Deep brain oscillation and motor control in primate and rodent models

2018 Fiscal Year Annual Research Report

• Project Area: Non-linear Neuro-oscillology: Towards Integrative Understanding of Human Nature
• Project/Area Number: 15H05873
• 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): 2015-06-29 – 2020-03-31
• Keywords: 脳、神経 / 脳神経疾患 / ソフトコンピューティング / 神経科学 / 生理学

Outline of Annual Research Achievements

霊長類、げっ歯類モデルでの脳深部振動と運動制御に関して、以下の研究を行った。
パーキンソン病の病態生理に関して、これまで大脳基底核や視床の神経活動が調べられており、平均発射頻度の変化や発射パターンの変化などが報告されてきた。しかし、大脳基底核をめぐる情報伝達の変化がより重要ではないかと考え、本実験を行った。ドーパミン神経毒であるMPTPをニホンザルに投与し、パーキンソン病モデルサルを作製した。また、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埋めておいた。覚醒下で淡蒼球外節および内節に記録電極を挿入、神経活動を記録し、大脳皮質一次運動野、補足運動野を電気刺激することにより反応を記録した。（１）正常なサルにおいては大脳皮質を電気刺激すると、淡蒼球外節／内節は早い興奮―抑制―遅い興奮からなる３相性の応答が記録できる。パーキンソン病においては、淡蒼球内節では抑制が減少し、淡蒼球外節では遅い興奮が増大していた。（２）L―ドパを全身投与すると、サルのパーキンソン病症状は改善するが、それに伴って、淡蒼球内節では抑制が回復し、淡蒼球外節の遅い興奮が減少した。（３）視床下核にムシモルを注入して神経活動をブロックしても、パーキンソン病症状が改善するが、それと同時に大脳皮質由来の淡蒼球内節での抑制が回復した。大脳皮質由来の淡蒼球内節での抑制は大脳皮質―線条体―淡蒼球内節路（直接路）を介しているが、この抑制が投射先である視床の脱抑制を引き起こし、運動を惹起していると考えられる。パーキンソン病においては、この抑制が減少しているため、運動を引き起こせなくなった、即ち無動に至ったと考えられる。また、L-ドパ療法や視床下核のブロックにおいては、淡蒼球内節の抑制が回復することによって症状が改善すると考えられる。

Current Status of Research Progress

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

Reason

霊長類モデル、げっ歯類モデルを使った研究が順調に進んでいる。とくにパーキンソン病の病態メカニズムや治療法について新たな知見を得ることができた。

Strategy for Future Research Activity

これまでの成果をとりまとめ、論文化を目指す。

Research Products

• [Int'l Joint Research] CINAC(スペイン)
  • Country Name: SPAIN
  • Counterpart Institution: CINAC
• [Int'l Joint Research] KTH Royal Institute of Technology/Lund University(スウェーデン)
  • Country Name: SWEDEN
  • Counterpart Institution: KTH Royal Institute of Technology/Lund University
• [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] 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 Pages: 210-230
  • DOI: 10.1038/s41374-018-0118-4
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Development of stereotaxic recording system for awake marmosets (Callithrix jacchus). (2018)
  • Author(s): Wakabayashi M, Koketsu D, Kondo H, Sato S, Ohara K, Polyakova Z, Chiken S, Hatanaka N, Nambu A
  • Journal Title: Neurosci Res Volume: 135 Pages: 37-45
  • DOI: 10.1016/j.neures.2018.01.001
  • 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 Pages: 1879
  • DOI: 10.1038/s41467-018-04286-6
  • Peer Reviewed / Open Access
• [Journal Article] Recruitment of calbindin into nigral dopamine neurons protects against drug-induced parkinsonism. (2018)
  • Author(s): Inoue K, Miyachi S, Nishi K, Okado H, Nagai Y, Minamimoto T, Nambu A, Takada M
  • Journal Title: Mov Disord Volume: 34 Pages: 200-209
  • DOI: 10.1002/mds.107
  • Peer Reviewed
• [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 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 / 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] 生体システム研究部門
  • URL: https://www.nips.ac.jp/sysnp/
• [Patent(Industrial Property Rights)] 特許 (2018)
  • Inventor(s): 南部篤、知見聡美、西村幸男、高良沙幸
  • Industrial Property Rights Holder: 自然科学研究機構
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 特許第6300208