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REM sleep selectively prunes and maintains new synapses in development and learning

Nature Neuroscience volume 20, pages 427437 (2017) | Download Citation

Abstract

The functions and underlying mechanisms of rapid eye movement (REM) sleep remain unclear. Here we show that REM sleep prunes newly formed postsynaptic dendritic spines of layer 5 pyramidal neurons in the mouse motor cortex during development and motor learning. This REM sleep-dependent elimination of new spines facilitates subsequent spine formation during development and when a new motor task is learned, indicating a role for REM sleep in pruning to balance the number of new spines formed over time. Moreover, REM sleep also strengthens and maintains newly formed spines, which are critical for neuronal circuit development and behavioral improvement after learning. We further show that dendritic calcium spikes arising during REM sleep are important for pruning and strengthening new spines. Together, these findings indicate that REM sleep has multifaceted functions in brain development, learning and memory consolidation by selectively eliminating and maintaining newly formed synapses via dendritic calcium spike-dependent mechanisms.

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Acknowledgements

We thank J. Cichon for technical help and all the members of the Gan laboratory for comments on the manuscript. This study was supported by funding from the NIH (R01 NS047325 and R01 MH111486 to W.-B.G., R01 GM107469 and R21 AG048410 to G.Y.), by the National Natural Science Foundation of China (81100839 to W.L.) and by Shenzhen Science and Technology Innovation Funds (GJHS20120628101219327, JC201105170726A, JCYJ20160428154351820, JSGG20140703163838793, ZDSYS201504301539161 and KQTD2015032709315529 to W.L. and L.M.).

Author information

Author notes

    • Wei Li
    •  & Lei Ma

    These authors contributed equally to this work.

Affiliations

  1. Drug Discovery Center, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, China.

    • Wei Li
    • , Lei Ma
    •  & Wen-Biao Gan
  2. Skirball Institute, Department of Neuroscience and Physiology, New York University School of Medicine, New York, New York, USA.

    • Wei Li
    • , Lei Ma
    •  & Wen-Biao Gan
  3. Department of Anesthesiology, New York University School of Medicine, New York, New York, USA.

    • Guang Yang

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Contributions

W.L. and L.M. contributed equally to this work. G.Y. and W.-B.G. initiated the project. W.L., L.M., G.Y. and W.-B.G. designed the experiments. W.L. and L.M. performed the experiments and analyzed the data with help from W.-B.G. W.-B.G. is a full-time faculty member at New York University School of Medicine and supervised the project as a visiting professor at Peking University Shenzhen Graduate School. W.L., L.M. and W.-B.G. prepared the manuscript with input from G.Y.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Wen-Biao Gan.

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    Supplementary Text and figures

    Supplementary Figures 1–15 and Supplementary Tables 1–6

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Videos

  1. 1.

    Ca2+ imaging of apical tuft dendrites of L5 pyramidal neurons expressing the genetically encoded calcium indicator GCaMP6s in the motor cortex under various brain states.

    Two-photon imaging of dendritic Ca2+ was performed through a thinned skull window over the motor cortex. The video showed dendritic Ca2+ spikes over a period of 1 minute for each brain state (quiet, running, NREM and REM sleep) and Ca2+fluorescence traces were shown in Fig. 5b and Supplementary Fig. 9a.

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DOI

https://doi.org/10.1038/nn.4479

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