Amyotrophic lateral sclerosis is a neurodegenerative disease preferentially affecting motoneurones. Transgenic mouse models have been used to investigate the role of abnormal motoneurone excitability in this disease. Whilst an increased excitability has repeatedly been demonstrated in vitro in neonatal and embryonic preparations from SOD1 mouse models, the results from the only studies to record in vivo from spinal motoneurones in adult SOD1 models have produced conflicting findings. Deficits in repetitive firing have been reported in G93A SOD1 ^{(high copy number)} mice but not in presymptomatic G127X SOD1 mice despite shorter motoneurone axon initial segments (AISs) in these mice. These discrepancies may be due to the earlier disease onset and prolonged disease progression in G93A SOD1 mice with recordings potentially performed at a later sub-clinical stage of the disease in this mouse. To test this, and to explore how the evolution of excitability changes with symptom onset we performed in vivo intracellular recording and AIS labelling in G127X SOD1 mice immediately after symptom onset. No reductions in repetitive firing were observed showing that this is not a common feature across all ALS models. Immunohistochemistry for the Na⁺ channel Nav1.6 showed that motoneurone AISs increase in length in G127X SOD1 mice at symptom onset. Consistent with this, the rate of rise of AIS components of antidromic action potentials were significantly faster confirming that this increase in length represents an increase in AIS Na⁺ channels occurring at symptom onset in this model.

肌萎缩性侧索硬化症是一种神经退行性疾病，会优先影响运动神经元。转基因小鼠模型已用于研究异常的运动神经元兴奋性在这种疾病中的作用。虽然增加的兴奋性曾多次被证明在体外从SOD1小鼠模型新生儿和胚胎制剂，从只研究的结果，记录在体内在成年SOD1模型脊髓运动神经元已经产生冲突的发现。据报道，G93A SOD1 ^{（高拷贝数）}存在重复发射的缺陷小鼠，但没有症状前G127X SOD1小鼠，尽管这些小鼠中的运动神经元轴突起始节段（AIS）较短。这些差异可能是由于在G93A SOD1小鼠中较早的疾病发作和较长的疾病进展，而在该小鼠的疾病的亚临床阶段可能会进行记录。为了对此进行测试，并探讨兴奋性的演变如何随症状发作而变化，我们在症状发作后立即对G127X SOD1小鼠进行了体内细胞内记录和AIS标记。没有观察到重复射击的减少，这表明这不是所有ALS模型的共同特征。Na ^+的免疫组织化学Nav1.6通道显示，症状发作时G127X SOD1小鼠的运动神经元AIS长度增加。与此相一致，ADS组分的抗肢体动作电位的上升速度明显更快，这证实了这种长度的增加代表了该模型在症状发作时出现的AIS Na ⁺通道的增加。