Spinal motoneurones are intrinsically more responsive in the adult G93A SOD1 mouse model of amyotrophic lateral sclerosis
| Autor: | Dennis Bo Jensen, Marion Kadlecova, Ilary Allodi, C. F. Meehan |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Adult male Physiology medicine.drug_class animal diseases Transgene SOD1 Mice Transgenic Mice 03 medical and health sciences Superoxide Dismutase-1 0302 clinical medicine In vivo medicine Animals Amyotrophic lateral sclerosis Motor Neurons Superoxide Dismutase business.industry Amyotrophic Lateral Sclerosis nutritional and metabolic diseases medicine.disease In vitro nervous system diseases Disease Models Animal 030104 developmental biology Rheobase Spinal Cord nervous system Barbiturate business Neuroscience 030217 neurology & neurosurgery Intracellular |
| Zdroj: | The Journal of Physiology. 598:4385-4403 |
| ISSN: | 1469-7793 0022-3751 |
| DOI: | 10.1113/jp280097 |
| Popis: | In vitro studies from transgenic Amyotrophic Lateral Sclerosis models have suggested an increased excitability of spinal motoneurones. However, in vivo intracellular recordings from adult ALS mice models have produced conflicting findings. Previous publications using barbiturate anaesthetised G93A SOD1 mice suggested that some motoneurones are hypo-excitable, defined by deficits in repetitive firing. Our own previous recordings in G127X SOD1 mice using different anaesthesia, however, showed no repetitive firing deficits, and increased persistent inward currents at symptom onset. These discrepancies may be due to differences between models, symptomatic stage, anaesthesia or technical differences. To investigate this, we repeated our original experiments, but in adult male G93A mice at both presymptomatic and symptomatic stages, under barbiturate anaesthesia.In vivo intracellular recordings from antidromically identified spinal motoneurones revealed no significant differences in the ability to fire repetitively in the G93A SOD1 mice. Motoneurones in G93A SOD1 mice fired significantly more spontaneous action potentials. Rheobase was significantly lower and the input resistance and input-output gain were significantly higher in both presymptomatic and symptomatic G93A SOD1 mice. This was despite a significant increase in the duration of the post-spike after-hyperpolarisation (AHP) in both presymptomatic and symptomatic G93A SOD1 mice. Finally, evidence of increased activation of persistent inward currents was seen in both presymptomatic and symptomatic G93A SOD1 mice. Our results do not confirm previous reports of hypo-excitability of spinal motoneurones in the G93A SOD1 mouse and demonstrate that the motoneurones do in fact show an increased response to inputs.Key Point SummaryAlthough in vitro recordings using neonatal preparations from mouse models of Amyotrophic Lateral Sclerosis (ALS) suggest increased motoneurone excitability, in vivo recordings in adult ALS mouse models have been conflicting.In adult G93A SOD1 models, spinal motoneurones have previously been shown to have deficits in repetitive firing, in contrast to the G127X SOD1 mouse model.Our in vivo intracellular recordings in barbiturate-anaesthetised adult male G93A SOD1 mice reveal no deficits in repetitive firing either prior to or after symptom onset.We show that deficits in repetitive firing ability can be a consequence of experimental protocol and should not be used alone to classify otherwise normal motoneurones as hypo-excitable.Motoneurones in the G93A SOD1 mice showed an increased response to inputs, with lower rheobase, higher input-output gains and increased activation of persistent inward currents. |
| Databáze: | OpenAIRE |
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