Differential effects of spinal cord transection on glycinergic and GABAergic synaptic signaling in sub-lesional lumbar motoneurons.

ABSTRACT

This review takes stock on the impact of complete spinal cord transection (SCT) on the plasticity of inhibitory synaptic transmission on sub-lesional lumbar motoneurons (MNs), differentiating between studies in neonate and adult rats. After neonatal SCT, normal maturational up-regulation of glycine receptors was observed. On the other hand, the developmental downregulation of the GABAA receptors, as well as the up-regulation of the co-transporter KCC2 were prevented, but not the normal decrease of NKCC1. In adult SCT rats, glycinergic synaptic transmission, which is the major contributor to spinal MNs inhibition in adulthood, had normal control levels 2 months post-injury. On the other hand, the GABAergic transmission was altered through an up-regulation of the pre-signaling levels and a down-regulation in the density of post synaptic receptors. KCC2 membrane expression was down-regulated at all post-injury times tested (24h to 4 months), thereby depolarizing the Cl- equilibrium potential and reducing the strength of postsynaptic inhibition. The preservation of glycinergic pre- and post signaling is probably a key factor in the success of locomotor rehabilitation programs in adult SCT rats. However, these data highlight the need to develop strategies to restore KCC2 levels in lumbar MNs, to stabilize the excitation/inhibition balance, which is essential to the effective control of skeletal muscle activity.