ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Myelin loss and axonal ion channel adaptations associated with gray matter neuronal hyperexcitability.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- Persistent sodium currents in neurons: potential mechanisms and pharmacological blockers.Pflugers Archiv : European journal of physiology · 2024Pooled it
- Article
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- Junctions in Jeopardy: the neuromuscular junction is a selective pathological target in Charcot-Marie-Tooth disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Metabolic Symbiosis and Vulnerability in the CNS Axon-Myelin Unit.Cellular and molecular neurobiology · 2026Review
- Endoplasmic Reticulum Stress Mediates Axon Initial Segment Shortening: Implications for Diabetic Brain Complications.Journal of molecular neuroscience : MN · 2025Article
- Layer 5 myelination gates corticothalamic coincidence detection.Nature communications · 2025Article
- Axon collateralization and focal myelin dystrophy alter action potential propagation in multicompartment pyramidal neuron models.PLoS computational biology · 2025Article
- Oligodendrocytes support functional development of subcortical premotor neurons and navigation.bioRxiv : the preprint server for biology · 2025Article
- Transient juvenile demyelination impairs maturation and function of parvalbumin-positive interneurons in the prefrontal cortex.PLoS biology · 2025Article
- A focus on the normal-appearing white and gray matter within the multiple sclerosis brain: a link to smoldering progression.Acta neuropathologica · 2025Review
- Scn2a-linked myelination deficits and synaptic plasticity alterations drive auditory processing disorders in an ASD mouse model.Nature communications · 2025Article
- Hypomyelination in autism-associated neuroligin-3 mutant mice impairs parvalbumin interneuron excitability, gamma oscillations, and sensory discrimination.Nature communications · 2025Article
- White Matter, Cognition, and Electrophysiological Variables in Bipolar Disorder: Using Multimodal Integration of Biomarker Variables Associated With Bipolar Disorder to Elucidate Deficits.Bipolar disorders · 2025Article
- Investigation of the Neurotoxicity Mechanisms of NiInternational journal of molecular sciences · 2025Article
- Astroglial modulation of synaptic function in the non-demyelinated cerebellar cortex is dependent on MyD88 signaling in a model of toxic demyelination.Journal of neuroinflammation · 2025Article
- Hyperventilation-Induced Nystagmus in Acute Unilateral Vestibulopathy: A Correlation with Vestibulo-ocular Reflex Gain and Clinical Implication.The journal of international advanced otology · 2024Article
- CD8+ T cells recognizing a neuron-restricted antigen injure axons in a model of multiple sclerosis.The Journal of clinical investigation · 2023Article
- A class-specific effect of dysmyelination on the excitability of hippocampal interneurons.eLife · 2023Article
- Neuron-oligodendrocyte potassium shuttling at nodes of Ranvier protects against inflammatory demyelination.The Journal of clinical investigation · 2023Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Myelination and voltage-gated ion channel clustering at the nodes of Ranvier are essential for the rapid saltatory conduction of action potentials. Whether myelination influences the structural organization of the axon initial segment (AIS) and action potential initiation is poorly understood. Using the cuprizone mouse model, we combined electrophysiological recordings with immunofluorescence of the voltage-gated Nav1.6 and Kv7.3 subunits and anchoring proteins to analyze the functional and structural properties of single demyelinated neocortical L5 axons. Whole-cell recordings demonstrated that neurons with demyelinated axons were intrinsically more excitable, characterized by increased spontaneous suprathreshold depolarizations as well as antidromically propagating action potentials ectopically generated in distal parts of the axon. Immunofluorescence examination of demyelinated axons showed that βIV-spectrin, Nav1.6, and the Kv7.3 channels in nodes of Ranvier either dissolved or extended into the paranodal domains. In contrast, while the AIS in demyelinated axons started more closely to the soma, ankyrin G, βIV-spectrin, and the ion channel expression were maintained. Structure-function analysis and computational modeling, constrained by the AIS location and realistic dendritic and axonal morphologies, confirmed that a more proximal onset of the AIS slightly reduced the efficacy of action potential generation, suggesting a compensatory role. These results suggest that oligodendroglial myelination is not only important for maximizing conduction velocity, but also for limiting hyperexcitability of pyramidal neurons.
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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.