Physiology and pathophysiology of basal ganglia-thalamo-cortical projections

2018 Fiscal Year Annual Research Report

• Project/Area Number: 26250009
• Research Institution: National Institute for Physiological Sciences
• Principal Investigator: 南部 篤 生理学研究所, システム脳科学研究領域, 教授 (80180553)
• Project Period (FY): 2014-04-01 – 2019-03-31
• Keywords: 大脳基底核 / 視床 / 大脳皮質 / 淡蒼球 / 大脳基底核疾患

Outline of Annual Research Achievements

大脳基底核の出力核である淡蒼球内節から視床ー大脳皮質への情報伝達様式を調べるため、以下の実験を行った。光に応じて左あるいは右に上肢を用いて到達運動をするようにニホンザルを訓練しておく。あらかじめ大脳皮質一次運動野、補足運動野の上肢領域に刺激電極を設置しておく。また、淡蒼球内節に、黄色光によって神経活動を抑制する光感受性物質であるハロロドプシンを搭載したAAVウイルスベクターを注入しておく。淡蒼球内節から視床への投射終末にハロロドプシンが発現するのを待って、記録電極に光ファイバーを貼り付けたオプトロードを、視床内に刺入した。大脳皮質を電気刺激し逆行性応答により、また淡蒼球内節を電気刺激し、抑制性応答を記録することにより、淡蒼球内節から入力を受け、大脳皮質運動野に投射する視床ニューロンであることを同定した。次に、淡蒼球内節を電気刺激し、同時に光ファイバーから黄色レーザー光を照射すると、抑制性応答が減弱することが分かった。すなわち、光照射により、淡蒼球内節ー視床伝達が抑制されていることが示された。さらに、サルに運動課題を遂行させ、その際の視床ニューロンの活動を記録したところ、運動に際して興奮するものが多く記録できた。次に、運動中に黄色レーザー光を照射したところ、運動に伴う興奮性活動が減弱することがわかった。これまで大脳基底核からの抑制から脱することにより、視床が活動すると考えられてきた（脱抑制説）が、本結果は、大脳基底核からの抑制後のリバウンド興奮によって、視床に信号を伝達していることを強く示唆するものである。

Research Progress Status

平成30年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成30年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] HM CINAC(スペイン)
  • Country Name: SPAIN
  • Counterpart Institution: HM CINAC
• [Int'l Joint Research] Lund大学/スウェーデン王立工科大学(スウェーデン)
  • Country Name: SWEDEN
  • Counterpart Institution: Lund大学/スウェーデン王立工科大学
• [Journal Article] Recruitment of calbindin into nigral dopamine neurons protects against drug-induced parkinsonism (2019)
  • Author(s): Inoue K, Miyachi S, Nishi K, Okado H, Nagai Y, Minamimoto T, Nambu A, Takada M
  • Journal Title: Mov Disord Volume: 34(2) Pages: 200-209
  • DOI: 10.1002/mds.107
  • Peer Reviewed
• [Journal Article] Sensory nerve supports epithelial stem cell function in healing of corneal epithelium in mice: the role of trigeminal nerve transient receptor potential vanilloid 4 (2019)
  • Author(s): Okada Y, Sumioka T, Ichikawa K, Sano H, Nambu A, Kobayashi K, Uchida K, Suzuki Y, Tominaga M, Reinach PS, Hirai SI, Jester JV, Miyajima M, Shirai K, Iwanishi H, Kao WW, Liu CY, and Saika S
  • Journal Title: Lab Invest Volume: 99(2) Pages: 210-230
  • DOI: 10.1038/s41374-018-0118-4
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The effect of zonisamide on L-DOPA-induced dyskinesia in Parkinson’s disease model mice (2019)
  • Author(s): Sano H, Nambu A
  • Journal Title: Neurochem Int Volume: 124 Pages: 171-180
  • DOI: 10.1016/j.neuint.2019.01.011
  • Peer Reviewed / Open Access
• [Journal Article] Two-photon imaging of neuronal activity in motor cortex of marmosets during upper-limb movement tasks (2018)
  • Author(s): Ebina T, Masamizu Y, Tanaka YR, Watakabe A, Hirakawa R, Hirayama Y, Hira R, Terada S, Koketsu D, Hikosaka K, Mizukami H, Nambu A, Sasaki E, Yamamori Y, Matsuzaki M
  • Journal Title: Nat Commun Volume: 9(1) Pages: 1879
  • DOI: 10.1038/s41467-018-04286-6
  • Peer Reviewed / Open Access
• [Journal Article] Monitoring and updating of action selection for goal-directed behavior through the striatal direct and indirect pathways (2018)
  • Author(s): Nonomura S, Nishizawa K, Sakai Y, Kawaguchi Y, Kato S, Uchigashima M, Watanabe M, Yamanaka K, Enomoto K, Chiken S, Sano H, Soma S, Yoshida J, Samejima K, Ogawa M, Kobayashi K, Nambu A, Isomura Y, Kimura M
  • Journal Title: Neuron Volume: 99(6) Pages: 1302-1314.e5
  • DOI: 10.1016/j.neuron.2018.08.002
  • Peer Reviewed
• [Journal Article] Length of myelin internodes of individual oligodendrocytes are controlled by microenvironment influenced by normal and input-deprived axonal activities in sensory deprived mouse models (2018)
  • Author(s): Osanai Y, Shimizu T, Mori T, Hatanaka N, Kimori Y, Kobayashi K, Yoshimura Y, Nambu A, Ikenaka K
  • Journal Title: Glia Volume: 66(11) Pages: 2514-2525
  • DOI: 10.1002/glia.23502
  • Peer Reviewed
• [Journal Article] New neurons use Slit-Robo signaling to migrate through the glial meshwork and approach the lesion for functional regeneration (2018)
  • Author(s): Kaneko N, Herranz-Perez V, Otsuka T, Sano H, Ohno N, Omata T, Nguyen HB, Thai TQ, Nambu A, Kawaguchi Y, Garcia-Verdugo JM, Sawamoto K
  • Journal Title: Sci Adv Volume: 4(12) Pages: eaav0618
  • DOI: 10.1126/sciadv.aav0618.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Neurophysiological studies of motor-related areas in awake common monkeys (2019)
  • Author(s): Koketsu D, Nambu A
  • Organizer: International Symposium of Brain/MINDS ISMB2019 (東京)
• [Presentation] 覚醒下マーモセットからの神経活動記録法 (2019)
  • Author(s): 南部 篤
  • Organizer: 第８回日本マーモセット研究会（東京
  • Invited
• [Presentation] Cortical control of subthalamic nucleus activity in awake monkeys (2019)
  • Author(s): Polyakova Z, Hatanaka N, Chiken S, Nambu A
  • Organizer: 11th Nagoya Global Retreat (Nagoya)
• [Presentation] マーモセット前頭連合野機能マッピングのための記憶課題の確立 (2019)
  • Author(s): 纐纈大輔、南部篤
  • Organizer: 第８回日本マーモセット研究会（東京）
• [Presentation] Parkinson’s disease as a network disorder (2019)
  • Author(s): Nambu A
  • Organizer: System Neuroscience Spring School 2019 (京都)
  • Invited
• [Presentation] 視床下核による運動制御：マカクザル視床下核の化学遺伝学的抑制による運動異常 (2019)
  • Author(s): 長谷川拓
  • Organizer: 平成30年度 京都大学 霊長類研究所 共同利用研究会（犬山）
  • Invited
• [Presentation] Physiological and anatomical organization of cortico-striatal inputs in the basal ganglia (2019)
  • Author(s): Sano H, Kobayashi K, Kato S, Chiken S, Kobayashi K, Nambu A
  • Organizer: 9th FAOPS Congress (神戸)
• [Presentation] How does the cerebellum control thalamocortical activity? (2019)
  • Author(s): Chiken S, Sano H, Kobayashi K, Nambu A
  • Organizer: 9th FAOPS Congress (神戸)
• [Presentation] Neuronal responses and movements induced by concurrent activation of striatonigral and striatopallidal neurons (2018)
  • Author(s): Sano H, Tanaka KF, Nambu A
  • Organizer: FENS2018 (Berlin, Germany)
  • Int'l Joint Research
• [Presentation] Modulation of basal ganglia pathways after chronic L-dopa treatment in Parkinson`s disease (2018)
  • Author(s): Indriani Dwi Wahyu, Sano H, Chiken S, Nambu A
  • Organizer: FENS2018 (Berlin, Germany)
  • Int'l Joint Research
• [Presentation] Cerebellar control of thalamocortical activity (2018)
  • Author(s): Chiken S, Sano H, Kobayashi K, Nambu A
  • Organizer: FENS2018 (Berlin, Germany)
  • Int'l Joint Research
• [Presentation] Cortico-basal ganglia loop and movement disorders (2018)
  • Author(s): Nambu A
  • Organizer: 第４１回日本神経科学大会（神戸）
  • Invited
• [Presentation] Chronic L-dopa treatment alters basal ganglia signaling in Parkinson’s disease model mice (2018)
  • Author(s): Indriani Dwi Wahyu, Sano H, Chiken S, Nambu A
  • Organizer: 第４１回日本神経科学大会（神戸）
• [Presentation] Cerebellar outputs modulate neuronal activity in the primary motor cortex during movement execution in macaque monkeys (2018)
  • Author(s): Sano N, Nakayama Y, Hoshi E, Chiken S, Nambu A, Nishimura Y
  • Organizer: 第４１回日本神経科学大会（神戸）
• [Presentation] Elucidation of motor control mechanism using genetically mice harboring tetracycline regulated expression on D1/D2 dopamine receptors (2018)
  • Author(s): Sasaoka T, Sato A, Chiken S, Okubo T, Abe M, Kawamura M, Saito N, Oda K, Sakuma T, Uchiyama S, Abe M, Tanaka M, Yamamoto Y, Jimbo Y, Sato T, Fujisawa N, Sakimura K, Nambu A
  • Organizer: 第４１回日本神経科学大会（神戸）
• [Presentation] Cortical control of monkey subthalamic nucleus by the hyperdirect and indirect pathways (2018)
  • Author(s): Polyakova Z, Hatanaka N, Chiken S, Nambu A
  • Organizer: 第４１回日本神経科学大会（神戸）
• [Presentation] Identification of indirect pathway neurons and dopaminergic innervation in the rat dorsal striatum (2018)
  • Author(s): Nonomura S, Kato S, Iguchi Y, Nishizawa K, Sakai Y, Kawaguchi Y, Nambu A, Watanabe M, Kobayashi K, Isomura Y, Kimura M
  • Organizer: 第４１回日本神経科学大会（神戸）
• [Presentation] Silencing of FUS in common marmoset caudate induces shortening of fiber tracts accompanied with glial inflammation (2018)
  • Author(s): Endo K, Ishigaki S, Watanabe H, Masamizu Y, Hatanaka N, Hata J, Watakabe A, Matsuzaki M, Nambu A, Okano H, Yamamori T, Katsuno M, Sobue G
  • Organizer: 第４１回日本神経科学大会（神戸）
• [Presentation] Basal ganglia and cerebellar control of thalamocortical activity (2018)
  • Author(s): Chiken S, Sano H, Kobayashi K, Nambu A
  • Organizer: 第２回NIPS-ARIHHP Joint orkshop Human High Performance-oriented Sports Neuroscience by Integrating Basic Neuroscience （岡崎）
• [Presentation] 大脳基底核による運動制御 (2018)
  • Author(s): 南部 篤
  • Organizer: 第２回NIPS-ARIHHP Joint orkshop Human High Performance-oriented Sports Neuroscience by Integrating Basic Neuroscience （岡崎）
  • Invited
• [Presentation] 大脳基底核による運動制御：マカクザル視床下核の化学遺伝学的な活動制御 (2018)
  • Author(s): 長谷川拓、知見聡美、小林憲太、南部篤
  • Organizer: 第33回日本大脳基底核研究会（東京）
• [Presentation] モデルマウスの神経活動からジストニアの病態生理を探る (2018)
  • Author(s): 知見聡美、南部篤
  • Organizer: 第33回日本大脳基底核研究会（東京）
• [Presentation] The role of hyperdirect and indirect pathways in the formation of cortically induced bi-phasic response in monkey subthalamic nucleus (2018)
  • Author(s): Polyakova Z, Hatanaka N, Chiken S, Nambu A
  • Organizer: 8th National Institute of Physiology - Nagoya University Graduate School of Medicine Joint symposium (Nagoya)
• [Presentation] How do the basal ganglia and cerebellum control thalamocortical activity? (2018)
  • Author(s): Chiken S
  • Organizer: 8th Joint CIN-NIPS Symposium (Tuebingen)
  • Int'l Joint Research / Invited
• [Presentation] Inhibitory center-excitatory surround" organization of the basal ganglia revealed by optogenetic stimulation (2018)
  • Author(s): Nambu A
  • Organizer: 8th Joint CIN-NIPS Symposium (Tuebingen)
• [Presentation] The impact of glutamatergic and GABAergic inputs to the subthalamic nucleus activity in monkey (2018)
  • Author(s): Polyakova Z, Hatanaka N, Chiken S, Nambu A
  • Organizer: McGill University and Natl Inst Physiol Sci Joint symposium (Okazaki)
• [Presentation] Parkinson’s disease as a network disorder (2018)
  • Author(s): Nambu A
  • Organizer: Symposio Cajal 2018 (Madrid, Spain)
  • Int'l Joint Research / Invited
• [Presentation] Parkinson’s disease as a network disorder (2018)
  • Author(s): Nambu A
  • Organizer: XXXVI Annual Meeting of Indian Academy of Neuroscience (Varanasi, India)
  • Int'l Joint Research / Invited
• [Presentation] Silencing of FUS in the caudate nucleus of non-human primates induces disruption of its fiber bundles (2018)
  • Author(s): Endo K, Ishigaki S, Hatanaka N, Hata J, Watanabe H, Katsuno M, Nambu A, Okano H, Yamamori T, Sobue G
  • Organizer: Neuroscience 2018 (San Diego)
• [Presentation] Cerebellar outputs contribute to the activity of the primary motor cortex during arm-reaching movement in macaque monkeys (2018)
  • Author(s): Sano N, Nakayama Y, Hoshi E, Chiken S, Nambu A, Nishimura Y
  • Organizer: Neuroscience 2018 (San Diego)
• [Presentation] The chemogenetic suppression of the primate subthalamic nucleus impairs voluntary movements by disturbing the firing pattern in the internal segment of the globus pallidus (2018)
  • Author(s): Hasegawa T, Chiken S, Kobayashi K, Nambu A
  • Organizer: Neuroscience 2018 (San Diego)
• [Presentation] The impact of glutamatergic and GABAergic inputs to the subthalamic nucleus activity in monkey (2018)
  • Author(s): Polyakova Z, Hatanaka N, Chiken S, Kita H, Nambu A
  • Organizer: Neuroscience 2018 (San Diego)
• [Presentation] Glutamatergic and GABAergic controls of the subthalamic nucleus activity in monkeys (2018)
  • Author(s): Polyakova Z, Hatanaka N, Chiken S, Nambu A
  • Organizer: 30th Annual Basal Ganglia Function Research Association meeting (Aizu-Wakamatsu, Fukushima)
• [Presentation] The role of hyperdirect and indirect pathways in the formation of cortically induced bi-phasic response in monkey subthalamic nucleus (2018)
  • Author(s): Polyakova Z, Hatanaka N, Chiken S, Nambu A
  • Organizer: Life Science Retreat 2018 (Yamanashi, Lake-Kawaguchiko)
• [Presentation] Correlated activity in the globus pallidus of normal and MPTP-treated Parkinson's disease monkeys (2018)
  • Author(s): Woranan Wongmassang
  • Organizer: 生理学研究所研究会「行動を制御する神経ネットワーク機能の解明に向けて」（岡崎）
  • Invited
• [Presentation] Na pump dysfunction may cause dystonia by enhancing cortico-striato-pallidal neurotransmission (2018)
  • Author(s): Nambu A, Chiken S
  • Organizer: 第４１回日本分子生物学会年会（横浜）
• [Presentation] モデル動物の神経活動からジストニアの病態を考える (2018)
  • Author(s): 知見聡美、南部篤
  • Organizer: 第17回ジストニア研究会（東京）
  • Invited
• [Remarks] 生理学研究所 生体システム研究部門 web site
  • URL: http://www.nips.ac.jp/sysnp