大脳皮質神経回路の生後発達に関わるメカニズムの解明

• Project Area: Neural Diversity and Neocortical Organization
• Project/Area Number: 25123716
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Hiroshima University
• Principal Investigator: 橋本 浩一 広島大学, 医歯薬保健学研究院, 教授 (00303272)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000); Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
• Keywords: retrosplenial cortex / シナプス / 生後発達 / 脳神経 / シグナル伝達 / 神経科学

Outline of Annual Research Achievements

大脳皮質神経回路の生後発達過程を解析する為、脳梁－皮質神経細胞間の興奮性シナプス伝達の生後発達変化に着目した。生後2-17日齢のC57BL6マウス脳梁膨大後部皮質（retrosplenial cortex）から冠状断切片を作成し、神経細胞からWhole-cell recordingを行った。脳梁膨大後部皮質の様々な層の神経細胞からパッチクランプ記録を行い、電気生理学的な性質の解析を進めた。その結果、皮質Ⅱ層と、Ⅴ-Ⅵ層に錐体細胞様の電気生理学的特性を示す神経細胞が存在することが分かった。また皮質Ⅲ-Ⅳ層には、バースト状の発火特性を示す神経細胞が存在することが分かった。
さらに、脳梁に設置した刺激電極から電気刺激を行い、各層に存在する神経細胞に誘発される興奮性シナプス伝達を解析した。皮質Ⅲ-Ⅳ層の神経細胞には、脳梁刺激で興奮性シナプス応答は誘発されなかった。皮質Ⅴ－Ⅵ層の錐体細胞において刺激強度に応じたステップ状のシナプス応答を比較的安定に誘発できることが分かったため、生後日齢を変えて入力線維数の生後発達変化を解析した。その結果、一つのⅤ-Ⅵ層錐体細胞に入力する脳梁線維の本数は発達の過程で徐々に増加することが分かった。その後、入力線維の数が若干減少する時期が見られた。この結果は、retrosplenial cortexⅤ-Ⅵ層錐体細胞では、一旦過剰に作られたシナプスが刈り込まれる可能性を示唆する。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells. (2015)
  • Author(s): Muguruma K, et al.
  • Journal Title: Cell Reports Volume: 10 Issue: 4 Pages: 537-550
  • DOI: 10.1016/j.celrep.2014.12.051
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Global Scaling Down of Excitatory Postsynaptic Responses in Cerebellar Purkinje Cells Impairs Developmental Synapse Elimination. (2014)
  • Author(s): Kawata S, Miyazaki T, Yamazaki M, Mikuni T, Yamasaki M, Hashimoto K, Watanabe M, Sakimura K, Kano M.
  • Journal Title: Cell Rep. Volume: 8(4) Issue: 4 Pages: 1119-29
  • DOI: 10.1016/j.celrep.2014.07.014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Deficits in cerebellar plasticity and motor learning in a copy number variation mouse model of autism spectrum disorder. (2014)
  • Author(s): Pichon, C., Kloth, A. D., Grasselli, G., Titley, H. K., Nakayama, H., Hashimoto, K., Wan, V., Simmons, D. H., Eissa, T., Nakatani, J., Cherskov, A., Miyazaki, T., Watanabe, M., Takumi T., Kano, M., Wang S. S-H. and Hansel, C.
  • Journal Title: Nat. Commun. Volume: 5 Issue: 1 Pages: 5586-5586
  • DOI: 10.1038/ncomms6586
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The synaptic targeting of mGluR1 by its carboxyl-terminal domain Is crucial for cerebellar function (2014)
  • Author(s): Yoshiaki Ohtani, Mariko Miyata, Kouichi Hashimoto, Toshihide Tabata, Yasushi Kishimoto, Masahiro Fukaya, Daisuke Kase, Hidetoshi Kassai, Kazuki Nakao, Tatsumi Hirata, Masahiko Watanabe, Masanobu Kano, Atsu Aiba
  • Journal Title: Journal of Neuroscience Volume: 34 Issue: 7 Pages: 2702-2712
  • DOI: 10.1523/jneurosci.3542-13.2014
  • Peer Reviewed
• [Journal Article] Spike timing-dependent selective strengthening of single climbing fibre inputs to Purkinje cells during cerebellar development. (2013)
  • Author(s): Yoshinobu Kawamura, Hisako Nakayama, Kouichi Hashimoto, Kenji Sakimura, Kazuo Kitamura and Masanobu Kano.
  • Journal Title: Nat Commun. Volume: 4 Issue: 1 Pages: 2732-2732
  • DOI: 10.1038/ncomms3732
  • Peer Reviewed
• [Journal Article] Synapse elimination in the developing cerebellum. (2013)
  • Author(s): Hashimoto K, Kano M.
  • Journal Title: Cell Mol Life Sci Volume: 24 Issue: 24 Pages: 4667-4680
  • DOI: 10.1007/s00018-013-1405-2
  • Peer Reviewed
• [Journal Article] Calcium-dependent regulation of climbing fiber synapse elimination during postnatal cerebellar development. (2013)
  • Author(s): Kano M, Nakayama H, Hashimoto K, Kitamura K, Sakimura K, Watanabe M
  • Journal Title: J. Physiol. Volume: 591 Issue: 13 Pages: 3151-3158
  • DOI: 10.1113/jphysiol.2012.248252
  • Peer Reviewed
• [Presentation] Type1 metabotropic glutamate receptor regulates experience-dependent maintenance of mature synaptic connectivity in the visual thalamus. (2015)
  • Author(s): Narushima, M., Uchigashima, M., Harada, T., Hashimoto K., Aiba, A., Watanabe, M., Miyata, M., Kano, M.
  • Organizer: 第92回日本生理学会大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] CDC42EP4/septin-based perisyanptic glial scaffold that facilitates glutamate clearance. (2015)
  • Author(s): Ageta-Ishida, N., Yamazaki, M., Konno, K., Nakayama, H., Abe, M., Hashimoto, K., Nishioka, T., Kaibuchi, K., Miyakawa, T., Hashimoto, K., Watanabe, M., Sakimura, K., Kinoshita, M.
  • Organizer: 第92回日本生理学会大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Analysis of spontaneous slow currents in the inferior olivary neurons (2015)
  • Author(s): Matsumoto Y., Nakayama, H., Hashimoto, K. .
  • Organizer: 第92回日本生理学会大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] The change of morphology and distributions of microglia in the postnatal developing mouse cerebellum. (2015)
  • Author(s): Morimoto C., Nakayama, H., Hashimoto, K.
  • Organizer: 第92回日本生理学会大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Deficits in cerebellar plasticity and motor learning in a copy number variation mouse model of autism spectrum disorder. (2014)
  • Author(s): Piochon, C., Simmons, D.H., Kloth, A.D., Grasselli, G., Titley, H.K., Nakayama, H., Hashimoto, K., Wan, V., Eissa, T., Nakatani, J., Cherskov, A., Miyazaki, T., Watanabe, M., Takumi, T., Kano, M., Wang, S.S.H., Hansel, C.
  • Organizer: Neuro 2014
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] CDC42EP4-septin complex in parasynaptic domains of Bergmann glia facilitates cerebellar motor learning via GLAST-mediated glutamate clearance from the parallel fiber-Purkinje cell synapses. (2014)
  • Author(s): Ageta-Ishida, N., Yamazaki, M., Konno, K., Nakayama, H., Abe, M., Miyakawa, T., Hashimoto, K., Watanabe, M., Sakimura, K., Kinoshita, M.
  • Organizer: Neuro 2014
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Molecular mechanism of sensory experience-dependent maintenance of neuronal circuits. (2014)
  • Author(s): Miyata, M., Narushima, M., Uchigashima, M., Hashimoto , K., Harada, T., Aiba, A., Watanabe, M., Kano, M.
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] CDC42EP4/septin-dependent localization of GLAST to parasynaptic domains of Bergmann glia facilitates glutamate clearance from the parallel fiber-Purkinje cell synapses and motor learning. (2014)
  • Author(s): Ageta-Ishida, N., Yamazaki, M., Konno, K., Nakayama, H., Abe, M., Hashimoto, K., Nishioka, T., Kaibuchi, K., Miyakawa, T., Hashimoto, K., Watanabe, M., Sakimura, K., Kinoshita, M.
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Stargazin（TARPγ-2）の欠損による小脳プルキンエ細胞でのカルシウムシグナルの減弱により登上線維刈り込みの後期過程が選択的に障害される
  • Author(s): 川田慎也、橋本浩一、三國貴康、山崎真弥、宮崎太輔、山崎美和子、渡辺雅彦、崎村建司、狩野方伸
  • Organizer: 第36回日本神経科学学会大会
  • Place of Presentation: 京都
• [Presentation] Selective strengthening of single climbing fiber inputs to Purkinje cells during postnatal cerebellar development In vivo.
  • Author(s): Kawamura, Y., Nakayama, H., Hashimoto, K., Sakimura, K., Kitamura, K. & Kano, M
  • Organizer: Annual meeting of the Society for Neuroscience
  • Place of Presentation: San Diego
• [Presentation] Global scaling-down of excitatory postsynaptic responses in cerebellar Purkinje cells specifically impairs the late phase of climbing fiber synapse elimination during postnatal development.
  • Author(s): Kawata, S., Miyazaki, T., Yamazaki, M., Mikuni, T., Yamasaki, M., Hashimoto, K., Watanabe, M., Sakimura, K. & Kano, M
  • Organizer: Annual meeting of the Society for Neuroscience
  • Place of Presentation: San Diego
• [Presentation] An autism-associated neuroligin-3 mutation impairs developmental synapse elimination in the cerebellum.
  • Author(s): Lai, E., Nakayama, H., Nakazawa, T., Tabuchi, K., Hashimoto, K. & Kano, M
  • Organizer: Annual meeting of the Society for Neuroscience
  • Place of Presentation: San Diego
• [Remarks]
  • URL: http://home.hiroshima-u.ac.jp/physiol2/
• [Remarks] 広島大学 神経生理学
  • URL: http://home.hiroshima-u.ac.jp/physiol2/