Silencing long-descending inter-enlargement propriospinal neurons improves hindlimb stepping after contusive spinal cord injuries
- University of Louisville, United States
Abstract
Spinal locomotor circuitry is comprised of rhythm generating centers, one for each limb, that are interconnected by local and long-distance propriospinal neurons thought to carry temporal information necessary for interlimb coordination and gait control. We showed previously that conditional silencing of the long ascending propriospinal neurons (LAPNs) that project from the lumbar to the cervical rhythmogenic centers (L1/L2 to C6), disrupts right-left alternation of both the forelimbs and hindlimbs without significantly disrupting other fundamental aspects of interlimb and speed-dependent coordination (Pocratsky et al., 2020). Subsequently, we showed that silencing the LAPNs after a moderate thoracic contusive spinal cord injury (SCI) resulted in better recovered locomotor function (Shepard et al., 2021). In this research advance, we focus on the descending equivalent to the LAPNs, the long descending propriospinal neurons (LDPNs) that have cell bodies at C6 and terminals at L2. We found that conditional silencing of the LDPNs in the intact adult rat resulted in disrupted alternation of each limb pair (forelimbs and hindlimbs) and after a thoracic contusion SCI significantly improved locomotor function. These observations lead us to speculate that the LAPNs and LDPNs have similar roles in the exchange of temporal information between the cervical and lumbar rhythm generating centers, but that the partial disruption of the pathway after SCI limits the independent function of the lumbar circuitry. Silencing the LAPNs or LDPNs effectively permits or frees-up the lumbar circuitry to function independently.
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All source data for the main figures have been provided.
Article and author information
Author details
Scott R Whittemore
Funding
National Institute of Neurological Disorders and Stroke (R01 NS112304-01)
- Scott R Whittemore
- David SK Magnuson
National Institute of Neurological Disorders and Stroke (R01 NS089324)
- Scott R Whittemore
- David SK Magnuson
National Institute of Neurological Disorders and Stroke (F31 NS116935)
- Brandon L Brown
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Christopher Cardozo, Icahn School of Medicine at Mount Sinai, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#19644) of the University of Louisville. All surgery was performed under ketamine/xylazine anesthesia supplemented with isoflurane, and every effort was made to minimize suffering.
Version history
- Received: August 30, 2022
- Preprint posted: September 1, 2022 (view preprint)
- Accepted: December 13, 2023
- Accepted Manuscript published: December 15, 2023 (version 1)
- Version of Record published: January 9, 2024 (version 2)
Copyright
© 2023, Shepard 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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Silencing long-descending inter-enlargement propriospinal neurons improves hindlimb stepping after contusive spinal cord injuries
eLife 12:e82944.
https://doi.org/10.7554/eLife.82944
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