Spatiotemporal correlation of spinal network dynamics underlying spasms in chronic spinalized mice
- Karolinska Institutet, Sweden
- Karolinska Institute, Sweden
- 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
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
- 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
- Received: November 5, 2016
- Accepted: January 27, 2017
- Accepted Manuscript published: February 13, 2017 (version 1)
- Version of Record published: March 1, 2017 (version 2)
- 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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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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