Single neuron discrimination for refining neural circuits(Fostering Joint International Research)

• Project/Area Number: 15KK0331
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Gunma University
• Principal Investigator: Kaneko Ryosuke 群馬大学, 大学院医学系研究科, 助教 (40390695)
• Project Period (FY): 2016 – 2019
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
• Keywords: プロトカドヘリン / 小脳 / 運動学習 / 遺伝子改変マウス / オランダ / 神経科学 / 回路形成 / 学習

Outline of Final Research Achievements

In this study, the mouse cerebellum was used as a model system to verify the hypothesis that two neurons expressing the same Pcdh wire each other and make neural circuits. We found that Pcdh deficiency caused (i) abnormal cerebellar neural circuits in cerebellum and (ii) motor learning deficits. These results indicate that Pcdh is involved in the formation of functional neuronal circuits in the cerebellum. Furthermore, we have generated a Pcdh-expression reporter mouse, which will contribute to directly verify the hypothesis in the near future.

Academic Significance and Societal Importance of the Research Achievements

本研究により、小脳の機能的神経回路形成にPcdhが関与することが明らかとなった。小脳は運動学習を制御することが知られていた。さらに、近年になって自閉症への関与も報告され、高度な精神機能への関与も明らかとなった。従って、本研究を発展させることで、運動学習や高度な精神機能を担う新たな分子メカニズムの解明が予想される。将来的には、運動機能を向上させる新規な手法や自閉症の新たな治療法の開発に結びつく可能性がある。

Research Products

• [Int'l Joint Research] エラスムス医療センター(オランダ) (2016)
• [Journal Article] Pcdhb deficiency affects hippocampal CA1 ensemble activity and contextual fear discrimination (2020)
  • Author(s): Asai H, Ohkawa N, Saitoh Y, Ghandour K, Murayama E, Nishizono H, Matsuo M, Hirayama T, Kaneko R, Muramatsu S, Yagi T, Inokuchi K
  • Journal Title: Molecular Brai Volume: 13 Issue: 1 Pages: 7-7
  • DOI: 10.1186/s13041-020-0547-z
  • Peer Reviewed / Open Access
• [Journal Article] Genetic manipulation of autonomic nerve fiber innervation and activity and its effect on breast cancer progression (2019)
  • Author(s): Kamiya Atsunori、Hayama Yohsuke、Kato Shigeki、Shimomura Akihiko、Shimomura Takushi、Irie Katsumasa、Kaneko Ryosuke、Yanagawa Yuchio、Kobayashi Kazuto、Ochiya Takahiro
  • Journal Title: Nature Neuroscience Volume: 22 Issue: 8 Pages: 1289-1305
  • DOI: 10.1038/s41593-019-0430-3
  • Peer Reviewed
• [Journal Article] Analysis of the neuronal network of the medullary respiratory center in transgenic rats expressing archaerhodopsin-3 in Phox2b-expressing cells. (2019)
  • Author(s): Ikeda K, Kaneko R, Yanagawa Y, Ogawa M, Kobayashi K, Arata S, Kawakami K, Onimaru H.
  • Journal Title: Brain Res Bull. Volume: 144 Pages: 39-45
  • DOI: 10.1016/j.brainresbull.2018.11.005
  • Peer Reviewed
• [Journal Article] Freezing sperm in short straws reduces storage space and allows transport in dry ice (2018)
  • Author(s): Kaneko R, Kakinuma T, Sato S, Jinno-Oue A.
  • Journal Title: Journal of Reproduction and Development Volume: 64 Issue: 6 Pages: 541-545
  • DOI: 10.1262/jrd.2018-100
  • NAID: 130007530500
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed / Open Access
• [Journal Article] Targeted expression of step-function opsins in transgenic rats for optogenetic studies (2018)
  • Author(s): Igarashi Hiroyuki、Ikeda Keiko、Onimaru Hiroshi、Kaneko Ryosuke、Koizumi Kyo、Beppu Kaoru、Nishizawa Kayo、Takahashi Yukari、Kato Fusao、Matsui Ko、Kobayashi Kazuto、Yanagawa Yuchio、Muramatsu Shin-Ichi、Ishizuka Toru、Yawo Hiromu
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 5435-5435
  • DOI: 10.1038/s41598-018-23810-8
  • Peer Reviewed / Open Access
• [Journal Article] Maternal prolactin during late pregnancy is important in generating nurturing behavior in the offspring (2017)
  • Author(s): Sairenji Taku James、Ikezawa Jun、Kaneko Ryosuke、Masuda Shinnosuke、Uchida Kaoru、Takanashi Yurie、Masuda Hiroko、Sairenji Tomoko、Amano Izuki、Takatsuru Yusuke、Sayama Kazutoshi、Haglund Kaisa、Dikic Ivan、Koibuchi Noriyuki、Shimokawa Noriaki
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 114 Issue: 49 Pages: 13042-13047
  • DOI: 10.1073/pnas.1621196114
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Inhibitory neuron-specific Cre-dependent red fluorescent labeling using VGAT BAC-based transgenic mouse lines with identified transgene integration sites (2017)
  • Author(s): Kaneko Ryosuke、Takatsuru Yusuke、Morita Ayako、Amano Izuki、Haijima Asahi、Imayoshi Itaru、Tamamaki Nobuaki、Koibuchi Noriyuki、Watanabe Masahiko、Yanagawa Yuchio
  • Journal Title: Journal of Comparative Neurology Volume: 526 Issue: 3 Pages: 373-396
  • DOI: 10.1002/cne.24343
  • Peer Reviewed
• [Journal Article] Glycine release from astrocytes via functional reversal of GlyT1. (2017)
  • Author(s): Shibasaki K, Hosoi N, Kaneko R, Ishizaki Y, Yamada K
  • Journal Title: J. Neurochem. Volume: 140 Issue: 3 Pages: 395-403
  • DOI: 10.1111/jnc.13741
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Distinct and Cooperative Functions for the Protocadherin-alfa, -beta and -ganma Clusters in Neuronal Survival and Axon Targeting. (2016)
  • Author(s): Hasegawa S, Kumagai M, Hagiwara M, Nishimaru H, Hirano K, Kaneko R, Okayama A, Hirayama T, Sanbo M, Hirabayashi M, Watanabe M, Hirabayashi T, Yagi T
  • Journal Title: Front Mol Neurosci, Volume: 9 Pages: 155-155
  • DOI: 10.3389/fnmol.2016.00155
  • Peer Reviewed / Open Access
• [Journal Article] Establishment of high reciprocal connectivity between clonal cortical neurons is regulated by the Dnmt3b DNA methyltransferase and clustered protocadherins. (2016)
  • Author(s): Tarusawa E, Sanbo M, Okayama A, Miyashita T, Kitsukawa T, Hirayama T, Hirabayashi T, Hasegawa S, Kaneko R, Toyoda S, Kobayashi T, Kato-Itoh M, Nakauchi H, Hirabayashi M, Yagi T, Yoshimura Y.
  • Journal Title: BMC Biol. Volume: 14 Pages: 103-103
  • Peer Reviewed / Open Access
• [Journal Article] Unique pH dynamics in GABAergic synaptic vesicles illuminates the mechanism and kinetics of GABA loading. (2016)
  • Author(s): Egashira Y, Takase M, Watanabe S, Ishida J, Fukamizu A, Kaneko R, Yanagawa Y, Takamori S.
  • Journal Title: Proc Natl Acad Sci USA Volume: 113 Issue: 38 Pages: 10702-10707
  • DOI: 10.1073/pnas.1604527113
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A Novel Reporter Rat Strain That Conditionally Expresses the Bright Red Fluorescent Protein tdTomato. (2016)
  • Author(s): Igarashi H, Koizumi K, Kaneko R, Ikeda K, Egawa R, Yanagawa Y, Muramatsu S, Onimaru H, Ishizuka T, Yawo H.
  • Journal Title: PLoS One. Volume: 11 Issue: 5 Pages: e0155687-e0155687
  • DOI: 10.1371/journal.pone.0155687
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Transgenic rat model of childhood-onset dermatitis by overexpressing telomerase reverse transcriptase (TERT) (2016)
  • Author(s): Kaneko R, Sato A, Hamada S, Yagi T, Ohsawa I, Ohtsuki M, Kobayashi E, Hirabayashi M, and Murakami T
  • Journal Title: Transgenic Research Volume: 17 Feb Issue: 4 Pages: 1-12
  • DOI: 10.1007/s11248-016-9939-3
  • Peer Reviewed / Open Access
• [Journal Article] Regulation of human subcutaneous adipocyte differentiation by EID1. (2016)
  • Author(s): Vargas D, Shimokawa N, Kaneko R, Rosales W, Parra A, Castellanos Á, Koibuchi N, Lizcano F.
  • Journal Title: J Mol Endocrinol. Volume: 56 Issue: 2 Pages: 113-122
  • DOI: 10.1530/jme-15-0148
  • Peer Reviewed / Int'l Joint Research
• [Presentation] クラスター型プロトカドヘリンによる小脳プルキンエ細胞の配置制御 (2019)
  • Author(s): 金子涼輔、柳川右千夫、八木 健
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] ニューロンIDの可視化：クラスター型プロトカドヘリンの発現解析 (2019)
  • Author(s): 金子涼輔、阿部 学、高鶴裕介、井上(上野) 由紀子、渡辺雅彦、崎村建司、柳川右千夫、八木 健
  • Organizer: NEURO2019（第42回日本神経科学大会、第62回日本神経化学会大会）
• [Presentation] Visualizing single-neuron identity specified by Pcdh-b cluster (2018)
  • Author(s): Ryosuke Kaneko, Manabu Abe, Yusuke Takatsuru, Yukiko U. Inoue, Masahiko Watanabe, Kenji Sakimura, Yuchio Yanagawa, Takeshi Yagi
  • Organizer: 第41回日本神経科会大会
• [Presentation] How to modulate individuality: Involvement of expressional dynamism of Pcdh (2018)
  • Author(s): Ryosuke Kaneko
  • Organizer: 「個性」創発脳 第１回国際シンポジウム
  • Int'l Joint Research
• [Presentation] ニューロンIDの可視化 ～クラスター型プロトカドヘリンの発現解析～ (2017)
  • Author(s): 金子涼輔、阿部 学、高鶴裕介、渡辺雅彦、崎村建司、柳川右千夫、八木 健
  • Organizer: ConBio2017
• [Presentation] ニューロンIDの可視化 ～クラスター型プロトカドヘリンの発現解析～ (2017)
  • Author(s): 金子涼輔、阿部 学、高鶴裕介、渡辺雅彦、崎村建司、柳川右千夫、八木 健
  • Organizer: 第40回日本神経科会大会
• [Presentation] ニューロンIDの可視化：クラスター型プロトカドヘリンの発現解析 (2016)
  • Author(s): 金子涼輔、阿部 学、高鶴裕介、渡辺雅彦、崎村建司、柳川右千夫、八木 健
  • Organizer: 第39回日本神経科会大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-07-20
• [Remarks] 群馬大学大学院医学系研究科附属生物資源センター
  • URL: http://doujitsu.dept.med.gunma-u.ac.jp/cms/?page_id=16