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Sharp wave ripples during learning stabilize the hippocampal spatial map

Nature Neuroscience volume 20, pages 845853 (2017) | Download Citation

Abstract

Cognitive representation of the environment requires a stable hippocampal map, but the mechanisms maintaining a given map are unknown. Because sharp wave-ripples (SPW-R) orchestrate both retrospective and prospective spatial information, we hypothesized that disrupting neuronal activity during SPW-Rs affects spatial representation. Mice learned new sets of three goal locations daily in a multiwell maze. We used closed-loop SPW-R detection at goal locations to trigger optogenetic silencing of a subset of CA1 pyramidal neurons. Control place cells (nonsilenced or silenced outside SPW-Rs) largely maintained the location of their place fields after learning and showed increased spatial information content. In contrast, the place fields of SPW-R-silenced place cells remapped, and their spatial information remained unaltered. SPW-R silencing did not impact the firing rates or proportions of place cells. These results suggest that interference with SPW-R-associated activity during learning prevents stabilization and refinement of hippocampal maps.

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Acknowledgements

We thank N. Chenouard, G. Girardeau, L. Sjulson, A. Peyrache and all members of the lab for invaluable discussions, advice and comments on the manuscript. This work was supported by NIH grants MH107396, MH54671, U01NS090583, the Simons Foundation, and the G. Harold and Leila Y. Mathers Foundation. L.R. was supported by the NIH grant K99NS094735 and the Bettencourt Schueller Foundation. E.S. was supported by the Rothschild Foundation, Human Frontiers in Science Program LT-000346/2009-l, Machiah Foundation 20090098 and ERC-2015-StG 679253. B.H. was supported by the National Natural Science Foundation of China (grant no. 31471050).

Author information

Author notes

    • Bo Hu
    •  & Ronny Eichler

    Present addresses: Third Military Medical University, College of Basic Medical Sciences, Department of Physiology, Chongqing, China (B.H.) and Radboud University Nijmegen, Donders Centre for Neuroscience, Departments of Neuroinformatics and Neurophysiology, Nijmegen, Netherlands (R.E.).

Affiliations

  1. New York University Neuroscience Institute, New York University, New York, New York, USA.

    • Lisa Roux
    • , Bo Hu
    • , Ronny Eichler
    • , Eran Stark
    •  & György Buzsáki
  2. Tel Aviv University, Sackler Faculty of Medicine and Sagol School of Neuroscience, Department of Physiology and Pharmacology, Tel Aviv, Israel.

    • Eran Stark
  3. Department of Neurology, Medical Center, New York University, New York, New York, USA.

    • György Buzsáki
  4. Center for Neural Science, New York University, New York, New York, USA.

    • György Buzsáki

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Contributions

L.R. and G.B. designed the experiments and wrote the manuscript; L.R. performed the experiments and analyzed the data; B.H. performed experiments; R.E. provided the software for online tracking of mouse position; and E.S. provided assistance for data analysis.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to György Buzsáki.

Integrated supplementary information

Supplementary figures

  1. 1.

    Information on transgenic mouse models and their recording and optogenetic equipment.

  2. 2.

    Results for the four CamKII-cre::Arch mice without the PV-cre::ChR2 mouse.

  3. 3.

    Details of unit classification.

  4. 4.

    Relationship between the light-response index of individual place cells and their firing rate change during the SPW-Rs between task and postexploration epochs.

  5. 5.

    Indirect silencing of pyramidal cells by optogenetic activation of inhibitory PV cells in the PV-cre::ChR2 mouse.

  6. 6.

    Quantification of SPW-R detection and silencing.

  7. 7.

    Behavioral performance in sessions with ripple-locked and ripple-delayed stimulation conditions.

  8. 8.

    Place field overlap calculation method.

  9. 9.

    Comparison of place cells recorded in ripple-locked and ripple-delayed categories supports a role for SPW-Rs in place field stabilization and refinement.

  10. 10.

    Silencing pyramidal cells during SPW-Rs does not affect their firing rates or ability to code for space.

  11. 11.

    Place cell remapping is not related to measures of recording instability or to the probability of firing at goal locations before learning.

  12. 12.

    SPW-R silenced place cell ensembles show nonstabilized spatial representation as compared to simultaneously recorded Control ensembles after controlling for ensemble size.

  13. 13.

    Data from the cued version of cheeseboard maze task.

  14. 14.

    Changes in activity during slow-wave sleep SPW-Rs are comparable across experimental groups and do not predict the degree of place cell remapping.

  15. 15.

    Goal location representation before and after learning.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–15 and Supplementary Table 1

  2. 2.

    Supplementary Methods Checklist

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DOI

https://doi.org/10.1038/nn.4543

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