Long Ascending Propriospinal Neurons Provide Task-Specific, Context-Driven Control of Interlimb Coordination

Pocratsky, Amanda M; Shepard, Courtney T; Morehouse, Johnny R.; Burke, Darlene A.; Riegler, Amberly S.; Hardin, Josiah T; Beare, Jason E.; Hainline, Casey; States, Gregory Jr; Whittemore, Scott R.; Magnuson, David S.K.

doi:10.2139/ssrn.3406385

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“…It is The copyright holder for this preprint this version posted May 19, 2021. ; https://doi.org/10.1101/2021.05.18.444653 doi: bioRxiv preprint 5 silencing did not affect the well-described, speed-dependent gait indices of swing time (Fig 1i,n), stance time (Fig 1j,o), stride time (Fig 1k,p), stride frequency (Fig 1l,q), or stride distance (Fig 1m,r). The excursion of the proximal limb angle remained unaffected by silencing, whereas there were slight, but significant effects on the excursion of the distal limb angle (Figure 1 -figure supplement 1h-j) (Pocratsky et al, 2020). These findings replicate our earlier observations and show that LAPNs secure interlimb coordination with little to no change in intralimb coordination or other fundamental gait characteristics in an otherwise intact rat.…”

Section: Resultssupporting

confidence: 88%

“…Immunohistochemistry to enhance eTeNT.EGFP revealed EGFP-positive fibers (putative axon terminals) surrounding neuronal processes in the caudal cervical enlargement (Fig 2l,m). Similar to uninjured histology (Pocratsky et In rostral lumbar spinal cord segments, eTeNT-EGFP-positive LAPN cell bodies colocalized with fluorescent Nissl-stained (NeuroTrace) neurons in the intermediate gray matter (Fig 2t-v) (Reed et al, 2006;Pocratsky et al, 2020). Isotype controls showed no immunoreactivity .…”

Section: Spared Lapns Express Synapse-silencing Etentegfp Chronicallymentioning

confidence: 65%

“…In our recent study focused on LAPN silencing in uninjured animals, the behavioral phenotype was strongly context-dependent, with disruptions to alternation occurring only during non-exploratory overground locomotion on a walking surface with good grip. Disruptions were insignificant during overground stepping on a slick surface, on a treadmill, or during exploratory-driven stepping (Pocratsky et al, 2020).…”

Section: Discussionmentioning

confidence: 92%

“…Virus production, characterization, and injections were done as described previously (Pocratsky et al, 2017a(Pocratsky et al, , 2017b(Pocratsky et al, , 2020.…”

Section: Intraspinal Injections Of Viral Vectors To Doubly Infect Lapnsmentioning

confidence: 99%

“…Acquisition and analysis of hindlimb kinematics were performed as previously described (Pocratsky et al, 2017a(Pocratsky et al, , 2020. Briefly, we digitized the movements of the hindlimb using the iliac crest, hip, ankle and toe from two sagittally oriented cameras.…”

Section: Hindlimb Kinematics and Intralimb Coordinationmentioning

confidence: 99%

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

Shepard

Pocratsky

Brown

et al. 2021

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Long ascending propriospinal neurons (LAPNs) are a subpopulation of spinal cord interneurons that directly connect the lumbar and cervical enlargements. In uninjured animals, conditionally silencing LAPNs resulted in 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 in the adult rat. Given their ventrolateral location in the spinal cord white matter, many LAPN axons likely remain intact following thoracic spinal cord injury (SCI), suggesting a potential role in the recovery of stepping. Thus, we hypothesized that silencing LAPNs after SCI would result in diminished hindlimb locomotor function. We found instead that silencing of spared LAPNs post-SCI restored the left-right hindlimb coordination associated with alternating gaits that was lost as a result of SCI. Several other fundamental characteristics of hindlimb stepping were also improved and the number of abnormal steps were reduced. However, hindlimb-forelimb coordination was not restored. These data suggest that the temporal information carried between the enlargements by the LAPNs after SCI may be detrimental to hindlimb locomotor function. These observations have implications for our understanding of the relationship between injury severity and functional outcome, for the efforts to develop neuro- and axo-protective therapeutic strategies, and also for the clinical study/implementation of spinal stimulation and neuromodulation.

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Section: Resultssupporting

confidence: 88%

Section: Spared Lapns Express Synapse-silencing Etentegfp Chronicallymentioning

confidence: 65%

Section: Discussionmentioning

confidence: 92%

“…Virus production, characterization, and injections were done as described previously (Pocratsky et al, 2017a(Pocratsky et al, , 2017b(Pocratsky et al, , 2020.…”

Section: Intraspinal Injections Of Viral Vectors To Doubly Infect Lapnsmentioning

confidence: 99%

Section: Hindlimb Kinematics and Intralimb Coordinationmentioning

confidence: 99%

See 3 more Smart Citations

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

Shepard

Pocratsky

Brown

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Long Ascending Propriospinal Neurons Provide Task-Specific, Context-Driven Control of Interlimb Coordination

Cited by 1 publication

References 0 publications

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

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

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