Activity-dependent mechanisms regulating dendriticmorphology and function

2012 Fiscal Year Final Research Report

• Project/Area Number: 20670002
• Research Category: Grant-in-Aid for Young Scientists (S)
• Allocation Type: Single-year Grants
• Research Field: Neuroscience in general
• Research Institution: The University of Tokyo
• Principal Investigator: BITO Haruhiko 東京大学, 大学院・医学系研究科, 准教授 (00291964)
• Project Period (FY): 2008 – 2012
• Keywords: カルシウム / リン酸化 / 突起伸展 / シナプスから核へのシグナリング

Research Abstract

Molecular mechanisms underlying experience-dependent information processing and storage have remained elusive. Here, in this research program, we have uncovered novel molecular insights on (1)the role of CaMKK-CaMK cascade in neurite morphogenesis, (2) the signaling cascade that triggers new gene expression upon receipt of synaptic activity, and (3)a new inverse synaptic tagging mechanism that mediates specific forms of synaptic modulation upon activity-dependent gene expression. These findings shed new lights on the machinery that transforms and stores information about previous experience within the neural circuits.

Research Products

• [Journal Article] Nonlinear Decoding and Asymmetric Representation of Neuronal Input Information by CaMKIIα and Calcineurin (2013)
  • Author(s): Fujii H, Inoue M, Okuno H, Sano Y, Takemoto-Kimura S, Kitamura K, Kano M, Bito H
  • Journal Title: Cell Reports Volume: 3 Pages: 978-987
  • DOI: doi:10.1016/j.celrep.2013.03.033
  • Peer Reviewed
• [Journal Article] Executive function deficits andsocial-behavioral abnormality in miceexposed to a low dose of dioxin in utero and via lactation (2012)
  • Author(s): Endo T, Kakeyama M, Uemura Y, Haijima A, Okuno H, Bito H, Tohyama C
  • Journal Title: PLoS ONE Volume: 7 Pages: e50741
  • DOI: doi:10.1371/journal.pone.0050741
  • Peer Reviewed
• [Journal Article] An inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKII ss (2012)
  • Author(s): Okuno H, Akashi K, Ishii Y, Yagishita-Kyo N, Suzuki K, Nonaka M, Kawashima T, Fujii H, Takemoto-Kimura S, Abe M, Natsume R, Chowdhury S, Sakimura K, Worley PF, Bito H
  • Journal Title: Cell Volume: 149 Pages: 886-898
  • Peer Reviewed
• [Journal Article] Schema-dependent gene activation and memory encoding in neocortex (2011)
  • Author(s): Tse D, Takeuchi T, Kakeyama M, Kajii Y, Okuno H, Tohyama C, Bito H, MorrisRGM
  • Journal Title: Science Volume: 333 Pages: 891-895
  • Peer Reviewed
• [Journal Article] Ca2+ signaling coordinates the formation and the morphological maturation of neuronal circuits and synapses: an essential role for excitation-morphogenesis coupling via CaM kinases (2010)
  • Author(s): Takemoto-Kimura S, Suzuki K, Kamijo S, Ageta-Ishihara N, Fujii H, Okuno H, BitoH
  • Journal Title: Eur. J. Neurosci Volume: 32 Pages: 224-230
  • Peer Reviewed
• [Journal Article] The chemical biology of synapses and neuronal circuits (2010)
  • Author(s): Bito H
  • Journal Title: Nature Chem. Biol Volume: 6 Pages: 560-563
  • Peer Reviewed
• [Journal Article] Widespread transcription at neuronal activity-regulated enhancers (2010)
  • Author(s): Kim TK, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J, Harmin DA, Laptewicz M, Barbara-Haley K, Kuersten S, Markenscoff-Papadimitriou E, Kuhl D, Bito H, Worley PF, Kreiman G,Greenberg ME
  • Journal Title: Nature Volume: 465 Pages: 182-187
  • Peer Reviewed
• [Journal Article] Synaptic tagging and capture: differential role of distinct calcium/calmodulin kinases in protein synthesis-dependent long-term potentiation (2010)
  • Author(s): Redondo RL, Okuno H, Spooner PA, Frenguelli BG, Bito H, Morris RGM
  • Journal Title: J. Neurosci Volume: 30 Pages: 4981-4989
  • Peer Reviewed
• [Journal Article] Regulation of cortical axon growth by a GABA-driven Ca2+/ calmodulin-dependent protein kinase cascade (2009)
  • Author(s): Ageta-Ishihara N, Takemoto-Kimura S, Nonaka M, Adachi-Morishima A, Suzuki K, Kamijo S, Fujii H, Mano T, Blaeser F, Chatila TA, Mizuno H, Hirano T, Tagawa Y, Okuno H, Bito H
  • Journal Title: J. Neurosci Volume: 29 Pages: 13720 -13729
  • Peer Reviewed
• [Journal Article] A synaptic activity-responsive element in the Arc/Arg3.1 promoter essential for synapse-to-nucleus signaling in activated neurons (2009)
  • Author(s): Kawashima T, Okuno H, Nonaka M, Adachi-Morishima A, Kyo N, Okamura M, Takemoto-Kimura S, Worley PF, Bito H
  • Journal Title: Proc. Natl. Acad. Sci. USA Volume: 106 Pages: 316-321
  • Peer Reviewed
• [Presentation] The role of Arc in inverse tagging of inactive synapses (2013)
  • Author(s): Bito H
  • Organizer: 25th Winter Conference on Neural Plasticity
  • Place of Presentation: Curacao, Netherlands.
  • Year and Date: 2013-02-10
• [Presentation] New roles of CaMKII in information storage and processing (2013)
  • Author(s): Bito H
  • Organizer: 46thWinter Conference on Brain Research
  • Place of Presentation: Breckenridge, Colorado, USA.
  • Year and Date: 2013-01-29
• [Presentation] CREB, Arc and Long-Term MemoryFormation (2012)
  • Author(s): Nonaka M, Fukushima H, Sasaki K, Kawashima T, Okuno H, Kida S, Bito H
  • Organizer: 22nd Neuropharmacology Conference 2012
  • Place of Presentation: Hilton Riverside, New Orleans, Louisiana, USA
  • Year and Date: 2012-10-10
• [Presentation] CREB regulation and long-termmemory (2011)
  • Author(s): Bito H
  • Organizer: Joint Meeting of the KoreanSociety for Brain and Neural Science-Asian Molecular and Cellular Cognition Society
  • Place of Presentation: Seoul National University, Seoul, Korea
  • Year and Date: 2011-09-19
• [Presentation] New roles for CaMK signaling in development and plasticity (2011)
  • Author(s): Bito H
  • Organizer: Gordon Research Conferences "ExcitatorySynapses & Brain Function"
  • Place of Presentation: Stonehill College, Easton, Massachusetts, USA.
  • Year and Date: 2011-06-30
• [Presentation] Dual FRET-based analysis of biochemical computation performed by neuronal Ca2+ signaling (2011)
  • Author(s): Bito H
  • Organizer: The 23^<rd> WinterConference on Neural Plasticity
  • Place of Presentation: Moorea, French Polynesia.
  • Year and Date: 2011-02-15
• [Presentation] Dual FRET-based analysis of biochemical computation performed by neuronal Ca^2+ signaling processes (2010)
  • Author(s): Fujii H, Bito H
  • Organizer: The 2^<nd> International Symposium on Frontiers ofNeurophotonics
  • Place of Presentation: Quebec, Canada
  • Year and Date: 2010-09-22
• [Presentation] CaM kinase signaling in neuronal microdomains (2010)
  • Author(s): Bito H
  • Organizer: The 13^<th> International Membrane Research Forum/The 6^<th> iCeMS InternationalSymposium Featuring Nano- Meso Membrane Mechanisms
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-01-27
• [Presentation] Synaptic activity-dependent regulation of plasticity-related gene Arc (2009)
  • Author(s): Bito H
  • Organizer: 4^<th> International Conference of Neurons and Brain Diseases
  • Place of Presentation: Toronto,Canada
  • Year and Date: 2009-07-23
• [Presentation] Regulation of excitation- morphogenesis coupling by CaMKK/CaMKI cascades (2008)
  • Author(s): Bito H
  • Organizer: 3^<rd> International Conference on Neurons and Brain Diseases
  • Place of Presentation: Seoul, Korea.
  • Year and Date: 2008-08-05
• [Book] 活動依存的な遺伝子発現誘導・ 突起伸展機構.In ブレインサイレンス・レビュー (2013)
  • Author(s): 尾藤晴彦
  • Total Pages: 155-168
  • Publisher: 廣川信隆 編、クバプロ
• [Book] "CREB" in "Encyclo-pedia of Signaling Molecules" (2012)
  • Author(s): Yagishita-Kyo N, Inoue M, Nonaka M, Okuno H, Bito H.
  • Total Pages: 454-458
  • Publisher: Springer
• [Book] 神経細胞内ではたら くシグナル伝達 in シリーズ脳科学 5 分子・細胞・シナプスからみる脳 甘利 (2008)
  • Author(s): 尾藤晴彦 、有賀 純
  • Publisher: 俊一監修 ,古市貞一 編.東京大学 出版会
• [Book] Activity-dependent gene regulation: Howdo synapses talk to the nucleus and fine-tune neuronal outputs? in "Molecular Pain" (2008)
  • Author(s): Bito H, Takemoto-Kimura S, Okuno H
  • Total Pages: 207-217
  • Publisher: M. Zhuo ed. Springer
• [Remarks]
  • URL: http://www.neurochem.m.u-tokyo.ac.jp/
• [Patent(Industrial Property Rights)] 神経活動依存的プロモータ活性を有するDNA、及びこれを含むベクター (2012)
  • Inventor(s): 尾藤晴彦、奥野浩行、川島尚之
  • Industrial Property Rights Holder: 尾藤晴彦、奥野浩行、川島尚之
  • Industrial Property Number: 特願2012-205892
  • Filing Date: 2012-09-19
• [Patent(Industrial Property Rights)] 画像処理装置及びプログラム (2012)
  • Inventor(s): 尾藤晴彦、川島尚之
  • Industrial Property Rights Holder: 尾藤晴彦、川島尚之
  • Industrial Property Number: 特願2012-170548
  • Filing Date: 2012-07-31
• [Patent(Industrial Property Rights)] CaMKII阻害ペプチドおよびこれを含有するCaMKII阻害剤 (2012)
  • Inventor(s): 西川喜代孝、高橋美帆、西村浩輝、高柳広、尾藤晴彦
  • Industrial Property Rights Holder: 西川喜代孝、高橋美帆、西村浩輝、高柳広、尾藤晴彦
  • Patent Publication Number: 特開2012-158525
  • Filing Date: 2012-08-23