Addition of angled rungs to the horizontal ladder walking task for more sensitive probing of sensorimotor changes.

One method for the evaluation of sensorimotor therapeutic interventions, the horizontal ladder walking task, analyzes locomotor changes that may occur after disease, injury, or by external manipulation. Although this task is well suited for detection of large effects, it may overlook smaller changes...

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Main Authors: Jaclyn T Eisdorfer, Michael A Phelan, Kathleen M Keefe, Morgan M Rollins, Thomas J Campion, Kaitlyn M Rauscher, Hannah Sobotka-Briner, Mollie Senior, Gabrielle Gordon, George M Smith, Andrew J Spence
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2021-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0246298
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author Jaclyn T Eisdorfer
Michael A Phelan
Kathleen M Keefe
Morgan M Rollins
Thomas J Campion
Kaitlyn M Rauscher
Hannah Sobotka-Briner
Mollie Senior
Gabrielle Gordon
George M Smith
Andrew J Spence
author_facet Jaclyn T Eisdorfer
Michael A Phelan
Kathleen M Keefe
Morgan M Rollins
Thomas J Campion
Kaitlyn M Rauscher
Hannah Sobotka-Briner
Mollie Senior
Gabrielle Gordon
George M Smith
Andrew J Spence
author_sort Jaclyn T Eisdorfer
collection DOAJ
description One method for the evaluation of sensorimotor therapeutic interventions, the horizontal ladder walking task, analyzes locomotor changes that may occur after disease, injury, or by external manipulation. Although this task is well suited for detection of large effects, it may overlook smaller changes. The inability to detect small effect sizes may be due to a neural compensatory mechanism known as "cross limb transfer", or the contribution of the contralateral limb to estimate an injured or perturbed limb's position. The robust transfer of compensation from the contralateral limb may obscure subtle locomotor outcomes that are evoked by clinically relevant therapies, in the early onset of disease, or between higher levels of recovery. Here, we propose angled rungs as a novel modification to the horizontal ladder walking task. Easily-adjustable angled rungs force rats to locomote across a different locomotion path for each hindlimb and may therefore make information from the contralateral limb less useful. Using hM3Dq (excitatory) Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) expressed in large diameter peripheral afferents of the hindlimb in the intact animal, we characterized the sensitivity of our design to detect stepping differences by comparing locomotor changes observed on angled rungs to those observed on a standard horizontal ladder. On our novel asymmetrical ladder, activation of DREADDs resulted in significant differences in rung misses (p = 0.000011) and weight-supporting events (p = 0.049). By comparison, on a standard ladder, we did not observe differences in these parameters (p = 0.86 and p = 0.98, respectively). Additionally, no locomotor differences were detected in baseline and inactivated DREADDs trials when we compared ladder types, suggesting that the angled rungs do not change animal gait behavior unless intervention or injury is introduced. Significant changes observed with angled rungs may demonstrate more sensitive probing of locomotor changes due to the decoupling of cross limb transfer.
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spelling doaj.art-b298cf8997354942aa562ab859139e3f2022-12-22T02:54:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01162e024629810.1371/journal.pone.0246298Addition of angled rungs to the horizontal ladder walking task for more sensitive probing of sensorimotor changes.Jaclyn T EisdorferMichael A PhelanKathleen M KeefeMorgan M RollinsThomas J CampionKaitlyn M RauscherHannah Sobotka-BrinerMollie SeniorGabrielle GordonGeorge M SmithAndrew J SpenceOne method for the evaluation of sensorimotor therapeutic interventions, the horizontal ladder walking task, analyzes locomotor changes that may occur after disease, injury, or by external manipulation. Although this task is well suited for detection of large effects, it may overlook smaller changes. The inability to detect small effect sizes may be due to a neural compensatory mechanism known as "cross limb transfer", or the contribution of the contralateral limb to estimate an injured or perturbed limb's position. The robust transfer of compensation from the contralateral limb may obscure subtle locomotor outcomes that are evoked by clinically relevant therapies, in the early onset of disease, or between higher levels of recovery. Here, we propose angled rungs as a novel modification to the horizontal ladder walking task. Easily-adjustable angled rungs force rats to locomote across a different locomotion path for each hindlimb and may therefore make information from the contralateral limb less useful. Using hM3Dq (excitatory) Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) expressed in large diameter peripheral afferents of the hindlimb in the intact animal, we characterized the sensitivity of our design to detect stepping differences by comparing locomotor changes observed on angled rungs to those observed on a standard horizontal ladder. On our novel asymmetrical ladder, activation of DREADDs resulted in significant differences in rung misses (p = 0.000011) and weight-supporting events (p = 0.049). By comparison, on a standard ladder, we did not observe differences in these parameters (p = 0.86 and p = 0.98, respectively). Additionally, no locomotor differences were detected in baseline and inactivated DREADDs trials when we compared ladder types, suggesting that the angled rungs do not change animal gait behavior unless intervention or injury is introduced. Significant changes observed with angled rungs may demonstrate more sensitive probing of locomotor changes due to the decoupling of cross limb transfer.https://doi.org/10.1371/journal.pone.0246298
spellingShingle Jaclyn T Eisdorfer
Michael A Phelan
Kathleen M Keefe
Morgan M Rollins
Thomas J Campion
Kaitlyn M Rauscher
Hannah Sobotka-Briner
Mollie Senior
Gabrielle Gordon
George M Smith
Andrew J Spence
Addition of angled rungs to the horizontal ladder walking task for more sensitive probing of sensorimotor changes.
PLoS ONE
title Addition of angled rungs to the horizontal ladder walking task for more sensitive probing of sensorimotor changes.
title_full Addition of angled rungs to the horizontal ladder walking task for more sensitive probing of sensorimotor changes.
title_fullStr Addition of angled rungs to the horizontal ladder walking task for more sensitive probing of sensorimotor changes.
title_full_unstemmed Addition of angled rungs to the horizontal ladder walking task for more sensitive probing of sensorimotor changes.
title_short Addition of angled rungs to the horizontal ladder walking task for more sensitive probing of sensorimotor changes.
title_sort addition of angled rungs to the horizontal ladder walking task for more sensitive probing of sensorimotor changes
url https://doi.org/10.1371/journal.pone.0246298
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