Functional significance of the dual transmission by the cerebro-cerebellar pathway

• Project/Area Number: 18K06529
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46030:Function of nervous system-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Ishikawa Taro 東京慈恵会医科大学, 医学部, 准教授 (50547916)
• Co-Investigator(Kenkyū-buntansha): 志牟田 美佐 東京慈恵会医科大学, 医学部, 講師 (70609172)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 大脳小脳連関 / プルキンエ細胞 / 小脳顆粒細胞 / 橋核 / 小脳 / 光遺伝学 / オプトジェネティクス / 体性感覚 / 運動学習

Outline of Final Research Achievements

In vivo recordings from cerebellar granule cells in mice, in which the neocortex can be optogenetically suppressed, showed that tactile stimulus responses in granule cells were bimodal, with only slow responses being neocortex-dependent. In Purkinje cells, the slow simple spikes and complex spikes evoked by tactile stimulation were neocortex-dependent. These results indicated that individual granule cells combine convergent inputs from the periphery and neocortex and send their outputs to Purkinje cells, which then integrate those signals with climbing fiber signals from the neocortex.

Academic Significance and Societal Importance of the Research Achievements

本研究は実験動物（マウス）を用いて大脳から小脳への信号の連絡様式について基本的な仕組みを示したものだが、同様の回路はヒトでも機能しているものと考えられる。さらに、動物に比べて、ヒトはより大きな大脳を持つため、大脳と小脳の結びつき(大脳小脳連関)はより強力であると考えられている。小脳は体の運動の制御に重要であるが、それのみならず、近年では、原因が未だ明らかでない自閉症スペクトラム障害などの異常においても、大脳と小脳の連関の異常が影響していることが示唆されている。本研究で明らかになった回路原理は、様々な疾患とその治療の研究の基礎となるものである。

Research Products

• [Journal Article] Multiple signals evoked by unisensory stimulation converge onto cerebellar granule and Purkinje cells in mice (2020)
  • Author(s): Misa Shimuta, Izumi Sugihara, Taro Ishikawa
  • Journal Title: Communications biology Volume: 3(1) Issue: 1 Pages: 381-381
  • DOI: 10.1038/s42003-020-1110-2
  • Peer Reviewed / Open Access
• [Journal Article] De novo CACNA1G variants in developmental delay and early-onset epileptic encephalopathies (2020)
  • Author(s): Misako Kunii, Hiroshi Doi, Shunta Hashiguchi, Toyojiro Matsuishi, Yasunari Sakai, Mizue Iai, Masaki Okubo, Haruko Nakamura, Keita Takahashi, Atsuko Katsumoto, Mikiko Tada, Hideyuki Takeuchi, Taro Ishikawa, Noriko Miyake, Hirotomo Saitsu, Naomichi Matsumoto, Fumiaki Tanaka
  • Journal Title: Journal of the Neurological Sciences Volume: 416 Pages: 117047-117047
  • DOI: 10.1016/j.jns.2020.117047
  • Peer Reviewed / Open Access
• [Journal Article] Convergence of unisensory-evoked signals via multiple pathways to the cerebellum (2019)
  • Author(s): Misa Shimuta, Izumi Sugihara, Taro Ishikawa
  • Journal Title: bioRxiv Volume: －
  • DOI: 10.1101/769000
  • Open Access
• [Journal Article] Ataxic phenotype with altered CaV3.1 channel property in a mouse model for spinocerebellar ataxia 42 (2019)
  • Author(s): Hashiguchi S, Doi H, Kunii M, Nakamura Y, Shimuta M, （32名略） Ishikawa T, Tanaka F
  • Journal Title: Neurobiology of Disease Volume: 130 Pages: 104516-104516
  • DOI: 10.1016/j.nbd.2019.104516
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 小脳における感覚信号の統合 (2022)
  • Author(s): 石川太郎
  • Organizer: 日本小脳学会第12回学術集会
  • Invited
• [Presentation] Multiple cortico-cerebellar pathways in sensory signaling (2020)
  • Author(s): Taro Ishikawa
  • Organizer: 第43回日本神経科学大会
  • Invited
• [Presentation] Convergence of sensory-evoked signals via multiple pathways in the cerebellum (2019)
  • Author(s): Taro Ishikawa, Izumi Sugihara, Misa Shimuta
  • Organizer: Society for Neuroscience Annual Meeting
  • Int'l Joint Research
• [Presentation] プルキンエ細胞と顆粒細胞における大脳小脳連関信号の統合 (2019)
  • Author(s): 石川太郎
  • Organizer: 第13回Motor control研究会, シンポジウム「小脳が関与する制御機能の最前線 -基礎と臨床の融合を目指して」
  • Invited
• [Presentation] Convergence of sensory-evoked multi-pathway signals in the cerebellum (2019)
  • Author(s): 志牟田美佐, 杉原泉, 石川太郎
  • Organizer: 第42回日本神経科学大会
• [Presentation] Cerebellar integration of neocortical somatosensory signals (2019)
  • Author(s): Misa Shimuta, Izumi Sugihara, Taro Ishikawa
  • Organizer: FAOPS2019
  • Int'l Joint Research
• [Presentation] Cerebellar integration of multiple input signals (2018)
  • Author(s): Misa Shimuta，Izumi Sugihara，Taro Ishikawa
  • Organizer: The 75th Fujihara seminar
  • Int'l Joint Research
• [Presentation] Processing of sensory-evoked signals in the cerebro-cerebellar communication (2018)
  • Author(s): Taro Ishikawa
  • Organizer: 河北医科大学病理生理学高端学術論壇
  • Invited
• [Remarks] 研究室webページ
  • URL: http://www.jikei-pharm.com/member/ishikawa
• [Remarks] プレスリリース:大脳からの信号と末梢神経からの信号が小脳の神経回路において統合される
  • URL: http://www.jikei.ac.jp/news/press_release_20200716.html
• [Remarks] 小脳入力信号の機能的解析
  • URL: http://www.jikei-pharm.com/member/ishikawa