| | Models | Description |
| 1. |
Ca+/HCN channel-dependent persistent activity in multiscale model of neocortex (Neymotin et al 2016)
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"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 regulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in providing additional and complementary support of continuing activation in the network. ..." |
| 2. |
CA1 pyramidal cell receptor dependent cAMP dynamics (Chay et al. 2016)
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We use a combination of live cell imaging and stochastic modeling of signaling pathways to investigate how noradrenergic receptor stimulation interacts with calcium to control cAMP, required for synaptic plasticity and memory in the hippocampus. Our simulation results explain the mechanism whereby prior noradrenergic receptor stimulation does not enhance the subsequent NMDA stimulated cAMP elevation. Specifically, our results demonstrate the the negative feedback loop from cAMP, through PKA, to PDE4 cannot explain the results, and that switching of the noradrenergic receptor from Gs to Gi is required. |
| 3. |
Calcium waves and mGluR-dependent synaptic plasticity in CA1 pyr. neurons (Ashhad & Narayanan 2013)
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A morphologically realistic, conductance-based model equipped with kinetic schemes that govern several calcium signalling modules and pathways in CA1 pyramidal neurons |
| 4. |
Cell signaling/ion channel variability effects on neuronal response (Anderson, Makadia, et al. 2015)
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" ... We evaluated the impact of molecular variability in the expression of cell signaling components and ion channels
on electrophysiological excitability and neuromodulation. We employed a computational approach that integrated neuropeptide receptor-mediated signaling with electrophysiology. We simulated a population of neurons in which expression levels of a neuropeptide receptor and multiple ion channels were simultaneously
varied within a physiological range. We analyzed the effects of variation on the electrophysiological response to a neuropeptide stimulus. ..." |
| 5. |
Compartmental differences in cAMP signaling pathways in hippocam. CA1 pyr. cells (Luczak et al 2017)
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Model of cAMP signaling pathways in hippocampal CA1 pyramidal neurons investigate mechanisms underlying the experimentally observed difference in cAMP and PKA FRET between proximal and distal dendrites. Simulations show that compartmental difference in PKA activity required enrichment of protein phosphatase in small compartments; neither reduced PKA subunits nor increased PKA substrates were sufficient. |
| 6. |
Endocannabinoid dynamics gate spike-timing dependent depression and potentiation (Cui et al 2016)
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The endocannabinoid (eCB) system is considered involved in synaptic depression.
Recent reports have also linked eCBs to synaptic potentiation. However it is not known how eCB signaling may support such bidirectionality. To question the mechanisms of this phenomena in spike-timing dependent plasticity (STDP) at corticostriatal synapses, we combined electrophysiology experiments with biophysical modeling. We demonstrate that STDP is controlled by eCB levels and dynamics: prolonged and moderate levels of eCB lead to eCB-mediated long-term depression (eCB-tLTD) while short and large eCB transients produce eCB-mediated long-term potentiation (eCB-tLTP). Therefore, just like neurotransmitters glutamate or GABA, eCB form a bidirectional system. |
| 7. |
Multiscale model of olfactory receptor neuron in mouse (Dougherty 2009)
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Collection of XPP (.ode) files simulating the signal transduction (slow) and action potential (fast) currents in the olfactory receptor neuron of mouse. Collection contains model configured for dual odorant pulse delivery and model configured for prolonged odorant delivery. For those interested more in transduction processes, each whole cell recording model comes with a counter part file configured to show just the slow transduction current for ease of use and convenience. These transduction-only models typically run faster than the full multi-scale models but do not demonstrate action potentials. |
| 8. |
Pancreatic Beta Cell signalling pathways (Fridlyand & Philipson 2016) (MATLAB)
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This is a 3rd party implementation of Fridlyand & Philipson 2016 who's abstract begins "Insulin secretory in pancreatic beta-cells responses to nutrient
stimuli and hormonal modulators include multiple messengers and
signaling pathways with complex interdependencies. Here we present a
computational model that incorporates recent data on glucose
metabolism, plasma membrane potential, G-protein-coupled-receptors
(GPCR), cytoplasmic and endoplasmic reticulum calcium dynamics, cAMP
and phospholipase C pathways that regulate interactions between second
messengers in pancreatic beta-cells. The values of key model
parameters were inferred from published experimental data. The model
gives a reasonable fit to important aspects of experimentally measured
metabolic and second messenger concentrations and provides a framework
for analyzing the role of metabolic, hormones and neurotransmitters
changes on insulin secretion. Our analysis of the dynamic data
provides support for the hypothesis that activation of Ca2+-dependent
adenylyl cyclases play a critical role in modulating the effects of
glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic
polypeptide (GIP) and catecholamines. ..." |
| 9. |
Regulation of KCNQ2/KCNQ3 current by G protein cycling (Suh et al 2004)
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Receptor-mediated modulation of KCNQ channels regulates neuronal excitability. This study concerns
the kinetics and mechanism of M1 muscarinic receptor-mediated regulation of the cloned neuronal M channel, KCNQ2/KCNQ3 (Kv7.2/Kv7.3). ... observations were successfully described by a kinetic model representing biochemical steps of the signaling
cascade using published rate constants where available. The model supports the following sequence of events for
this Gq-coupled signaling: A classical G-protein cycle, including competition for nucleotide-free G-protein by all
nucleotide forms and an activation step requiring Mg2, followed by G-protein-stimulated phospholipase C and
hydrolysis of PIP2, and finally PIP2 dissociation from binding sites for inositol lipid on the channels so that KCNQ
current was suppressed. See paper for details and more. |
| 10. |
Signaling pathways In D1R containing striatal spiny projection neurons (Blackwell et al 2018)
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We implemented a mechanistic model of signaling pathways activated by dopamine D1 receptors, acetylcholine receptors, and glutamate. We use our novel, computationally efficient simulator, NeuroRD, to simulate stochastic interactions both within and between dendritic spines. Results show that the combined activity of several key plasticity molecules correctly predicts the occurrence of either LTP, LTD or no plasticity for numerous experimental protocols. |
| 11. |
Striatal D1R medium spiny neuron, including a subcellular DA cascade (Lindroos et al 2018)
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We are investigating how dopaminergic modulation of single channels can be combined to make the D1R possitive MSN more excitable. We also connect multiple channels to substrates of a dopamine induced subcellular cascade to highlight that the classical pathway is too slow to explain DA induced kinetics in the subsecond range (Howe and Dombeck, 2016. doi: 10.1038/nature18942) |
