ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Calcineurin signaling mediates activity-dependent relocation of the axon initial segment.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 129 citations in OpenAlex.
- Axon Initial Segment: Structure, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Robust activity-dependent mitochondrial calcium dynamics at the AIS is dispensable for action potential generation.The Journal of physiology · 2026Article
- A distinct PP2A subunit regulates local protein phosphorylation at the axon initial segment.Nature communications · 2025Article
- Axon initial segment structure and function in health and disease.Physiological reviews · 2025Review
- Visual activity enhances neuronal excitability in thalamic relay neurons.Science advances · 2025Article
- Unveiling the cell biology of hippocampal neurons with dendritic axon origin.The Journal of cell biology · 2025Article
- Modulation of axon excitable domains by astrocytes and microglia.Frontiers in cellular neuroscience · 2025Review
- Static magnetic stimulation induces structural plasticity at the axon initial segment of inhibitory cortical neurons.Scientific reports · 2024Article
- Actin polymerization and longitudinal actin fibers in axon initial segment plasticity.Frontiers in molecular neuroscience · 2024Article
- Concussive Head Trauma Deranges Axon Initial Segment Function in Axotomized and Intact Layer 5 Pyramidal Neurons.Journal of neurotrauma · 2024Article
- Sodium channel endocytosis drives axon initial segment plasticity.Science advances · 2023Article
- Axon Initial Segment GABA Inhibits Action Potential Generation throughout Periadolescent Development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- The Amyloid Precursor Protein Modulates the Position and Length of the Axon Initial Segment.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- CDK5/p35-Dependent Microtubule Reorganization Contributes to Homeostatic Shortening of the Axon Initial Segment.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Structural plasticity of the axon initial segment in rat hippocampal granule cells following high frequency stimulation and LTP induction.Frontiers in neuroanatomy · 2023Article
- Tracking axon initial segment plasticity using high-density microelectrode arrays: A computational study.Frontiers in neuroinformatics · 2022Article
- Regulation of Axon Initial Segment Diameter by COUP-TFI Fine-tunes Action Potential Generation.Neuroscience bulletin · 2022Article
- Review
- Alterations of the axon initial segment in multiple sclerosis grey matter.Brain communications · 2022Article
- Tau reduction affects excitatory and inhibitory neurons differently, reduces excitation/inhibition ratios, and counteracts network hypersynchrony.Cell reports · 2021Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The axon initial segment (AIS) is a specialized neuronal subcompartment located at the beginning of the axon that is crucially involved in both the generation of action potentials and the regulation of neuronal polarity. We recently showed that prolonged neuronal depolarization produces a distal shift of the entire AIS structure away from the cell body, a change associated with a decrease in neuronal excitability. Here, we used dissociated rat hippocampal cultures, with a major focus on the dentate granule cell (DGC) population, to explore the signaling pathways underlying activity-dependent relocation of the AIS. First, a pharmacological screen of voltage-gated calcium channels (VGCCs) showed that AIS relocation is triggered by activation of L-type Cav1 VGCCs with negligible contribution from any other VGCC subtypes. Additional pharmacological analysis revealed that downstream signaling events are mediated by the calcium-sensitive phosphatase calcineurin; inhibition of calcineurin with either FK506 or cyclosporin A totally abolished both depolarization- and optogenetically-induced activity-dependent AIS relocation. Furthermore, calcineurin activation is sufficient for AIS plasticity, because expression of a constitutively active form of the phosphatase resulted in relocation of the AIS of DGCs without a depolarizing stimulus. Finally, we assessed the role of calcineurin in other forms of depolarization-induced plasticity. Neither membrane resistance changes nor spine density changes were affected by FK506 treatment, suggesting that calcineurin acts via a separate pathway to modulate AIS plasticity. Together, these results emphasize calcineurin as a vital player in the regulation of intrinsic plasticity as governed by the AIS.
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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.