Résumé :
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Mechanisms underlying muscle spasticity: alterations of the neural network and inhibitory synaptic transmission after spinal cord injuryKarina Sadlaoud, Pascale Boulenguez, Patrice Coulon, Laurent Vinay and Hne BrasLaboratoire Plasticitysio-Pathologie de la motricitasticity is a disorder associated with muscular hypertonicity and pain, which occurs in association with spinal cord injury (SCI) and multiple sclerosis or metabolic diseases. We will focus on plasticity of inhibitory synaptic transmission, which appears to be decreased in several pathologies of the nervous system, including SCI. Adult rats with thoracic spinal cord transection (SCT) are used as model of spasticity. The occurrence of spasticity is tested by monitoring the rate-dependent depression of the H reflex (RDD) 3 weeks and 4 months after SCT. Concomitantly the alterations of the reciprocal inhibition between antagonistic muscles (ankle flexor tibialis (Tib) versus ankle extensor gastrocnemius (GS)) are measured in vivo. Three weeks after SCT, a significant decrease of the reciprocal inhibition is observed. Four months after SCI, the reciprocal inhibition is suppressed and switched to reciprocal facilitation in some cases. This deterioration may explain the co-contraction of antagonist muscles observed in spastic patients. The suppression of the reciprocal inhibition can be due to an alteration of network of inhibitory interneurones projecting to motoneurons and/or to modifications of membrane properties of the motoneurons (MNs).To test these hypotheses the membrane expression of GABAA and Glycine receptors (GABAAR and GlyRalpha1) was studied by immunohistochemistry in in Tib and GS MNs retrogradely identified with retrograde dyes. One month after SCT, the expression of GlyR did not significantly change in Tib Mns, while a significant upregulation of GABAAR was observed. In GS Mns, a significant upregulation of both GlyR and GABAAR occurred. This state was transitory since a global significant decrease of expression of GlyR and GABAAR was observed in both pools of MNs 4 months after SCI. The upregulation of the expression of GABAAR observed 1 month after SCI, which seems inconsistent with the decrease of the reciprocal inhibition measured at this time, can be considered as a post-reactionnal compensatory mechanism of the inhibitory synaptic transmission to lumbar Mns, in response to the suppression of the descending pathways.Changes in the inhibitory premotor networks were mapped by use of Rabies Virus as a transynaptic retrograde tracer. These tracing experiments enabled to compare the groups of last order interneurons (loINs) connected to pools of Mns innervating antagonist muscles (Tib versus GS). The preliminary results suggest a transversal reorganization of the premotor network after SCI.
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