Spinal microcircuits comprising dI3 interneurons are necessary for motor functional recovery following spinal cord transection

  1. Tuan V Bui
  2. Nicolas Stifani
  3. Turgay Akay
  4. Robert M Brownstone  Is a corresponding author
  1. University of Ottawa, Canada
  2. Dalhousie University, Canada
  3. University College London, Canada

Abstract

The spinal cord has the capacity to coordinate motor activities such as locomotion. Following spinal transection, functional activity can be regained, to a degree, following motor training. To identify microcircuits involved in this recovery, we studied a population of mouse spinal interneurons known to receive direct afferent inputs and project to intermediate and ventral regions of the spinal cord. We demonstrate that while dI3 interneurons are not necessary for normal locomotor activity, locomotor circuits rhythmically inhibit them and dI3 interneurons can activate these circuits. Removing dI3 interneurons from spinal microcircuits by eliminating their synaptic transmission left locomotion more or less unchanged, but abolished functional recovery, indicating that dI3 interneurons are a necessary cellular substrate for motor system plasticity following transection. We suggest that dI3 interneurons compare inputs from locomotor circuits with sensory afferent inputs to compute sensory prediction errors that then modify locomotor circuits to effect motor recovery.

Article and author information

Author details

  1. Tuan V Bui

    Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Nicolas Stifani

    Department of Medical Neuroscience, Dalhousie University, Halifax, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8584-9561
  3. Turgay Akay

    Department of Medical Neuroscience, Dalhousie University, Halifax, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Robert M Brownstone

    Dalhousie University, University College London, Halifax, Canada
    For correspondence
    R.Brownstone@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5135-2725

Funding

Canadian Institutes of Health Research (Operating grant, FRN 79413)

  • Robert M Brownstone

Nova Scotia Health Research Foundation (Post-doctoral fellowship)

  • Tuan V Bui

Natural Sciences and Engineering Research Council of Canada (Discovery grant, RGPIN-2015-06403)

  • Tuan V Bui

Canada Research Chairs (Research Chair)

  • Robert M Brownstone

Canadian Institutes of Health Research (Fellowship)

  • Tuan V Bui

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 animal procedures were approved by the University Committee on Laboratory Animals of Dalhousie University (protocol 13-143) and conform to the guidelines put forth by the Canadian Council for Animal Care.

Reviewing Editor

  1. Ole Kiehn, Karolinska Institutet, Sweden

Publication history

  1. Received: September 21, 2016
  2. Accepted: December 12, 2016
  3. Accepted Manuscript published: December 15, 2016 (version 1)
  4. Accepted Manuscript updated: December 22, 2016 (version 2)
  5. Version of Record published: January 6, 2017 (version 3)

Copyright

© 2016, Bui 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. Tuan V Bui
  2. Nicolas Stifani
  3. Turgay Akay
  4. Robert M Brownstone
(2016)
Spinal microcircuits comprising dI3 interneurons are necessary for motor functional recovery following spinal cord transection
eLife 5:e21715.
https://doi.org/10.7554/eLife.21715
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