The recovery of standing and locomotion after spinal cord injury does not require task-specific training

Abstract

After complete spinal cord injury, mammals, including mice, rats and cats, recover hindlimb locomotion with treadmill training. The premise is that sensory cues consistent with locomotion reorganize spinal sensorimotor circuits. Here, we show that hindlimb standing and locomotion recover after spinal transection in cats without task-specific training. Spinal-transected cats recovered full weight bearing standing and locomotion after five weeks of rhythmic manual stimulation of triceps surae muscles (non-specific training) and without any intervention. Moreover, cats modulated locomotor speed and performed split-belt locomotion six weeks after spinal transection, functions that were not trained or tested in the weeks prior. This indicates that spinal networks controlling standing and locomotion and their interactions with sensory feedback from the limbs remain largely intact after complete spinal cord injury. We conclude that standing and locomotor recovery is due to the return of neuronal excitability within spinal sensorimotor circuits that do not require task-specific activity-dependent plasticity.

Data availability

A source data file has been provided with the article.

Article and author information

Author details

  1. Jonathan Harnie

    Department of Pharmacology-Physiology, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Adam Doelman

    Department of Pharmacology-Physiology, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Emmanuelle de Vette

    Department of Pharmacology-Physiology, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Johannie Audet

    Department of Pharmacology-Physiology, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Etienne Desrochers

    Department of Pharmacology-Physiology, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Nathalie Gaudreault

    School of Rehabilitation, Université de Sherbrooke, Sherbrooke, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Alain Frigon

    Department of Pharmacology-Physiology, Université de Sherbrooke, Sherbrooke, Canada
    For correspondence
    Alain.Frigon@USherbrooke.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9259-2706

Funding

Canadian Institutes of Health Research (PJT-156296)

  • Alain Frigon

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

Reviewing Editor

  1. Jan-Marino Ramirez, Seattle Children's Research Institute, United States

Ethics

Animal experimentation: All procedures were approved by the Animal Care Committee of the Université de Sherbrooke and were in accordance with policies and directives of the Canadian Council on Animal Care (Protocol 442-18). Twelve adult cats (> 1 year of age at time of experimentation), 5 males and 7 females, weighing between 3.6 kg and 4.7 kg were used in the present study. Our study followed the ARRIVE guidelines for animal studies (Kilkenny et al. 2010).

Version history

  1. Received: July 11, 2019
  2. Accepted: December 8, 2019
  3. Accepted Manuscript published: December 11, 2019 (version 1)
  4. Version of Record published: December 20, 2019 (version 2)

Copyright

© 2019, Harnie 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.

Metrics

  • 5,609
    Page views
  • 421
    Downloads
  • 20
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Jonathan Harnie
  2. Adam Doelman
  3. Emmanuelle de Vette
  4. Johannie Audet
  5. Etienne Desrochers
  6. Nathalie Gaudreault
  7. Alain Frigon
(2019)
The recovery of standing and locomotion after spinal cord injury does not require task-specific training
eLife 8:e50134.
https://doi.org/10.7554/eLife.50134

Share this article

https://doi.org/10.7554/eLife.50134

Further reading

    1. Developmental Biology
    2. Neuroscience
    Kristine B Walhovd, Stine K Krogsrud ... Didac Vidal-Pineiro
    Research Article

    Human fetal development has been associated with brain health at later stages. It is unknown whether growth in utero, as indexed by birth weight (BW), relates consistently to lifespan brain characteristics and changes, and to what extent these influences are of a genetic or environmental nature. Here we show remarkably stable and lifelong positive associations between BW and cortical surface area and volume across and within developmental, aging and lifespan longitudinal samples (N = 5794, 4–82 y of age, w/386 monozygotic twins, followed for up to 8.3 y w/12,088 brain MRIs). In contrast, no consistent effect of BW on brain changes was observed. Partly environmental effects were indicated by analysis of twin BW discordance. In conclusion, the influence of prenatal growth on cortical topography is stable and reliable through the lifespan. This early-life factor appears to influence the brain by association of brain reserve, rather than brain maintenance. Thus, fetal influences appear omnipresent in the spacetime of the human brain throughout the human lifespan. Optimizing fetal growth may increase brain reserve for life, also in aging.

    1. Cell Biology
    2. Neuroscience
    Marcos Moreno-Aguilera, Alba M Neher ... Carme Gallego
    Research Article

    Alternative RNA splicing is an essential and dynamic process in neuronal differentiation and synapse maturation, and dysregulation of this process has been associated with neurodegenerative diseases. Recent studies have revealed the importance of RNA-binding proteins in the regulation of neuronal splicing programs. However, the molecular mechanisms involved in the control of these splicing regulators are still unclear. Here we show that KIS, a kinase upregulated in the developmental brain, imposes a genome-wide alteration in exon usage during neuronal differentiation in mice. KIS contains a protein-recognition domain common to spliceosomal components and phosphorylates PTBP2, counteracting the role of this splicing factor in exon exclusion. At the molecular level, phosphorylation of unstructured domains within PTBP2 causes its dissociation from two co-regulators, Matrin3 and hnRNPM, and hinders the RNA-binding capability of the complex. Furthermore, KIS and PTBP2 display strong and opposing functional interactions in synaptic spine emergence and maturation. Taken together, our data uncover a post-translational control of splicing regulators that link transcriptional and alternative exon usage programs in neuronal development.