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

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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.

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Tuan V Bui

Brain and Mind Research Institute, University of Ottawa, Ottawa, Canada

Competing interests
The authors declare that no competing interests exist.
Nicolas Stifani

Department of Medical Neuroscience, Dalhousie University, Halifax, Canada

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8584-9561
Turgay Akay

Department of Medical Neuroscience, Dalhousie University, Halifax, Canada

Competing interests
The authors declare that no competing interests exist.
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.

"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.

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.