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

Abstract
Article and author information
Metrics

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

Carmelo Bellardita

Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

For correspondence
carmelo.bellardita@ki.se

Competing interests
No competing interests declared.
Vittorio Caggiano

Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

Competing interests
No competing interests declared.
Roberto Leiras

Neuroscience Department, Karolinska Institute, Stockholm, Sweden

Competing interests
No competing interests declared.
Vanessa Caldeira

Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

Competing interests
No competing interests declared.
Andrea Fuchs

Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

Competing interests
No competing interests declared.
Julien Bouvier

Paris Saclay Institute of Neuroscience, UMR9197, CNRS, Universite Paris-Sud, Gif-sur-Yvette, France

Competing interests
No competing interests declared.
Peter Löw

Mammalian locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden

Competing interests
No competing interests declared.
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.

"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.

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.

Copyright

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.