Analysis for heterosynaptic competition between parallel and climbing fiber in mature Purkinje cells

• Project/Area Number: 26460250
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Hokkaido University
• Principal Investigator: Miyazaki Taisuke 北海道大学, 医学研究科, 助教 (90374230)
• Research Collaborator: YAMASAKI MIWAKO 北海道大学, 医学研究科, 准教授 (10431305)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: プルキンエ細胞 / 登上線維 / 平行線維 / 電位依存性カルシウムチャネル / シナプス競合

Outline of Final Research Achievements

Purkinje cells receive two excitatory inputs, parallel fiber (PF) and climbing fiber (CF). This PC circuitry is established by heterosynaptic competition between PF and CF, fueled by glutamate receptor GluRδ2 and voltage-gated calcium ion channel Cav2.1, respectively. However, it has been unclear whether this heterosynaptic competition maintains PC circuitry in the adult cerebellum. To uncover this question, I investigated novel mouse line, in which Cav2.1 gene can be deleted in adult PCs by the drug-induced ablation system. In anatomical and electrophysiological investigation, inducible Cav2.1 ablation in the adult cerebellum caused motor discoordination and imbalance of heterosynaptic competiton with proximal expansion of PF territory. Therefore, Cav2.1 fuels CF inputs and balance heterosynaptic competition in the adult cerebellum. This result strongly suggests that the balance of heterosynaptic competition is essential for the cerebellar function.

Research Products

• [Journal Article] Ionic Basis for Membrane Potential Resonance in Neurons of the Inferior Olive. (2016)
  • Author(s): Matsumoto-Makidono, Y., Nakayama, H., Yamasaki, M., Miyazaki, T., Kobayashi, K., Watanabe, M., Kano, M., Sakimura, K., Hashimoto, K.
  • Journal Title: Cell Reports Volume: 16 Issue: 4 Pages: 994-1004
  • DOI: 10.1016/j.celrep.2016.06.053
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The active zone protein CAST regulates synaptic vesicle recycling and quantal size in the mouse hippocampus. (2016)
  • Author(s): Kobayashi S, Hida Y, Ishizaki H, Inoue E, Tanaka-Okamoto M, Yamasaki M, Miyazaki T, Masahiro F, Kitajima I, Takai Y, Watanabe M, Ohtsuka T, Manabe T
  • Journal Title: Eur J Neurosci. Volume: 44 Issue: 5 Pages: 2272-2284
  • DOI: 10.1111/ejn.13331
  • Peer Reviewed / Open Access
• [Journal Article] Medial septal GABAergic projection neurons promote object exploration behavior and Type 2 theta rhythm. (2016)
  • Author(s): Gangadharan G, Shin J, Kim S-W, Kim A, Paydar A, Kim D-S, Miyazaki T, Watanabe M, Yanagawa Y, Kim J, Kim Y-S, Kim D, Shin H-S.
  • Journal Title: Proc. Natl. Acad. Sci. USA, Volume: 113 Issue: 23 Pages: 6550-6555
  • DOI: 10.1073/pnas.1605019113
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Territories of heterologous inputs onto Purkinje cell dendrites are segregated by mGluR1-dependent parallel fiber synapse elimination (2016)
  • Author(s): Ichikawa R, Hashimoto K, Miyazaki T, Uchigashima M, Yamasaki M, Aiba A, Kano M, Watanabe M
  • Journal Title: Proc Natl Acad Sci U S A Volume: 113 (8) Issue: 8 Pages: 2282-7
  • DOI: 10.1073/pnas.1511513113
  • NAID: 120005828473
  • Peer Reviewed / Open Access
• [Journal Article] VGluT3-Expressing CCK-Positive Basket Cells Construct Invaginating Synapses Enriched with Endocannabinoid Signaling Proteins in Particular Cortical and Cortex-Like Amygdaloid Regions of Mouse Brains. (2015)
  • Author(s): Omiya Y, Uchigashima M, Konno K, Yamasaki M, Miyazaki T, Yoshida T, Kusumi I, Watanabe M.
  • Journal Title: J Neurosci. Volume: 35(10) Issue: 10 Pages: 4215-4228
  • DOI: 10.1523/jneurosci.4681-14.2015
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Structure-Function Relationships between Aldolase C/Zebrin II Expression and Complex Spike Synchrony in the Cerebellum. (2015)
  • Author(s): Tsutsumi S, Yamazaki M, Miyazaki T, Watanabe M, Sakimura K, Kano M, Kitamura K
  • Journal Title: J Neurosci. Volume: 35(2) Issue: 2 Pages: 843-52
  • DOI: 10.1523/jneurosci.2170-14.2015
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Chemical corrector treatment ameliorates increased seizure susceptibility in a mouse model of familial temporal lobe epilepsy. (2015)
  • Author(s): Yokoi N, Fukata Y, Kase D, Miyazaki T, Jaegle M, Ohkawa T, Takahashi N, Iwanari H, Mochizuki Y, Hamakubo T, Imoto K, Meijer D, Watanabe M, Fukata M
  • Journal Title: Nat Med Volume: 21 Issue: 1 Pages: 19-26
  • DOI: 10.1038/nm.3759
  • Peer Reviewed / 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] A new mouse allele of glutamate receptor delta 2 with cerebellar atrophy and progressive ataxia (2014)
  • Author(s): Miyoshi, Y., Yoshioka, Y., Suzuki, K., Miyazaki, T., Koura, M., Saigoh, K., Kajimura, N., Monobe,Y., Kusunoki, S., Matsuda, J., Watanabe, M. and Hayakawa, N.
  • Journal Title: PLoS ONE Volume: 9 (9) Issue: 9 Pages: 1-12
  • DOI: 10.1371/journal.pone.0107867
  • Peer Reviewed / Open Access
• [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] Neuron type- and input pathway-dependent expression of Slc4a10 in adult mouse brains. (2014)
  • Author(s): Song X, Yamasaki M, Miyazaki T, Konno K, Uchigashima M, Watanabe M
  • Journal Title: Eur J Neurosci, Volume: 40 Issue: 5 Pages: 2797-2810
  • DOI: 10.1111/ejn.12636
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Enriched Expression of GluD1 in Higher Brain Regions and Its Involvement in Parallel Fiber-Interneuron Synapse Formation in the Cerebellum. (2014)
  • Author(s): Konno K, Matsuda K, Nakamoto C, Uchigashima M, Miyazaki T, Yamasaki M, Sakimura K, Yuzaki M, Watanabe M.
  • Journal Title: J Neurosci. Volume: 34(22) Issue: 22 Pages: 7412-24
  • DOI: 10.1523/jneurosci.0628-14.2014
  • NAID: 120005537463
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Calcineurin B1 subunit is essential for climbing fiber mono-innervation and inhibitory synapse formation in cerebellar Purkinje cells (2017)
  • Author(s): Taisuke Miyazaki, Kenji Sakimura, Masahiko Watanabe
  • Organizer: 第122回日本解剖学会総会
  • Place of Presentation: 長崎大学坂本キャンパス（長崎県長崎市）
  • Year and Date: 2017-03-28
• [Presentation] Cav2.1 is indispensable to maintain wiring, survival, and compartmentalized expression in adult cerebellar Purkinje cells (2016)
  • Author(s): Taisuke Miyazaki, Miwako Yamasaki, Kenji Sakimura, Masahiko Watanabe
  • Organizer: 第39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: 2016-07-20
• [Presentation] Neuroanatomical properties of cerebellar interneuron Lugaro cells using with GFP–expressing transgenic mice line (2016)
  • Author(s): Taisuke Miyazaki, Kenji F. Tanaka, Masahiko Watanabe
  • Organizer: 第121回日本解剖学会総会・全国学術集会
  • Place of Presentation: ビッグパレットふくしま（福島県・郡山市）
  • Year and Date: 2016-03-28
• [Presentation] Morphological characteristics of cerebellar interneuron Lugaro cells using with GFP–expressing transgenic mice line (2015)
  • Author(s): Taisuke Miyazaki, Kenji F. Tanaka, Masahiko Watanabe
  • Organizer: Neuroscience 2015
  • Place of Presentation: McCormick Place (Chicago, IL)
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] プルキンエ細胞に発現するカルシニューリンCNB1サブユニットは小脳の興奮性および抑制性シナプス回路形成に重要である (2015)
  • Author(s): 宮崎 太輔, 崎村 建司, 渡辺 雅彦
  • Organizer: 第61回東北・北海道連合支部学術集会
  • Place of Presentation: 盛岡市観光文化交流センター (岩手県・盛岡市)
  • Year and Date: 2015-08-29
• [Presentation] プルキンエ細胞に発現するCNB1は小脳の興奮性および抑制性シナプス回路形成に重要である (2015)
  • Author(s): Taisuke Miyazaki, Kenji Sakimura , Masahiko Watanabe
  • Organizer: 第３８回日本神経科学大会
  • Place of Presentation: 神戸国際会議場 (兵庫県・神戸市)
  • Year and Date: 2015-07-28
• [Presentation] Calcineurin B1 subunit expressed in Purkinje cell is essential for the formation of excitatory and inhibitory cerebellar neuronal network. (2015)
  • Author(s): Taisuke Miyazaki, Kenji Sakimura , Masahiko Watanabe
  • Organizer: 第120回日本解剖学会総会・全国学術集会
  • 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] 蛍光タンパク発現モデルマウスを用いた小脳ルガロ細胞に関する形態学解析 (2014)
  • Author(s): 宮崎 太輔
  • Organizer: 日本顕微鏡学会第70回記念学術講演会
  • Place of Presentation: 幕張メッセ（千葉県・幕張市）
  • Year and Date: 2014-05-11 – 2014-05-13
• [Book] Immunocytochemistry and Related Techniques. Chapter 16. Combined immunocytochemistry and tracing of neural connections. (2015)
  • Author(s): Taisuke Miyazaki and Masahiko Watanabe
  • Total Pages: 14
  • Publisher: Humana Press.