Khalki Loubna, Sadlaoud Karina, Lerond Julie, Coq Jacques-Olivier, Brezun Jean-Michel, Vinay Laurent, Coulon Patrice, Bras Hélène
Institut de Neurosciences de la Timone, UMR 7289, Team P3M, CNRS and Aix Marseille Université, Marseille, France; Neuroscience Laboratory, Faculty of Medicine, Mohammed VI University of Health Sciences, Casablanca, Morocco.
Institut de Neurosciences de la Timone, UMR 7289, Team P3M, CNRS and Aix Marseille Université, Marseille, France.
Exp Neurol. 2018 Jan;299(Pt A):1-14. doi: 10.1016/j.expneurol.2017.09.002. Epub 2017 Sep 14.
Rats with complete spinal cord transection (SCT) can recover hindlimb locomotor function under strategies combining exercise training and 5-HT agonist treatment. This recovery is expected to result from structural and functional re-organization within the spinal cord below the lesion. To begin to understand the nature of this reorganization, we examined synaptic changes to identified gastrocnemius (GS) or tibialis anterior (TA) motoneurons (MNs) in SCT rats after a schedule of early exercise training and delayed 5-HT agonist treatment. In addition, we analyzed changes in distribution and number of lumbar interneurons (INs) presynaptic to GS MNs using retrograde transneuronal transport of rabies virus. In SCT-untrained rats, we found few changes in the density and size of inhibitory and excitatory inputs impinging on cell bodies of TA and GS MNs compared to intact rats, whereas there was a marked trend for a reduction in the number of premotor INs connected to GS MNs. In contrast, after training of SCT rats, a significant increase of the density of GABAergic and glycinergic axon terminals was observed on both GS and TA motoneuronal cell bodies, as well as of presynaptic P-boutons on VGLUT1 afferents. Despite these changes in innervation the number of premotor INs connected to GS MNs was similar to control values although some new connections to MNs were observed. These results suggest that adaptation of gait patterns in SCT-trained rats was accompanied by changes in the innervation of lumbar MNs while the distribution of the spinal premotor circuitry was relatively preserved.
完全性脊髓横断(SCT)大鼠在运动训练和5-羟色胺(5-HT)激动剂治疗相结合的策略下可恢复后肢运动功能。这种恢复预期源于损伤平面以下脊髓内的结构和功能重组。为了开始理解这种重组的本质,我们在早期运动训练和延迟5-HT激动剂治疗方案后,检查了SCT大鼠中已识别的腓肠肌(GS)或胫前肌(TA)运动神经元(MNs)的突触变化。此外,我们使用狂犬病病毒逆行跨神经元运输分析了GS运动神经元突触前腰段中间神经元(INs)的分布和数量变化。在未经训练的SCT大鼠中,与完整大鼠相比,我们发现作用于TA和GS运动神经元胞体的抑制性和兴奋性输入的密度和大小几乎没有变化,而与GS运动神经元相连的运动前中间神经元数量有明显减少的趋势。相比之下,在对SCT大鼠进行训练后,在GS和TA运动神经元胞体上观察到GABA能和甘氨酸能轴突终末的密度显著增加,以及VGLUT1传入纤维上突触前P小体的密度显著增加。尽管神经支配有这些变化,但与GS运动神经元相连的运动前中间神经元数量与对照值相似,尽管观察到一些与运动神经元的新连接。这些结果表明,SCT训练大鼠步态模式的适应性伴随着腰段运动神经元神经支配的变化,而脊髓运动前电路的分布相对保持不变。