Neural mechanism of tic disorders revealed by optical imaging in the brain

• Project/Area Number: 18K06852
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Kobe University
• Principal Investigator: Tachibana Yoshihisa 神戸大学, 医学研究科, 准教授 (50373197)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 大脳基底核 / 線条体 / GABA / 不随意運動 / 情動 / 2光子顕微鏡イメージング / 光遺伝学

Outline of Final Research Achievements

The pathophysiology of motor and vocal tics remains unknown. Recently, the disinhibition of the striatum is suggested to cause the tic symptoms. To test this issue, we unilaterally injected GABA antagonist bicuculline into the mouse striatum. We found that the local bicuculline into the striatum induced contralateral muscle twitches depending on injection sites. Then, we investigated the activated brain regions by striatal disinhibition using c-Fos immunohistochemistry. We found that limbic structures such as the amygdala, cingulate cortex, insular cortex as well as the primary motor cortex were activated although the structure does not receive direct inputs from the striatum. These data suggest that the tic is generated by abnormal neuronal processing in the motor-limbic network in the brain.

Academic Significance and Societal Importance of the Research Achievements

トゥレット症候群に代表されるように、運動チックや音声チックを患い、薬物療法、認知行動療法が奏功しない患者が数多くいる。その理由として、チック症の神経生理学的な病態メカニズムが明らかになっていないことが挙げられる。本研究において、大脳基底核の機能異常を起因とし、情動と運動をつなぐ神経ネットワークの情報処理の異常からチック症状が惹起されうることが明らかとなった。本研究成果は、生活上の困難さやハンディキャップを持ったまま社会生活を送らざるをえないチック症患者にとって、症状を緩和させる新たな治療法の開発に大いに役立つと期待される。

Research Products

• [Journal Article] Motor learning requires myelination to reduce asynchrony and spontaneity in neural activity (2020)
  • Author(s): Kato Daisuke、Wake Hiroaki、Lee Philip R.、Tachibana Yoshihisa、Ono Riho、Sugio Shouta、Tsuji Yukio、Tanaka Yasuyo H.、Tanaka Yasuhiro R.、Masamizu Yoshito、Hira Riichiro、Moorhouse Andrew J.、Tamamaki Nobuaki、Ikenaka Kazuhiro、Matsukawa Noriyuki、Fields R. Douglas、Nabekura Junichi、Matsuzaki Masanori
  • Journal Title: Glia Volume: 68 Pages: 193-210
  • DOI: 10.1002/glia.23713
  • NAID: 120006775953
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Oral splint ameliorates tic symptoms in patients with tourette syndrome (2019)
  • Author(s): Murakami Jumpei、Tachibana Yoshihisa、Akiyama Shigehisa、Kato Takafumi、Taniguchi Aya、Nakajima Yoshiaki、Shimoda Mao、Wake Hiroaki、Kano Yukiko、Takada Masahiko、Nambu Atsushi、Yoshida Atsushi
  • Journal Title: Mov Disord Volume: 34 Pages: 1577-1578
  • DOI: 10.1002/mds.27819
  • NAID: 120006799316
  • Peer Reviewed / Open Access
• [Journal Article] Dual microglia effects on blood brain barrier permeability induced by systemic inflammation (2019)
  • Author(s): Haruwaka K., Ikegami A., Tachibana Y., Ohno N., Konishi H., Hashimoto A., Matsumoto M., Kato D., Ono R., Kiyama H., Moorhouse A. J., Nabekura J., Wake H.
  • Journal Title: Nature Communications Volume: 10 Pages: 5816-5816
  • DOI: 10.1038/s41467-019-13812-z
  • NAID: 120006786954
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Direct and indirect pathways for choosing objects and actions. (2019)
  • Author(s): Okihide Hikosaka, Hyong F. Kim, Hidetoshi Amita, Masaharu Yasuda, Masaki Isoda, Yoshihisa Tachibana, Atsushi Yoshida
  • Journal Title: European Journal of Neuroscience Volume: - Pages: 637-645
  • DOI: 10.1111/ejn.13876
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Cortical and Subcortical Projections from Granular Insular Cortex Receiving Orofacial Proprioception (2018)
  • Author(s): Tsutsumi Yumi、Tachibana Yoshihisa、Sato Fumihiko、Furuta Takahiro、Ohara Haruka、Tomita Akiko、Fujita Masatoshi、Moritani Masayuki、Yoshida Atsushi
  • Journal Title: Neuroscience Volume: 388 Pages: 317-329
  • DOI: 10.1016/j.neuroscience.2018.07.047
  • Peer Reviewed
• [Journal Article] Transcortical descending pathways through granular insular cortex conveying orofacial proprioception (2018)
  • Author(s): Ikenoue Etsuko、Akhter Fatema、Tsutsumi Yumi、Sato Fumihiko、Ohara Haruka、Uchino Katsuro、Furuta Takahiro、Tachibana Yoshihisa、Yoshida Atsushi
  • Journal Title: Brain Research Volume: 1687 Pages: 11-19
  • DOI: 10.1016/j.brainres.2018.02.033
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Microglia Enhance Synapse Activity to Promote Local Network Synchronization (2018)
  • Author(s): Akiyoshi R., Wake H., Kato D., Horiuchi H., Ono R., Ikegami A., Haruwaka K., Omori T., Tachibana Y., Noorhouse A. J., Nabekura J.
  • Journal Title: eNeuro Volume: 5 Pages: 0088-18
  • DOI: 10.1523/eneuro.0088-18.2018
  • NAID: 120006549205
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 淡蒼球外節は基底核回路における間接路の単なる中継核か？ (2020)
  • Author(s): 橘 吉寿
  • Organizer: 第97回日本生理学会大会
• [Presentation] 皮質線条体ニューロンと皮質視床下核ニューロンの機能的差異 (2020)
  • Author(s): 橘 吉寿
  • Organizer: 第97回日本生理学会大会
• [Presentation] Neuronal response to whisker stimulation in the visual cortex of monocular deprived mice in vivo. (2019)
  • Author(s): 橋本 明香里、宮本 愛喜子、橘 吉寿、春若航一路、和氣 弘明
  • Organizer: 第42回日本神経科学大会
• [Presentation] Change of lipid profile in myelin associated with motor learning affect on neuronal activity pattern in primary motor cortex. (2019)
  • Author(s): 西田 一貴、橘 吉寿、佐藤 駿平、山崎 文義、瀬藤 光利、和氣 弘明
  • Organizer: 第42回日本神経科学大会
• [Presentation] Synchronized activity in the primary motor cortex of parkinsonian mice revealed by two-photon Ca2+ imaging. (2019)
  • Author(s): 橘 吉寿、青山 友紀、和氣 弘明
  • Organizer: 第42回日本神経科学大会
• [Presentation] Visual cortex activity with whisker stimulation in monocular deprived mice in vivo. (2018)
  • Author(s): 橋本 明香里、宮本 愛喜子、橘 吉寿、春若航一路、和氣 弘明
  • Organizer: 第41回日本神経科学大会
• [Presentation] In vivo Ca2+ imaging of primary somatosensory cortex in a mouse model of postoperative pain. (2018)
  • Author(s): 岡田 卓也、橘 吉寿、野村 有紀、小幡 典彦、溝渕 知司、和氣 弘明
  • Organizer: 第41回日本神経科学大会
• [Presentation] 運動と意欲を繋ぐ大脳基底核 (2018)
  • Author(s): 橘 吉寿
  • Organizer: ヒューマン・ハイ・パフォーマンスの実現を目指した次世代健康スポーツ科学と神経科学の融合・統合
  • Invited
• [Presentation] 大脳基底核の機能を探る (2018)
  • Author(s): 橘 吉寿
  • Organizer: 昭和大学学士会後援セミナー
  • Invited
• [Presentation] 脳機能ネットワークの破綻として捉える大脳基底核疾患 (2018)
  • Author(s): 橘 吉寿
  • Organizer: 生体システム連関研究会
• [Presentation] 大脳基底核の解剖・機能 (2018)
  • Author(s): 橘 吉寿
  • Organizer: 産業技術総合研究所 部門セミナー
  • Invited
• [Presentation] 大脳基底核の解剖と生理 (2018)
  • Author(s): 橘 吉寿
  • Organizer: 北海道大学大学院医学研究科共通セミナー
  • Invited
• [Presentation] In vivo tracing of single neuron activity with Ca2+ imaging of primary somatosensory cortex in mouse models of postoperative pain and inflammatory pain. (2018)
  • Author(s): Okada, T., Tachibana, Y., Nomura, Y., Obata, N., Mizobuchi, S., Wake, H.
  • Organizer: SOCIETY FOR NEUROSCIENCE 48TH ANNUAL MEETING
  • Int'l Joint Research
• [Presentation] 運動学習と関連した白質における脂質の変化が一次運動野の神経活動に及ぼす影響 (2018)
  • Author(s): 西田 一貴、橘 吉寿、佐藤 駿平、山崎 文義、瀬藤 光利、和氣 弘明
  • Organizer: 第111回近畿生理学談話会
• [Presentation] 大脳皮質感覚野の生体イメージングによる疼痛発症機構解明へのアプローチ (2018)
  • Author(s): 岡田 卓也、橘 吉寿、野村 有紀、小幡 典彦、溝渕 知司、和氣 弘明
  • Organizer: 第111回近畿生理学談話会
• [Presentation] Change of lipid profile in myelin associated with motor learning affect on neuronal activity pattern in primary motor cortex. (2018)
  • Author(s): 西田 一貴、橘 吉寿、佐藤 駿平、山崎 文義、瀬藤 光利、和氣 弘明
  • Organizer: 第23回グリア研究会
• [Presentation] In vivo Ca2+ imaging of somatosensory cortex in postoperative an inflammatory pain models of mice. (2018)
  • Author(s): Okada, T., Tachibana, Y., Nomura, Y., Obata, N., Mizobuchi, S., Wake, H.
  • Organizer: 9TH FAOPS CONGRESS
  • Int'l Joint Research
• [Presentation] The response to whisker stimulation in the visual cortex of monocular deprived mice in vivo. (2018)
  • Author(s): Hashimoto, A., Miyamoto, A., Tachibana, Y., Haruwaka, K., Wake, H.
  • Organizer: 9TH FAOPS CONGRESS
  • Int'l Joint Research
• [Funded Workshop] SOCIETY FOR NEUROSCIENCE 48TH ANNUAL MEETING (2018)