Functional roles of the electrical activity in postnatal refinement of the neuronal circuitry

• Project/Area Number: 17H03551
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Hiroshima University
• Principal Investigator: Hashimoto Kouichi 広島大学, 医系科学研究科(医), 教授 (00303272)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2020: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: シナプス刈り込み / 登上線維 / プルキンエ細胞 / 下オリーブ核 / 小脳 / 神経回路

Outline of Final Research Achievements

Neural circuits in neonatal animals involve redundant synapses that are not observed in the adult brain. During the postnatal period, less important synapses are eliminated while functionally important ones are strengthened. This process is thought to be prerequisite for construction of functional neuronal circuits. In the present study, I examined mechanisms that regulate the postnatal circuit refinement using cerebellar climbing fiber to Purkinje cells synapses as a model system.

Academic Significance and Societal Importance of the Research Achievements

生まれた後の生育期における正常な神経回路の成熟には、遺伝子による制御とともに適切な生育環境に暴露されることが必要である。正常な神経回路成熟の阻害は、発達障害等の発症の要因となるとされている。本研究は、幼若期の神経回路が正常に成熟するために働くメカニズムの一端を明らかにするとともに、将来的に発達障害発症機序の解明や治療法の開発などにも貢献することが期待される。

Research Products

• [Journal Article] Kv11 (ether-a-go-go-related gene) voltage-dependent K + channels promote resonance and oscillation of subthreshold membrane potentials (2021)
  • Author(s): Matsuoka Toshinori, Yamasaki Miwako, Abe Manabu, Matsuda Yukiko, Morino Hiroyuki, Kawakami Hideshi, Sakimura Kenji, Watanabe Masahiko, Hashimoto Kouichi
  • Journal Title: The Journal of Physiology Volume: 599(2) Issue: 2 Pages: 547-569
  • DOI: 10.1113/jp280342
  • Peer Reviewed / Open Access
• [Journal Article] 小脳への感覚信号の伝達経路 (2021)
  • Author(s): 久保怜香 橋本浩一
  • Journal Title: 生体の科学 Volume: 72 Pages: 18-22
• [Journal Article] Component of nicotine-induced intracellular calcium elevation mediated throughα3- andα5-containing nicotinic acetylcholine receptors are regulated by cyclic AMP in SH-SY 5Y cells (2020)
  • Author(s): Takahashi, T., Yoshida, T., Harada, K., Miyagi, T., Hashimoto, K., Hide, I., Tanaka, S., Irifune, M. and Sakai, N.
  • Journal Title: PLos One Volume: 15 Issue: 11 Pages: e0242349-e0242349
  • DOI: 10.1371/journal.pone.0242349
  • Peer Reviewed / Open Access
• [Journal Article] Zonisamide can ameliorate the voltage-dependence alteration of the T-type calcium channel CaV3.1 caused by a mutationresponsible for spinocerebellar ataxia (2020)
  • Author(s): N. Hara, H. Morino, Y. Matsuda, K. Satoh, K. Hashimoto, H. Maruyama, H. Kawakami
  • Journal Title: Molecular Brain Volume: 13 Issue: 1 Pages: 163-163
  • DOI: 10.1186/s13041-020-00700-7
  • Peer Reviewed / Open Access
• [Journal Article] 神経細胞のresonance特性に関わるイオンチャネル (2020)
  • Author(s): 橋本浩一
  • Journal Title: BRAIN and NERVE Volume: 72 Pages: 1183-1194
• [Journal Article] Mechanisms for the resonant property in rodent neurons. (2019)
  • Author(s): Kouichi Hashimoto
  • Journal Title: Neurosci. Res. Volume: - Pages: 5-13
  • DOI: 10.1016/j.neures.2019.12.013
  • Peer Reviewed
• [Journal Article] mGluR1 in cerebellar Purkinje cells is essential for the formation but not expression of associative eyeblink memory (2019)
  • Author(s): Nakao Harumi、Kishimoto Yasushi、Hashimoto Kouichi、Kitamura Kazuo、Yamasaki Miwako、Nakao Kazuki、Watanabe Masahiko、Kano Masanobu、Kirino Yutaka、Aiba Atsu
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 7353-7353
  • DOI: 10.1038/s41598-019-43744-z
  • Peer Reviewed / Open Access
• [Journal Article] Microglia permit climbing fiber elimination by promoting GABAergic inhibition in the developing cerebellum (2018)
  • Author(s): Nakayama Hisako、Abe Manabu、Morimoto Chie、Iida Tadatsune、Okabe Shigeo、Sakimura Kenji、Hashimoto Kouichi
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 2830-2830
  • DOI: 10.1038/s41467-018-05100-z
  • Peer Reviewed / Open Access
• [Journal Article] The anatomical pathway from the mesodiencephalic junction to the inferior olive relays perioral sensory signals to the cerebellum in the mouse. (2018)
  • Author(s): Kubo, R., Aiba, A., Hashimoto, K.
  • Journal Title: Journal of Physiology (London) Volume: 596 Issue: 16 Pages: 3775-3791
  • DOI: 10.1113/jp275836
  • Peer Reviewed / Open Access
• [Journal Article] Glutamate transporter GLAST controls synaptic wrapping by Bergmann glia and ensures proper wiring of Purkinje cells. (2017)
  • Author(s): Miyazaki T, Yamasaki M, Hashimoto K, Kohda K, Yuzaki M, Shimamoto K, Tanaka K, Kano M, Watanabe M.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 114(28) Issue: 28 Pages: 7438-7443
  • DOI: 10.1073/pnas.1617330114
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV mice. (2017)
  • Author(s): Nakai N, Nagano M, Saitow F, Watanabe Y, Kawamura Y, Kawamoto A, Tamada K, Mizuma H, Onoe H, Watanabe Y, Monai H, Hirase H, Nakatani J, Inagaki H, Kawada T, Miyazaki T, Watanabe M, Sato Y, Okabe S, Kitamura K, Kano M, Hashimoto K, Suzuki H, Takumi T.
  • Journal Title: Sci Adv. Volume: 3(6) Issue: 6
  • DOI: 10.1126/sciadv.1603001
  • Peer Reviewed / Open Access
• [Presentation] Functional roles of Kv11 voltage-dependent K+ channels on the resonant property in neurons. (2020)
  • Author(s): Matsuoka T, Yamasaki M, Abe M, Matsuda Y, Morino H, Kawakami H, Sakimura K, Watanabe M, Hashimoto K.
  • Organizer: 第43回日本神経科学大会
• [Presentation] 体性感覚の小脳へのsimple spikeを介した信号伝達経路 (2020)
  • Author(s): 久保怜香、橋本浩一
  • Organizer: 第２５回グリアクラブ
• [Presentation] 下オリーブ核のオシレーションの発生機序 (2019)
  • Author(s): 橋本浩一
  • Organizer: 第34回 日本大脳基底核研究会
  • Invited
• [Presentation] 神経細胞のresonance特性におけるKv11チャネルの関与 (2019)
  • Author(s): 松岡 利典, 山崎 美和子, 阿部 学, 松田 由喜子, 森野 豊之, 川上 秀史 , 崎村 建司, 渡辺 雅彦, 橋本 浩一
  • Organizer: 次世代脳プロジェクト冬のシンポジウム2019
• [Presentation] Degeneration of cerebellar Purkinje cells in the knock-in mice harbouring SCA42 mutation (2019)
  • Author(s): Matsuda Y, Morino H, Kurashige T, Nakayama H, Matsuoka T, Sotomaru Y, Hashimoto K, Kawakami H.
  • Organizer: 第42回日本神経科学大会
• [Presentation] The perioral sensory signaling pathway for complex spike generation in cerebellar Purkinje cells (2019)
  • Author(s): Kubo R, Aiba A, Hashimoto K
  • Organizer: 9th FAOPS
  • Int'l Joint Research
• [Presentation] The model mouse of spinocerebellar ataxia 42 harbouring a missense mutation of Cacna1g (2018)
  • Author(s): Matsuda Y, Morino Y, Kurashige T, Nakayama H, Matsuoka T, Sotomaru Y, Hashimoto K, Kawakami H
  • Organizer: 第41回日本神経科学大会
• [Presentation] Perioral sensory signals are transmitted to the cerebellum via the anatomical pathway from mesodiencephalic junction to the inferior olive (2018)
  • Author(s): Kubo R, Aiba A, Hashimoto K
  • Organizer: 第41回日本神経科学大会
• [Presentation] マウスヒゲ触覚信号はarea parafascicularis prerubralisから下オリーブ核への経路を経て小脳に伝達される (2018)
  • Author(s): 久保怜香、饗場篤、橋本浩一
  • Organizer: 第70回日本生理学会中国四国地方会
• [Presentation] ミクログリア依存的な生後発達期神経回路再編成の解析 (2018)
  • Author(s): 橋本浩一
  • Organizer: 生理学研究所研究会「シナプス・神経回路機能の時空間制御」
• [Presentation] Anatomical pathway for perioral sensory signals to the inferior olive in the mouse. (2018)
  • Author(s): Kubo, R., Hashimoto, K.
  • Organizer: 第95回 日本生理学会大会
• [Presentation] マウスヒゲ領域から下オリーブ核に至る感覚経路の解析. (2017)
  • Author(s): 久保怜香、橋本浩一
  • Organizer: 生理学研究所研究会「シナプス・神経回路機能の時空間制御」
• [Presentation] Microglia Dependent Development of Neuronal Circuits in the Cerebellum. (2017)
  • Author(s): Nakayama, H., Abe, M., Morimoto, M., Sakimura, K., Hashimoto, K.
  • Organizer: 第40回 日本神経科学学会大会
• [Presentation] Activation of mTORC1 signaling in cerebellar Purkinje cells causes cell death and hypertrophy of Purkinje cells. (2017)
  • Author(s): Sakai, Y., Kassai, H., Nakayama, H., Nakao, K., Maeda, T., Hashimoto, K., Kano, M., Aiba, A.
  • Organizer: 第40回 日本神経科学学会大会
• [Remarks] 広島大学 大学院医系科学研究科 神経生理学
  • URL: https://physiol2.hiroshima-u.ac.jp/
• [Remarks] https://home.hiroshima-u.ac.jp/physiol2/
• [Remarks] 広島大学 医系科学研究科 神経生理学
  • URL: https://home.hiroshima-u.ac.jp/physiol2/index.html
• [Remarks]
  • URL: http://home.hiroshima-u.ac.jp/physiol2/