ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Pacemaker rate and depolarization block in nigral dopamine neurons: a somatic sodium channel balancing act.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 65 citations in OpenAlex.
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- Complex excitability and "flipping" of granule cells: An experimental and computational study.PloS one · 2026Article
- A hardwired neural circuit for temporal difference learning.bioRxiv : the preprint server for biology · 2025Article
- Corticonigral projections recruit substantia nigra pars lateralis dopaminergic neurons for auditory threat memories.Nature communications · 2025Article
- Depolarization block induction via slow NaScientific reports · 2025Article
- PKC-dependent enhancement of glutamate input to VTA dopamine neurons in 3xTg-AD mice.bioRxiv : the preprint server for biology · 2025Article
- Effects of chronic ethanol exposure on dorsal medial striatal neurons receiving convergent inputs from the orbitofrontal cortex and basolateral amygdala.Neuropharmacology · 2025Article
- Functional properties of corticothalamic circuits targeting paraventricular thalamic neurons.Neuron · 2024Article
- Corticonigral projections recruit substantia nigra pars lateralis dopaminergic neurons for auditory threat memories.bioRxiv : the preprint server for biology · 2024Article
- Somatodendritic organization of pacemaker activity in midbrain dopamine neurons.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2024Article
- De novoFrontiers in genetics · 2024Article
- Single-compartment model of a pyramidal neuron, fitted to recordings with current and conductance injection.Biological cybernetics · 2023Article
- Morphological Determinants of Cell-to-Cell Variations in Action Potential Dynamics in Substantia Nigra Dopaminergic Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Intrinsic Morphologic and Physiologic Development of Human Derived Retinal Ganglion Cells In Vitro.Translational vision science & technology · 2021Article
- A new reduced-morphology model for CA1 pyramidal cells and its validation and comparison with other models using HippoUnit.Scientific reports · 2021Article
- Presynaptic vesicular accumulation is required for antipsychotic efficacy in psychotic-like rats.Journal of psychopharmacology (Oxford, England) · 2021Article
- Downregulation of M Current Is Coupled to Membrane Excitability in Sympathetic Neurons Before the Onset of Hypertension.Hypertension (Dallas, Tex. : 1979) · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Midbrain dopamine (DA) neurons are slow intrinsic pacemakers that undergo depolarization (DP) block upon moderate stimulation. Understanding DP block is important because it has been correlated with the clinical efficacy of chronic antipsychotic drug treatment. Here we describe how voltage-gated sodium (Na(V)) channels regulate DP block and pacemaker activity in DA neurons of the substantia nigra using rat brain slices. The distribution, density, and gating of Na(V) currents were manipulated by blocking native channels with tetrodotoxin and by creating virtual channels and anti-channels with dynamic clamp. Although action potentials initiate in the axon initial segment and Na(V) channels are distributed in multiple dendrites, selective reduction of Na(V) channel activity in the soma was sufficient to decrease pacemaker frequency and increase susceptibility to DP block. Conversely, increasing somatic Na(V) current density raised pacemaker frequency and lowered susceptibility to DP block. Finally, when Na(V) currents were restricted to the soma, pacemaker activity occurred at abnormally high rates due to excessive local subthreshold Na(V) current. Together with computational simulations, these data show that both the slow pacemaker rate and the sensitivity to DP block that characterizes DA neurons result from the low density of somatic Na(V) channels. More generally, we conclude that the somatodendritic distribution of Na(V) channels is a major determinant of repetitive spiking frequency.
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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.