Silencing long ascending propriospinal neurons after spinal cord injury improves hindlimb stepping in the adult rat

Long ascending propriospinal neurons (LAPNs) are a subpopulation of spinal cord interneurons that directly connect the lumbar and cervical enlargements. Previously we showed, in uninjured animals, that conditionally silencing LAPNs disrupted left-right coordination of the hindlimbs and forelimbs in...

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Autores principales:	Courtney T Shepard, Amanda M Pocratsky, Brandon L Brown, Morgan A Van Rijswijck, Rachel M Zalla, Darlene A Burke, Johnny R Morehouse, Amberley S Riegler, Scott R Whittemore, David SK Magnuson
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	spinal cord injury propriospinal neurons locomotion viral vector neuronal silencing Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/76d9111e10d94c34bf93f809c60aae3d
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spelling	oai:doaj.org-article:76d9111e10d94c34bf93f809c60aae3d2021-12-02T10:31:42ZSilencing long ascending propriospinal neurons after spinal cord injury improves hindlimb stepping in the adult rat10.7554/eLife.700582050-084Xe70058https://doaj.org/article/76d9111e10d94c34bf93f809c60aae3d2021-12-01T00:00:00Zhttps://elifesciences.org/articles/70058https://doaj.org/toc/2050-084XLong ascending propriospinal neurons (LAPNs) are a subpopulation of spinal cord interneurons that directly connect the lumbar and cervical enlargements. Previously we showed, in uninjured animals, that conditionally silencing LAPNs disrupted left-right coordination of the hindlimbs and forelimbs in a context-dependent manner, demonstrating that LAPNs secure alternation of the fore- and hindlimb pairs during overground stepping. Given the ventrolateral location of LAPN axons in the spinal cord white matter, many likely remain intact following incomplete, contusive, thoracic spinal cord injury (SCI), suggesting a potential role in the recovery of stepping. Thus, we hypothesized that silencing LAPNs after SCI would disrupt recovered locomotion. Instead, we found that silencing spared LAPNs post-SCI improved locomotor function, including paw placement order and timing, and a decrease in the number of dorsal steps. Silencing also restored left-right hindlimb coordination and normalized spatiotemporal features of gait such as stance and swing time. However, hindlimb-forelimb coordination was not restored. These data indicate that the temporal information carried between the spinal enlargements by the spared LAPNs post-SCI is detrimental to recovered hindlimb locomotor function. These findings are an illustration of a post-SCI neuroanatomical-functional paradox and have implications for the development of neuronal- and axonal-protective therapeutic strategies and the clinical study/implementation of neuromodulation strategies.Courtney T ShepardAmanda M PocratskyBrandon L BrownMorgan A Van RijswijckRachel M ZallaDarlene A BurkeJohnny R MorehouseAmberley S RieglerScott R WhittemoreDavid SK MagnusoneLife Sciences Publications Ltdarticlespinal cord injurypropriospinal neuronslocomotionviral vectorneuronal silencingMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	spinal cord injury propriospinal neurons locomotion viral vector neuronal silencing Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	spinal cord injury propriospinal neurons locomotion viral vector neuronal silencing Medicine R Science Q Biology (General) QH301-705.5 Courtney T Shepard Amanda M Pocratsky Brandon L Brown Morgan A Van Rijswijck Rachel M Zalla Darlene A Burke Johnny R Morehouse Amberley S Riegler Scott R Whittemore David SK Magnuson Silencing long ascending propriospinal neurons after spinal cord injury improves hindlimb stepping in the adult rat
description	Long ascending propriospinal neurons (LAPNs) are a subpopulation of spinal cord interneurons that directly connect the lumbar and cervical enlargements. Previously we showed, in uninjured animals, that conditionally silencing LAPNs disrupted left-right coordination of the hindlimbs and forelimbs in a context-dependent manner, demonstrating that LAPNs secure alternation of the fore- and hindlimb pairs during overground stepping. Given the ventrolateral location of LAPN axons in the spinal cord white matter, many likely remain intact following incomplete, contusive, thoracic spinal cord injury (SCI), suggesting a potential role in the recovery of stepping. Thus, we hypothesized that silencing LAPNs after SCI would disrupt recovered locomotion. Instead, we found that silencing spared LAPNs post-SCI improved locomotor function, including paw placement order and timing, and a decrease in the number of dorsal steps. Silencing also restored left-right hindlimb coordination and normalized spatiotemporal features of gait such as stance and swing time. However, hindlimb-forelimb coordination was not restored. These data indicate that the temporal information carried between the spinal enlargements by the spared LAPNs post-SCI is detrimental to recovered hindlimb locomotor function. These findings are an illustration of a post-SCI neuroanatomical-functional paradox and have implications for the development of neuronal- and axonal-protective therapeutic strategies and the clinical study/implementation of neuromodulation strategies.
format	article
author	Courtney T Shepard Amanda M Pocratsky Brandon L Brown Morgan A Van Rijswijck Rachel M Zalla Darlene A Burke Johnny R Morehouse Amberley S Riegler Scott R Whittemore David SK Magnuson
author_facet	Courtney T Shepard Amanda M Pocratsky Brandon L Brown Morgan A Van Rijswijck Rachel M Zalla Darlene A Burke Johnny R Morehouse Amberley S Riegler Scott R Whittemore David SK Magnuson
author_sort	Courtney T Shepard
title	Silencing long ascending propriospinal neurons after spinal cord injury improves hindlimb stepping in the adult rat
title_short	Silencing long ascending propriospinal neurons after spinal cord injury improves hindlimb stepping in the adult rat
title_full	Silencing long ascending propriospinal neurons after spinal cord injury improves hindlimb stepping in the adult rat
title_fullStr	Silencing long ascending propriospinal neurons after spinal cord injury improves hindlimb stepping in the adult rat
title_full_unstemmed	Silencing long ascending propriospinal neurons after spinal cord injury improves hindlimb stepping in the adult rat
title_sort	silencing long ascending propriospinal neurons after spinal cord injury improves hindlimb stepping in the adult rat
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/76d9111e10d94c34bf93f809c60aae3d
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Silencing long ascending propriospinal neurons after spinal cord injury improves hindlimb stepping in the adult rat

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