Durand Jacques, Filipchuk Anton
Institut de Neurosciences de la Timone (INT) P3M team, Aix Marseille Université, Marseille, cedex 05, France.
Department for Integrative and Computational Neuroscience (ICN), Paris-Saclay Institute of Neuroscience (NeuroPSI), Gif-sur-Yvette, France.
Adv Neurobiol. 2022;28:353-373. doi: 10.1007/978-3-031-07167-6_14.
In this chapter, we review electrical and morphological properties of lumbar motoneurons during postnatal development in wild-type (WT) and transgenic superoxide dismutase 1 (SOD1) mice, models of amyotrophic lateral sclerosis. First we showed that sensorimotor reflexes do not develop normally in transgenic SOD1 pups. Fictive locomotor activity recorded in in vitro whole brainstem/spinal cord preparations was not induced in these transgenic SOD1 mice using NMDA and 5HT in contrast to WT mice. Further, abnormal electrical properties were detected as early as the second postnatal week in lumbar motoneurons of SOD1 mice while they develop clinical symptoms several months after birth. We compared two different strains of mice (G85R and G93A) at the same postnatal period using intracellular recordings and patch clamp recordings of WT and SOD1 motoneurons. We defined three types of motoneurons according to their discharge firing pattern (transient, sustained and delayed onset firing) when motor units are not yet mature. The delayed-onset firing motoneurons had the higher rheobase compared to the transient and sustained firing groups in the WT mice. We demonstrated hypoexcitability in the delayed onset-firing motoneurons of SOD1 mice. Intracellular staining of motoneurons revealed dendritic overbranching in SOD1 lumbar motoneurons that was more pronounced in the sustained firing motoneurons. We suggested that motoneuronal hypoexcitability is an early pathological sign affecting a subset of lumbar motoneurons in the spinal cord of SOD1 mice.
在本章中，我们回顾了野生型（WT）和转基因超氧化物歧化酶1（SOD1）小鼠（肌萎缩侧索硬化症模型）出生后发育过程中腰段运动神经元的电学和形态学特性。首先，我们发现转基因SOD1幼崽的感觉运动反射发育不正常。与野生型小鼠相比，在体外全脑干/脊髓制剂中记录到的模拟运动活动在这些转基因SOD1小鼠中不能通过使用NMDA和5HT诱导产生。此外，早在出生后第二周就在SOD1小鼠的腰段运动神经元中检测到异常电学特性，而它们在出生后几个月才出现临床症状。我们在同一出生后时期使用细胞内记录和膜片钳记录对野生型和SOD1运动神经元的两种不同品系小鼠（G85R和G93A）进行了比较。当运动单位尚未成熟时，我们根据其放电模式（瞬态、持续和延迟起始放电）定义了三种类型的运动神经元。在野生型小鼠中，延迟起始放电的运动神经元与瞬态和持续放电组相比具有更高的阈强度。我们证明了SOD1小鼠延迟起始放电的运动神经元兴奋性降低。运动神经元的细胞内染色显示SOD1腰段运动神经元存在树突过度分支，在持续放电的运动神经元中更为明显。我们认为运动神经元兴奋性降低是影响SOD1小鼠脊髓中一部分腰段运动神经元的早期病理标志。
