Satoko Ueno, Reona Yamaguchi, Kaoru Isa, Toshinari Kawasaki, Masahiro Mitsuhashi, Tadashi Isa
    • Organizer
      第43回日本神経科学大会
  • [Presentation] Contribution of interhemispheric pathways between the motor-related cortical areas during recovery after the corticospinal tract lesion in macaque monkeys2020

    • Author(s)
      Masahiro Mitsuhashi, Reona Yamaguchi, Toshinari Kawasaki, Satoko Ueno, Tadashi Isa
    • Organizer
      第43回日本神経科学大会
  • [Presentation] Global disinhibition across cortical networks for recovery of hand movements after spinal cord injury2020

    • Author(s)
      Reona Yamaguchi, Toshinari Kawasaki, Zenas C Chao, Masahiro Mitsuhashi, Satoko Ueno, Tadashi Isa
    • Organizer
      第43回日本神経科学大会
  • [Presentation] Resting-state functional connectivity with electrocorticography as a biomarker of motor recovery after spinal cord injury in macaque monkeys2020

    • Author(s)
      Toshinari Kawasaki, Reona Yamaguchi, Zenas C Chao, Masahiro Mitsuhashi, Satoko Ueno, Yukihiro Yamao, Takayuki Kikuchi, Kazumichi Yoshida, Susumu Miyamoto, Tadashi Isa
    • Organizer
      第43回日本神経科学大会
  • [Presentation] Distribution of axon collaterals of ventral tegmental area-cortical motor area projection neurons in rats: a study with double infection of retrograde and anterograde viral vectors2020

    • Author(s)
      Yoshinori Koshimizu, Kaoru Isa, Kenta Kobayashi, Tadashi Isa
    • Organizer
      第43回日本神経科学大会
  • [Presentation] Cortical and subcortical mechanism of reward-based decision making2020

    • Author(s)
      Tadashi Isa
    • Organizer
      第43回日本神経科学大会(シンポジウム講演)
  • [Presentation] Mapping saccadic representation in the frontal cortex2020

    • Author(s)
      Chih-Yang Chen, Denis Matrov, ,Kuan-Ting Ho, Wajd Amly, Hirotaka Onoe, Tadashi Isa
    • Organizer
      第43回日本神経科学大会
  • [Presentation] Mapping saccadic representation in the frontal cortex2020

    • Author(s)
      Chih-Yang Chen, Denis Matrov, ,Kuan-Ting Ho, Wajd Amly, Hirotaka Onoe, Tadashi Isa
    • Organizer
      1st Taiwan Society for Neuroscience Meeting (Symposium)
    • Int'l Joint Research / Invited
  • [Presentation] Role of the amygdala for the defense-like responses induced by the stimulation of the deeper layer of superior colliculus in mice2020

    • Author(s)
      Kaoru Isa, Sooksawate Thongchai, Kota Tokuoka, Sakura Ikeda, Sara Karimi, Kenta Kobayashi, Tadashi Isa
    • Organizer
      第43回日本神経科学大会
    • 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] 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] 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/

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Published: 2021-12-27  

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