Research output: Contribution to journal › Article › peer-review
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.
In: Brain; a journal of neurology, Vol. 136, No. 11, 11.2013, p. 3347-3361.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Undirected compensatory plasticity contributes to neuronal dysfunction after severe spinal cord injury
AU - Beauparlant, Janine
AU - Van Den Brand, Rubia
AU - Barraud, Quentin
AU - Friedli, Lucia
AU - Musienko, Pavel
AU - Dietz, Volker
AU - Courtine, Grégoire
PY - 2013/11
Y1 - 2013/11
N2 - 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, longlatency 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.
AB - 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, longlatency 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.
KW - Compensatory plasticity
KW - Exhaustion of locomotor activity
KW - Neuronal dysfunction
KW - Spinal cord injury
KW - Syndromic analysis
UR - http://www.scopus.com/inward/record.url?scp=84890481117&partnerID=8YFLogxK
U2 - 10.1093/brain/awt204
DO - 10.1093/brain/awt204
M3 - Article
C2 - 24080153
VL - 136
SP - 3347
EP - 3361
JO - Brain
JF - Brain
SN - 0006-8950
IS - 11
ER -
ID: 5835886