Spatiotemporal correlation of spinal network dynamics underlying spasms in chronic spinalized mice

  1. Carmelo Bellardita  Is a corresponding author
  2. Vittorio Caggiano
  3. Roberto Leiras
  4. Vanessa Caldeira
  5. Andrea Fuchs
  6. Julien Bouvier
  7. Peter Löw
  8. Ole Kiehn  Is a corresponding author
  1. Karolinska Institutet, Sweden
  2. Karolinska Institute, Sweden
  3. Paris Saclay Institute of Neuroscience, UMR9197, CNRS, Universite Paris-Sud, France

Abstract

Spasms after spinal cord injury (SCI) are debilitating involuntary muscle contractions that have been associated with increased motor neuron excitability and decreased inhibition. However, whether spasms involve activation of premotor spinal excitatory neuronal circuits is unknown. Here we use mouse genetics, electrophysiology, imaging and optogenetics to directly target major classes of spinal interneurons as well as motor neurons during spasms in a mouse model of chronic SCI. We find that assemblies of excitatory spinal interneurons are recruited by sensory input into functional circuits to generate persistent neural activity, which interacts with both the graded expression of plateau potentials in motor neurons to generate spasms, and inhibitory interneurons to curtail them. Our study reveals hitherto unrecognized neuronal mechanisms for the generation of persistent neural activity under pathophysiological conditions, opening up new targets for treatment of muscle spasms after SCI.

Article and author information

Author details

  1. Carmelo Bellardita

    Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
    For correspondence
    carmelo.bellardita@ki.se
    Competing interests
    No competing interests declared.
  2. Vittorio Caggiano

    Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  3. Roberto Leiras

    Neuroscience Department, Karolinska Institute, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  4. Vanessa Caldeira

    Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  5. Andrea Fuchs

    Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  6. Julien Bouvier

    Paris Saclay Institute of Neuroscience, UMR9197, CNRS, Universite Paris-Sud, Gif-sur-Yvette, France
    Competing interests
    No competing interests declared.
  7. Peter Löw

    Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  8. Ole Kiehn

    Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
    For correspondence
    Ole.Kiehn@ki.se
    Competing interests
    Ole Kiehn, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5954-469X

Funding

European Research Council (693038)

  • Ole Kiehn

National Institute of Neurological Disorders and Stroke (R01 NS090919)

  • Ole Kiehn

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

Reviewing Editor

  1. Ronald L Calabrese, Emory University, United States

Ethics

Animal experimentation: All surgical procedures and experimental manipulations were approved by the local ethical committee and the Swedish Animal Welfare Agency and included in the ethical permit N. 29/2014.

Version history

  1. Received: November 5, 2016
  2. Accepted: January 27, 2017
  3. Accepted Manuscript published: February 13, 2017 (version 1)
  4. Version of Record published: March 1, 2017 (version 2)
  5. Version of Record updated: April 16, 2018 (version 3)

Copyright

© 2017, Bellardita 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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  1. Carmelo Bellardita
  2. Vittorio Caggiano
  3. Roberto Leiras
  4. Vanessa Caldeira
  5. Andrea Fuchs
  6. Julien Bouvier
  7. Peter Löw
  8. Ole Kiehn
(2017)
Spatiotemporal correlation of spinal network dynamics underlying spasms in chronic spinalized mice
eLife 6:e23011.
https://doi.org/10.7554/eLife.23011

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https://doi.org/10.7554/eLife.23011