ArticleNeuroscience2016
Calcium regulation of HCN channels supports persistent activity in a multiscale model of neocortex.
Article in Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
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- Multimodal evidence for a mechanistic model of working memory deficits in schizophrenia.medRxiv : the preprint server for health sciences · 2026Article
- A nullcline-guided discrete-time map for neurons with subcritical Hopf bifurcation dynamics.Frontiers in computational neuroscience · 2026Article
- Computer models predict differential dendritic vulnerability with ischemia and spreading depression.bioRxiv : the preprint server for biology · 2025Article
- rdHSV-CA8 non-opioid analgesic gene therapy decreases somatosensory neuronal excitability by activating Kv7 voltage-gated potassium channels.Frontiers in molecular neuroscience · 2024Article
- Ultrafast simulation of large-scale neocortical microcircuitry with biophysically realistic neurons.eLife · 2022Article
- Excitatory and inhibitory effects of HCN channel modulation on excitability of layer V pyramidal cells.PLoS computational biology · 2022Article
- Insertion of Calcium-Permeable AMPA Receptors during Epileptiform Activity In Vitro Modulates Excitability of Principal Neurons in the Rat Entorhinal Cortex.International journal of molecular sciences · 2021Article
- An uncommon neuronal class conveys visual signals from rods and cones to retinal ganglion cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Mitochondria-associated membranes (MAMs): a potential therapeutic target for treating Alzheimer's disease.Clinical science (London, England : 1979) · 2021Review
- Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels.Frontiers in molecular neuroscience · 2021Review
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- The what, where and how of delay activity.Nature reviews. Neuroscience · 2019Review
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- Dynamics of spontaneous activity in random networks with multiple neuron subtypes and synaptic noise : Spontaneous activity in networks with synaptic noise.Journal of computational neuroscience · 2018Article
- A Simplified Model of Communication Between Time Cells: Accounting for the Linearly Increasing Timing Imprecision.Frontiers in computational neuroscience · 2018Article
- Using NEURON for Reaction-Diffusion Modeling of Extracellular Dynamics.Frontiers in neuroinformatics · 2018Article
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- Multiscale modeling in the clinic: diseases of the brain and nervous system.Brain informatics · 2017Review
- Optimizing computer models of corticospinal neurons to replicate in vitro dynamics.Journal of neurophysiology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Neuronal persistent activity has been primarily assessed in terms of electrical mechanisms, without attention to the complex array of molecular events that also control cell excitability. We developed a multiscale neocortical model proceeding from the molecular to the network level to assess the contributions of calcium (Ca(2+)) regulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in providing additional and complementary support of continuing activation in the network. The network contained 776 compartmental neurons arranged in the cortical layers, connected using synapses containing AMPA/NMDA/GABAA/GABAB receptors. Metabotropic glutamate receptors (mGluR) produced inositol triphosphate (IP3) which caused the release of Ca(2+) from endoplasmic reticulum (ER) stores, with reuptake by sarco/ER Ca(2+)-ATP-ase pumps (SERCA), and influence on HCN channels. Stimulus-induced depolarization led to Ca(2+) influx via NMDA and voltage-gated Ca(2+) channels (VGCCs). After a delay, mGluR activation led to ER Ca(2+) release via IP3 receptors. These factors increased HCN channel conductance and produced firing lasting for ∼1min. The model displayed inter-scale synergies among synaptic weights, excitation/inhibition balance, firing rates, membrane depolarization, Ca(2+) levels, regulation of HCN channels, and induction of persistent activity. The interaction between inhibition and Ca(2+) at the HCN channel nexus determined a limited range of inhibition strengths for which intracellular Ca(2+) could prepare population-specific persistent activity. Interactions between metabotropic and ionotropic inputs to the neuron demonstrated how multiple pathways could contribute in a complementary manner to persistent activity. Such redundancy and complementarity via multiple pathways is a critical feature of biological systems. Mediation of activation at different time scales, and through different pathways, would be expected to protect against disruption, in this case providing stability for persistent activity.
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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.