ArticleThe Journal of physiology2014
Adult spinal motoneurones are not hyperexcitable in a mouse model of inherited amyotrophic lateral sclerosis.
Article in The Journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 3 of them syntheses that pooled it.
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Who cites it
88 citing papers in PubMed, 3 syntheses or guidelines pooled it, 145 citations in OpenAlex.
- Elucidating the Role of Cerebellar Synaptic Dysfunction in C9orf72-ALS/FTD - a Systematic Review and Meta-Analysis.Cerebellum (London, England) · 2022Pooled it
- Meta-analysis of biological variables' impact on spinal motoneuron electrophysiology data.Journal of neurophysiology · 2020Pooled it
- State of the field: An informatics-based systematic review of the SOD1-G93A amyotrophic lateral sclerosis transgenic mouse model.Amyotrophic lateral sclerosis & frontotemporal degeneration · 2015Pooled it
- Chronic Diazepam Reveals Excessive Homeostatic Gain in SOD1International journal of molecular sciences · 2026Article
- Chronic diazepam reveals excessive homeostatic gain in SOD1bioRxiv : the preprint server for biology · 2026Article
- Spinal motoneuron excitability is homeostatically regulated through β-adrenergic neuromodulation in wild-type and presymptomatic SOD1 mice.Progress in neurobiology · 2026Article
- SK channel upregulation and sex-specific mechanisms drive spinal motoneuron reduced excitability with age.Frontiers in aging neuroscience · 2026Article
- Increase in Ia Afferent Synaptic Excitation of SOD1 G93A Mouse Motoneurons by 2-Week Anodal Trans-Spinal Direct Current Stimulation Does Not Ameliorate the Cellular Burden of the Disease.The European journal of neuroscience · 2025Article
- Embryonic motor neuron programming factors reactivate immature gene expression and suppress ALS pathologies in postnatal motor neurons.Nature neuroscience · 2025Article
- Synaptic imbalance and increased inhibition impair motor function in SMA.Science advances · 2025Article
- Trimetazidine stimulates intracellular CaScientific reports · 2025Article
- A Multi-Scale, High-Fidelity Computational Model of the Mouse Triceps Surae Motor Pool.Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference · 2025Article
- TDP-43 pathology is sufficient to drive axon initial segment plasticity and hyperexcitability of spinal motoneurones in vivo in the TDP43-ΔNLS model of Amyotrophic Lateral Sclerosis.Acta neuropathologica communications · 2025Article
- Spinal microcircuits go through multiphasic homeostatic compensations in a mouse model of motoneuron degeneration.Cell reports · 2024Article
- Spinal microcircuits go through multiphasic homeostatic compensations in a mouse model of motoneuron degeneration.bioRxiv : the preprint server for biology · 2024Article
- Dysregulation of persistent inward and outward currents in spinal motoneurons of symptomatic SOD1-G93A mice.The Journal of physiology · 2024Article
- Revisiting distinct nerve excitability patterns in patients with amyotrophic lateral sclerosis.Brain : a journal of neurology · 2024Article
- How do we get from hyperexcitability to excitotoxicity in amyotrophic lateral sclerosis?Brain : a journal of neurology · 2024Review
- Homozygous ALS-linked mutations in TARDBP/TDP-43 lead to hypoactivity and synaptic abnormalities in human iPSC-derived motor neurons.iScience · 2024Article
- Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
In amyotrophic lateral sclerosis (ALS), an adult onset disease in which there is progressive degeneration of motoneurones, it has been suggested that an intrinsic hyperexcitability of motoneurones (i.e. an increase in their firing rates), contributes to excitotoxicity and to disease onset. Here we show that there is no such intrinsic hyperexcitability in spinal motoneurones. Our studies were carried out in an adult mouse model of ALS with a mutated form of superoxide dismutase 1 around the time of the first muscle fibre denervations. We showed that the recruitment current, the voltage threshold for spiking and the frequency-intensity gain in the primary range are all unchanged in most spinal motoneurones, despite an increased input conductance. On its own, increased input conductance would decrease excitability, but the homeostasis for excitability is maintained due to an upregulation of a depolarizing current that is activated just below the spiking threshold. However, this homeostasis failed in a substantial fraction of motoneurones, which became hypoexcitable and unable to produce sustained firing in response to ramps of current. We found similar results both in lumbar motoneurones recorded in anaesthetized mice, and in sacrocaudal motoneurones recorded in vitro, indicating that the lack of hyperexcitability is not caused by anaesthetics. Our results suggest that, if excitotoxicity is indeed a mechanism leading to degeneration in ALS, it is not caused by the intrinsic electrical properties of motoneurones but by extrinsic factors such as excessive synaptic excitation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.