Article | Published:

Labelling and optical erasure of synaptic memory traces in the motor cortex

Nature volume 525, pages 333338 (17 September 2015) | Download Citation

Abstract

Dendritic spines are the major loci of synaptic plasticity and are considered as possible structural correlates of memory. Nonetheless, systematic manipulation of specific subsets of spines in the cortex has been unattainable, and thus, the link between spines and memory has been correlational. We developed a novel synaptic optoprobe, AS-PaRac1 (activated synapse targeting photoactivatable Rac1), that can label recently potentiated spines specifically, and induce the selective shrinkage of AS-PaRac1-containing spines. In vivo imaging of AS-PaRac1 revealed that a motor learning task induced substantial synaptic remodelling in a small subset of neurons. The acquired motor learning was disrupted by the optical shrinkage of the potentiated spines, whereas it was not affected by the identical manipulation of spines evoked by a distinct motor task in the same cortical region. Taken together, our results demonstrate that a newly acquired motor skill depends on the formation of a task-specific dense synaptic ensemble.

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Acknowledgements

We thank H. Bito and H. Okuno for the generous gift of the Arc promoter; F. Murakami for the information about Arc 3′ UTR; M. Yuzaki, K. Inokuchi, and K. Fox for discussions. This research was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT, Japan; No. 2000009 to H.K. and No. 26221011 to H.K. and A.H.-T., No. 23689055 and No. 24116003 to A.H.-T.), the PRESTO program (JST) to A.H-T., the brain/MIND and SICP projects from Japan Agency for Medical Research and Development (AMED) to H.K., the National Institutes of Health grant GM102924 to K.M.H., NS071216 to Y.I.W. and the Research Grant from the Human Frontier Science Program to H.K., K.M.H. and B.K.

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Affiliations

  1. Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033

    • Akiko Hayashi-Takagi
    • , Sho Yagishita
    • , Mayumi Nakamura
    • , Fukutoshi Shirai
    •  & Haruo Kasai
  2. PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan

    • Akiko Hayashi-Takagi
  3. CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan

    • Sho Yagishita
    •  & Haruo Kasai
  4. Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, Connecticut 06032, USA

    • Yi I. Wu
  5. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA

    • Amanda L. Loshbaugh
    • , Brian Kuhlman
    •  & Klaus M. Hahn
  6. Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599, USA

    • Amanda L. Loshbaugh
    •  & Brian Kuhlman
  7. Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599, USA

    • Klaus M. Hahn

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Contributions

A.H.-T., S.Y., M.N., and F.S. conducted the experiments. Y.I.W., A.L.L., K.M.H., and B.K. provided technical support for the development of PaRac1. A.H.-T. and H.K. designed the study and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Akiko Hayashi-Takagi or Haruo Kasai.

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DOI

https://doi.org/10.1038/nature15257

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