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Closed-loop auditory stimulation method to modulate sleep slow waves and motor learning performance in rats

  1. Carlos G Moreira
  2. Christian R Baumann
  3. Maurizio Scandella
  4. Sergio I Nemirovsky
  5. Sven Leach
  6. Reto Huber
  7. Daniela Noain  Is a corresponding author
  1. University Hospital Zurich, Switzerland
  2. University of Buenos Aires, Argentina
  3. University Children's Hospital Zurich, Switzerland
  4. Childrens University Hospital Zurich, Switzerland
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Cite this article as: eLife 2021;10:e68043 doi: 10.7554/eLife.68043

Abstract

Slow waves and cognitive output have been modulated in humans by phase-targeted auditory stimulation. However, to advance its technical development and further our understanding, implementation of the method in animal models is indispensable. Here, we report the successful employment of slow waves' phase-targeted closed-loop auditory stimulation (CLAS) in rats. To validate this new tool both conceptually and functionally, we tested the effects of up- and down‑phase CLAS on proportions and spectral characteristics of sleep, and on learning performance in the single-pellet reaching task, respectively. Without affecting 24-h sleep-wake behavior, CLAS specifically altered delta (slow waves) and sigma (sleep spindles) power persistently over chronic periods of stimulation. While up-phase CLAS does not elicit a significant change in behavioral performance, down-phase CLAS exerted a detrimental effect on overall engagement and success rate in the behavioral test. Overall CLAS-dependent spectral changes were positively correlated with learning performance. Altogether, our results provide proof-of-principle evidence that phase-targeted CLAS of slow waves in rodents is efficient, safe and stable over chronic experimental periods, enabling the use of this high‑specificity tool for basic and preclinical translational sleep research.

Data availability

The .edf files containing EEG/EMG signal (BL and M-T1-4), the corresponding labels detailing vigilance states (4s resolution), the temporal flags of the auditory triggers, and the counts from the single-pellet reaching task are publicly available in Dryad (doi:10.5061/dryad.bvq83bk99). All figures accompanied by an Excel file containing the numerical data and statistical analyses are provided with this submission as well as in the Dryad repository.

The following data sets were generated

Article and author information

Author details

  1. Carlos G Moreira

    Neurology, University Hospital Zurich, Schlieren, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Christian R Baumann

    Department of Neurology, University Hospital Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3417-1978
  3. Maurizio Scandella

    Neurology, University Hospital Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Sergio I Nemirovsky

    Institute of Biological Chemistry, School of Exact and Natural Sciences (IQUIBICEN)., University of Buenos Aires, Buenos Aires, Argentina
    Competing interests
    The authors declare that no competing interests exist.
  5. Sven Leach

    Child Development Center, University Children's Hospital Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Reto Huber

    Child Development Center, Childrens University Hospital Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  7. Daniela Noain

    Neurology, University Hospital Zurich, Schlieren, Switzerland
    For correspondence
    daniela.noain@usz.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5482-7933

Funding

Swiss National Science Foundation (163056 and 188790)

  • Christian R Baumann

Synapsis Foundation for Alzheimer's Research

  • Daniela Noain

Neuroscience Center Zurich, University of Zurich (Rahn and Bodmer donation)

  • Daniela Noain

Armin and Jeannine Kurz Stiftung

  • Daniela Noain

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures were approved by the veterinary office of the Canton Zurich under license ZH231/2015.

Reviewing Editor

  1. Denise Cai, Icahn School of Medicine at Mount Sinai, United States

Publication history

  1. Received: March 4, 2021
  2. Accepted: September 29, 2021
  3. Accepted Manuscript published: October 6, 2021 (version 1)

Copyright

© 2021, Moreira et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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