Institut de Neurosciences de la Timone, UMR 7289, CNRS and Aix Marseille Université, Campus Santé Timone, 13385, Marseille, France.
Institut de Neurosciences de la Timone, UMR 7289, CNRS and Aix Marseille Université, Campus Santé Timone, 13385, Marseille, France.
J Chem Neuroanat. 2021 Apr;113:101847. doi: 10.1016/j.jchemneu.2020.101847. Epub 2020 Jul 9.
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.
这篇综述评估了完全性脊髓横断(SCT)对亚损伤性腰运动神经元(MNs)抑制性突触传递可塑性的影响,区分了新生和成年大鼠的研究。在新生 SCT 后,观察到甘氨酸受体的正常成熟上调。另一方面,GABAA 受体的发育性下调以及共转运体 KCC2 的上调被阻止,但 NKCC1 的正常减少未被阻止。在成年 SCT 大鼠中,2 个月损伤后,控制脊髓 MNs 抑制的主要贡献者——甘氨酸能突触传递具有正常的控制水平。另一方面,通过前信号水平的上调和突触后受体密度的下调改变了 GABA 能传递。在所有测试的损伤后时间(24 小时至 4 个月),KCC2 膜表达均下调,从而使 Cl-平衡电位去极化并降低突触后抑制的强度。甘氨酸能前和后信号的保留可能是成年 SCT 大鼠运动康复计划成功的关键因素。然而,这些数据突出表明,需要制定策略来恢复腰 MNs 中的 KCC2 水平,以稳定兴奋/抑制平衡,这对于有效控制骨骼肌活动至关重要。