In amyotrophic lateral sclerosis (ALS), large motoneurons degenerate first, causing muscle weakness. Transgenic mouse models with a mutation in the gene encoding the enzyme superoxide dismutase 1 (SOD1) revealed that motoneurons innervating the fast-fatigable muscular fibres disconnect very early. The cause of this peripheric disconnection has not yet been established. Early pathological signs were described in motoneurons during the postnatal period of SOD1 transgenic mice. Here, we investigated whether the early changes of electrical and morphological properties previously reported in the SOD1^G85R strain also occur in the SOD1^G93A-low expressor line with particular attention to the different subsets of motoneurons defined by their discharge firing pattern (transient, sustained, or delayed-onset firing). Intracellular staining and recording were performed in lumbar motoneurons from entire brainstem-spinal cord preparations of SOD1^G93A-low transgenic mice and their WT littermates during the second postnatal week. Our results show that SOD1^G93A-low motoneurons exhibit a dendritic overbranching similar to that described previously in the SOD1^G85R strain at the same age. Further we found an hypoexcitability in the delayed-onset firing SOD1^G93A-low motoneurons (lower gain and higher voltage threshold). We conclude that dendritic overbranching and early hypoexcitability are common features of both low expressor SOD1 mutants (G85R and G93A-low). In the high-expressor SOD1^G93A line, we found hyperexcitability in the sustained firing motoneurons at the same period, suggesting a delay in compensatory mechanisms. Overall, our results suggest that the hypoexcitability indicate an early dysfunction of the delayed-onset motoneurons and could account as early pathological signs of the disease.

在肌萎缩性侧索硬化症（ALS）中，大型运动神经元首先退化，导致肌肉无力。具有编码超氧化物歧化酶1（SOD1）的基因突变的转基因小鼠模型显示，支配快速易降解的肌纤维的运动神经元很早就断开连接。尚未确定这种外围连接断开的原因。在SOD1转基因小鼠出生后的运动神经元中描述了早期病理征象。在这里，我们调查了先前在SOD1 ^G85R菌株中报道的电学和形态学特性的早期变化是否也发生在SOD1 ^G93A-low中在表达方面，运动神经元的不同子集由放电放电模式（瞬态，持续或延迟发作）定义。在产后第二周，对来自SOD1 ^G93A低转基因小鼠的整个脑干-脊髓组织的WT运动同窝^仔的腰运动神经元进行细胞内染色和记录。我们的结果表明，SOD1 G93A-^低运动神经元显示出树突状超支，类似于先前在相同年龄的SOD1 ^G85R株中所述。此外，我们在延迟发作的SOD1 ^G93A-low中发现了兴奋^不足运动神经元（较低的增益和较高的电压阈值）。我们得出结论，树突过度分支和早期低兴奋性是两个低表达SOD1突变体（G85R和G93A-low）的共同特征。在高表达SOD1 ^G93A细胞系中，我们发现持续激发的运动神经元在同一时期表现出超兴奋性，这提示了补偿机制的延迟。总的来说，我们的结果表明，低兴奋性表明延迟发作的运动神经元的早期功能异常，并且可以解释为该疾病的早期病理征象。