Header

UZH-Logo

Maintenance Infos

Undirected compensatory plasticity contributes to neuronal dysfunction after severe spinal cord injury


Beauparlant, Janine; van den Brand, Rubia; Barraud, Quentin; Friedli, Lucia; Musienko, Pavel; Dietz, Volker; Courtine, Grégoire (2013). Undirected compensatory plasticity contributes to neuronal dysfunction after severe spinal cord injury. Brain, 136(Pt 11):3347-3361.

Abstract

Severe spinal cord injury in humans leads to a progressive neuronal dysfunction in the chronic stage of the injury. This dysfunction is characterized by premature exhaustion of muscle activity during assisted locomotion, which is associated with the emergence of abnormal reflex responses. Here, we hypothesize that undirected compensatory plasticity within neural systems caudal to a severe spinal cord injury contributes to the development of neuronal dysfunction in the chronic stage of the injury. We evaluated alterations in functional, electrophysiological and neuromorphological properties of lumbosacral circuitries in adult rats with a staggered thoracic hemisection injury. In the chronic stage of the injury, rats exhibited significant neuronal dysfunction, which was characterized by co-activation of antagonistic muscles, exhaustion of locomotor muscle activity, and deterioration of electrochemically-enabled gait patterns. As observed in humans, neuronal dysfunction was associated with the emergence of abnormal, long-latency reflex responses in leg muscles. Analyses of circuit, fibre and synapse density in segments caudal to the spinal cord injury revealed an extensive, lamina-specific remodelling of neuronal networks in response to the interruption of supraspinal input. These plastic changes restored a near-normal level of synaptic input within denervated spinal segments in the chronic stage of injury. Syndromic analysis uncovered significant correlations between the development of neuronal dysfunction, emergence of abnormal reflexes, and anatomical remodelling of lumbosacral circuitries. Together, these results suggest that spinal neurons deprived of supraspinal input strive to re-establish their synaptic environment. However, this undirected compensatory plasticity forms aberrant neuronal circuits, which may engage inappropriate combinations of sensorimotor networks during gait execution.

Abstract

Severe spinal cord injury in humans leads to a progressive neuronal dysfunction in the chronic stage of the injury. This dysfunction is characterized by premature exhaustion of muscle activity during assisted locomotion, which is associated with the emergence of abnormal reflex responses. Here, we hypothesize that undirected compensatory plasticity within neural systems caudal to a severe spinal cord injury contributes to the development of neuronal dysfunction in the chronic stage of the injury. We evaluated alterations in functional, electrophysiological and neuromorphological properties of lumbosacral circuitries in adult rats with a staggered thoracic hemisection injury. In the chronic stage of the injury, rats exhibited significant neuronal dysfunction, which was characterized by co-activation of antagonistic muscles, exhaustion of locomotor muscle activity, and deterioration of electrochemically-enabled gait patterns. As observed in humans, neuronal dysfunction was associated with the emergence of abnormal, long-latency reflex responses in leg muscles. Analyses of circuit, fibre and synapse density in segments caudal to the spinal cord injury revealed an extensive, lamina-specific remodelling of neuronal networks in response to the interruption of supraspinal input. These plastic changes restored a near-normal level of synaptic input within denervated spinal segments in the chronic stage of injury. Syndromic analysis uncovered significant correlations between the development of neuronal dysfunction, emergence of abnormal reflexes, and anatomical remodelling of lumbosacral circuitries. Together, these results suggest that spinal neurons deprived of supraspinal input strive to re-establish their synaptic environment. However, this undirected compensatory plasticity forms aberrant neuronal circuits, which may engage inappropriate combinations of sensorimotor networks during gait execution.

Statistics

Citations

Dimensions.ai Metrics
34 citations in Web of Science®
41 citations in Scopus®
56 citations in Microsoft Academic
Google Scholar™

Altmetrics

Downloads

5 downloads since deposited on 31 Jan 2014
5 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Balgrist University Hospital, Swiss Spinal Cord Injury Center
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:November 2013
Deposited On:31 Jan 2014 09:28
Last Modified:03 Aug 2018 15:18
Publisher:Oxford University Press
ISSN:0006-8950
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/brain/awt204
PubMed ID:24080153

Download

Download PDF  'Undirected compensatory plasticity contributes to neuronal dysfunction after severe spinal cord injury'.
Preview
Content: Published Version
Language: English
Filetype: PDF (Nationallizenz 142-005)
Size: 2MB
View at publisher