Plasticity of motor network and function in the absence of corticospinal projection

Abstract

Despite the obvious clinical interest, our understanding of how developmental mechanisms are redeployed during degeneration and regeneration after brain and spinal cord injuries remains quite rudimentary. In animal models of spinal cord injury, although spontaneous regeneration of descending axons is limited, compensation by intact corticospinal axons, descending tracts from the brainstem, and local intrinsic spinal networks all contribute to the recovery of motor function. Here, we investigated spontaneous motor compensation and plasticity that occur in the absence of corticospinal tract, using Celsr3|Emx1 mice in which the corticospinal tract is completely and specifically absent as a consequence of Celsr3 inactivation in the cortex. Mutant mice had no paresis, but displayed hyperactivity in open-field, and a reduction in skilled movements in food pellet manipulation tests. The number of spinal motoneurons was reduced and their terminal arbors at neuromuscular junctions were atrophic, which was reflected in electromyography deficits. Rubrospinal projections, calretinin-positive propriospinal projections, afferent innervation of motoneurons by calretinin-positive segmental interneurons, and terminal ramifications of monoaminergic projections were significantly increased. Contrary to control animals, mutants also developed a severe and persistent disability of forelimb use following the section of the rubrospinal tract at the C4 spinal level. These observations demonstrate for the first time that the congenital absence of the corticospinal tract induces spontaneous plasticity, both at the level of the motor spinal cord and in descending monoaminergic and rubrospinal projections. Such compensatory mechanisms could be recruited in case of brain or spinal cord lesion or degeneration.

EPO-releasing neural precursor cells promote axonal regeneration and recovery of function in spinal cord traumatic injury

“…Serotonin (5-HT) innervation of the cord is involved in the regulation of the central pattern generator and the facilitation of locomotion ( Lemon, 2008 ; Liu et al, 2009 ; Han et al, 2015 ) thus 5-HT immunoreactivity was investigated in the injured cord of untreated or Er-NPCs treated animals. Positive 5-HT staining was detected in the lesion center and in regions 2 mm rostral and caudal to the lesion center ( Fig.…”

Extracellular vimentin is a novel axonal growth facilitator for functional recovery in spinal cord-injured mice

“…Next, spinal cord sections were immunostained for 5-HT to visualize raphespinal tracts in the spinal cord because these tracts are known to predominantly regulate locomotor function192021. Positive 5-HT staining was detected in the lesion center and in regions 2 mm rostral and caudal to the lesion center (Fig.…”

“…Spinal motor neurons terminate in the skeletal muscle in hindlimbs and are regulated by multiple descending tracts, propriospinal neurons and interneurons2021. The serotonergic raphespinal tract is one of the main descending tracts that regulate voluntary movement222324.…”

A Comparative Study of Three Interneuron Types in the Rat Spinal Cord

“…This suggested that Cr interneurons might be involved in posture and movement regulation. The study of Celsr3|Emx1 mice model showed that Cr neurons in C3-C4 segments were significant increased, which indicated contributing to remodeling of spinal motor circuits [ 43 ]. Both others’ and our present data showed that Calb interneurons were located obviously in the superfical dorsal horn and layer IX of rat and mouse spinal cords [ 13 , 32 , 35 ].…”