ArticlePLoS computational biology2021
Inactivation mode of sodium channels defines the different maximal firing rates of conventional versus atypical midbrain dopamine neurons.
Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 17 citations in OpenAlex.
- KChIP4a is a Biophysical Amplifier of Inhibition in Atypical Dopamine Neurons and Controls Learning from Negative Prediction Errors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Alzheimer's Pathology Enhances Excitatory Synaptic Input and Integration in VTA Dopamine Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Rebound Bursting Selectively Enables Fast Dynamics in Dopamine Midbrain Neurons Projecting to the Dorsolateral Striatum.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Reduced SK channel control of mesolimbic dopamine neuron firing drives reward seeking adaptations in chronic pain.bioRxiv : the preprint server for biology · 2025Article
- PKC-dependent enhancement of glutamate input to VTA dopamine neurons in 3xTg-AD mice.bioRxiv : the preprint server for biology · 2025Article
- Tau conveys intrinsic hyperactivity of VTA dopamine neurons but an inability to sustain burst firing.bioRxiv : the preprint server for biology · 2025Article
- Ramped kilohertz-frequency signals produce nerve conduction block without onset response.Journal of neural engineering · 2025Article
- Functional properties of corticothalamic circuits targeting paraventricular thalamic neurons.Neuron · 2024Article
- Impact of Unitary Synaptic Inhibition on Spike Timing in Ventral Tegmental Area Dopamine Neurons.eNeuro · 2024Article
- Sodium channel slow inactivation normalizes firing in axons with uneven conductance distributions.Current biology : CB · 2023Article
- Article
- A brief exposure to toluene vapor alters the intrinsic excitability of D2 medium spiny neurons in the rat ventral striatum.Frontiers in neuroscience · 2023Article
- Long-Term Inactivation of Sodium Channels as a Mechanism of Adaptation in CA1 Pyramidal Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
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Abstract
Two subpopulations of midbrain dopamine (DA) neurons are known to have different dynamic firing ranges in vitro that correspond to distinct projection targets: the originally identified conventional DA neurons project to the dorsal striatum and the lateral shell of the nucleus accumbens, whereas an atypical DA population with higher maximum firing frequencies projects to prefrontal regions and other limbic regions including the medial shell of nucleus accumbens. Using a computational model, we show that previously identified differences in biophysical properties do not fully account for the larger dynamic range of the atypical population and predict that the major difference is that originally identified conventional cells have larger occupancy of voltage-gated sodium channels in a long-term inactivated state that recovers slowly; stronger sodium and potassium conductances during action potential firing are also predicted for the conventional compared to the atypical DA population. These differences in sodium channel gating imply that longer intervals between spikes are required in the conventional population for full recovery from long-term inactivation induced by the preceding spike, hence the lower maximum frequency. These same differences can also change the bifurcation structure to account for distinct modes of entry into depolarization block: abrupt versus gradual. The model predicted that in cells that have entered depolarization block, it is much more likely that an additional depolarization can evoke an action potential in conventional DA population. New experiments comparing lateral to medial shell projecting neurons confirmed this model prediction, with implications for differential synaptic integration in the two populations.
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