Models that contain the Receptor : Monoamine Receptors

Re-display model names without descriptions
    Models   Description
1.  A 1000 cell network model for Lateral Amygdala (Kim et al. 2013)
1000 Cell Lateral Amygdala model for investigation of plasticity and memory storage during Pavlovian Conditioning.
2.  A basal ganglia model of aberrant learning (Ursino et al. 2018)
A comprehensive, biologically inspired neurocomputational model of action selection in the Basal Ganglia allows simulation of dopamine induced aberrant learning in Parkinsonian subjects. In particular, the model simulates the Alternate Finger Tapping motor task as an indicator of bradykinesia.
3.  A contracting model of the basal ganglia (Girard et al. 2008)
Basal ganglia model : selection processes between channels, dynamics controlled by contraction analysis, rate-coding model of neurons based on locally projected dynamical systems (lPDS).
4.  A kinetic model of dopamine- and calcium-dependent striatal synaptic plasticity (Nakano et al. 2010)
A signaling pathway model of spines that express D1-type dopamine receptors was constructed to analyze the dynamic mechanisms of dopamine- and calcium-dependent plasticity. The model incorporated all major signaling molecules, including dopamine- and cyclic AMP-regulated phosphoprotein with a molecular weight of 32 kDa (DARPP32), as well as AMPA receptor trafficking in the post-synaptic membrane. Simulations with dopamine and calcium inputs reproduced dopamine- and calcium-dependent plasticity. Further in silico experiments revealed that the positive feedback loop consisted of protein kinase A (PKA), protein phosphatase 2A (PP2A), and the phosphorylation site at threonine 75 of DARPP-32 (Thr75) served as the major switch for inducing LTD and LTP. The present model elucidated the mechanisms involved in bidirectional regulation of corticostriatal synapses and will allow for further exploration into causes and therapies for dysfunctions such as drug addiction."
5.  A neural model of Parkinson`s disease (Cutsuridis and Perantonis 2006, Cutsuridis 2006, 2007)
"A neural model of neuromodulatory (dopamine) control of arm movements in Parkinson’s disease (PD) bradykinesia was recently introduced [1, 2]. The model is multi-modular consisting of a basal ganglia module capable of selecting the most appropriate motor command in a given context, a cortical module for coordinating and executing the final motor commands, and a spino-musculo-skeletal module for guiding the arm to its final target and providing proprioceptive (feedback) input of the current state of the muscle and arm to higher cortical and lower spinal centers. ... The new (extended) model [3] predicted that the reduced reciprocal disynaptic Ia inhibition in the DA depleted case doesn’t lead to the co-contraction of antagonist motor units." See below readme and papers for more and details.
6.  Altered complexity in layer 2/3 pyramidal neurons (Luuk van der Velden et al. 2012)
" ... Our experimental results show that hypercomplexity of the apical dendritic tuft of layer 2/3 pyramidal neurons affects neuronal excitability by reducing the amount of spike frequency adaptation. This difference in firing pattern, related to a higher dendritic complexity, was accompanied by an altered development of the afterhyperpolarization slope with successive action potentials. Our abstract and realistic neuronal models, which allowed manipulation of the dendritic complexity, showed similar effects on neuronal excitability and confirmed the impact of apical dendritic complexity. Alterations of dendritic complexity, as observed in several pathological conditions such as neurodegenerative diseases or neurodevelopmental disorders, may thus not only affect the input to layer 2/3 pyramidal neurons but also shape their firing pattern and consequently alter the information processing in the cortex."
7.  Application of a common kinetic formalism for synaptic models (Destexhe et al 1994)
Application to AMPA, NMDA, GABAA, and GABAB receptors is given in a book chapter. The reference paper synthesizes a comprehensive general description of synaptic transmission with Markov kinetic models. This framework is applicable to modeling ion channels, synaptic release, and all receptors. Please see the references for more details. A simple introduction to this method is given in a seperate paper Destexhe et al Neural Comput 6:14-18 , 1994). More information and papers at http://cns.iaf.cnrs-gif.fr/Main.html and through email: Destexhe@iaf.cnrs-gif.fr
8.  Basal Ganglia and Levodopa Pharmacodynamics model for parameter estimation in PD (Ursino et al 2020)
Parkinson disease (PD) is characterized by a clear beneficial motor response to levodopa (LD) treatment. However, with disease progression and longer LD exposure, drug-related motor fluctuations usually occur. Recognition of the individual relationship between LD concentration and its effect may be difficult, due to the complexity and variability of the mechanisms involved. This work proposes an innovative procedure for the automatic estimation of LD pharmacokinetics and pharmacodynamics parameters, by a biologically-inspired mathematical model. An original issue, compared with previous similar studies, is that the model comprises not only a compartmental description of LD pharmacokinetics in plasma and its effect on the striatal neurons, but also a neurocomputational model of basal ganglia action selection. Parameter estimation was achieved on 26 patients (13 with stable and 13 with fluctuating LD response) to mimic plasma LD concentration and alternate finger tapping frequency along four hours after LD administration, automatically minimizing a cost function of the difference between simulated and clinical data points. Results show that individual data can be satisfactorily simulated in all patients and that significant differences exist in the estimated parameters between the two groups. Specifically, the drug removal rate from the effect compartment, and the Hill coefficient of the concentration-effect relationship were significantly higher in the fluctuating than in the stable group. The model, with individualized parameters, may be used to reach a deeper comprehension of the PD mechanisms, mimic the effect of medication, and, based on the predicted neural responses, plan the correct management and design innovative therapeutic procedures.
9.  CA1 pyramidal cell receptor dependent cAMP dynamics (Chay et al. 2016)
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.
10.  Calcium response prediction in the striatal spines depending on input timing (Nakano et al. 2013)
We construct an electric compartment model of the striatal medium spiny neuron with a realistic morphology and predict the calcium responses in the synaptic spines with variable timings of the glutamatergic and dopaminergic inputs and the postsynaptic action potentials. The model was validated by reproducing the responses to current inputs and could predict the electric and calcium responses to glutamatergic inputs and back-propagating action potential in the proximal and distal synaptic spines during up and down states.
11.  Compartmental differences in cAMP signaling pathways in hippocam. CA1 pyr. cells (Luczak et al 2017)
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.
12.  Cortico-striatal plasticity in medium spiny neurons (Gurney et al 2015)
In the associated paper (Gurney et al, PLoS Biology, 2015) we presented a computational framework that addresses several issues in cortico-striatal plasticity including spike timing, reward timing, dopamine level, and dopamine receptor type. Thus, we derived a complete model of dopamine and spike-timing dependent cortico-striatal plasticity from in vitro data. We then showed this model produces the predicted activity changes necessary for learning and extinction in an operant task. Moreover, we showed the complex dependencies of cortico-striatal plasticity are not only sufficient but necessary for learning and extinction. The model was validated in a wider setting of action selection in basal ganglia, showing how it could account for behavioural data describing extinction, renewal, and reacquisition, and replicate in vitro experimental data on cortico-striatal plasticity. The code supplied here allows reproduction of the proposed process of learning in medium spiny neurons, giving the results of Figure 7 of the paper.
13.  D2 dopamine receptor modulation of interneuronal activity (Maurice et al. 2004)
"... Using a combination of electrophysiological, molecular, and computational approaches, the studies reported here show that D2 dopamine receptor modulation of Na+ currents underlying autonomous spiking contributes to a slowing of discharge rate, such as that seen in vivo. Four lines of evidence support this conclusion. ... Fourth, simulation of cholinergic interneuron pacemaking revealed that a modest increase in the entry of Na+ channels into the slow-inactivated state was sufficient to account for the slowing of pacemaker discharge. These studies establish a cellular mechanism linking dopamine and the reduction in striatal cholinergic interneuron activity seen in the initial stages of associative learning." See paper for more and details.
14.  Dopamine activation of signaling pathways in a medium spiny projection neuron (Oliveira et al. 2012)
Large scale stochastic reaction-diffusion model of signaling pathways in a medium spiny projection neuron dendrite with spines to investigate whether the critical function of anchoring is to locate PKA near the cAMP that activates it or near its targets, such as AMPA receptors located in the post-synaptic density. Simulations, implemented in NeuroRD, show that PKA colocalization with adenylate cyclase, either in the spine head or in the dendrite, leads to greater phosphorylation of DARPP-32 Thr34 and AMPA receptor GluA1 Ser845 than when PKA is anchored away from adenylate cyclase.
15.  Dopamine-modulated medium spiny neuron, reduced model (Humphries et al. 2009)
We extended Izhikevich's reduced model of the striatal medium spiny neuron (MSN) to account for dopaminergic modulation of its intrinsic ion channels and synaptic inputs. We tuned our D1 and D2 receptor MSN models using data from a recent (Moyer et al, 2007) large-scale compartmental model. Our new models capture the input-output relationships for both current injection and spiking input with remarkable accuracy, despite the order of magnitude decrease in system size. They also capture the paired pulse facilitation shown by MSNs. Our dopamine models predict that synaptic effects dominate intrinsic effects for all levels of D1 and D2 receptor activation. Our analytical work on these models predicts that the MSN is never bistable. Nonetheless, these MSN models can produce a spontaneously bimodal membrane potential similar to that recently observed in vitro following application of NMDA agonists. We demonstrate that this bimodality is created by modelling the agonist effects as slow, irregular and massive jumps in NMDA conductance and, rather than a form of bistability, is due to the voltage-dependent blockade of NMDA receptors
16.  Dynamic dopamine modulation in the basal ganglia: Learning in Parkinson (Frank et al 2004,2005)
See README file for all info on how to run models under different tasks and simulated Parkinson's and medication conditions.
17.  Effect of cortical D1 receptor sensitivity on working memory maintenance (Reneaux & Gupta 2018)
Alterations in cortical D1 receptor density and reactivity of dopamine-binding sites, collectively termed as D1 receptor-sensitivity in the present study, have been experimentally shown to affect the working memory maintenance during delay-period. However, computational models addressing the effect of D1 receptor-sensitivity are lacking. A quantitative neural mass model of the prefronto-mesoprefrontal system has been proposed to take into account the effect of variation in cortical D1 receptor-sensitivity on working memory maintenance during delay. The model computes the delay-associated equilibrium states/operational points of the system for different values of D1 receptor-sensitivity through the nullcline and bifurcation analysis. Further, to access the robustness of the working memory maintenance during delay in the presence of alteration in D1 receptor-sensitivity, numerical simulations of the stochastic formulation of the model are performed to obtain the global potential landscape of the dynamics.
18.  Gamma genesis in the basolateral amygdala (Feng et al 2019)
Using in vitro and in vivo data we develop the first large-scale biophysically and anatomically realistic model of the basolateral amygdala nucleus (BL), which reproduces the dynamics of the in vivo local field potential (LFP). Significantly, it predicts that BL intrinsically generates the transient gamma oscillations observed in vivo. The model permitted exploration of the poorly understood synaptic mechanisms underlying gamma genesis in BL, and the model's ability to compute LFPs at arbitrary numbers of recording sites provided insights into the characteristics of the spatial properties of gamma bursts. Furthermore, we show how gamma synchronizes principal cells to overcome their low firing rates while simultaneously promoting competition, potentially impacting their afferent selectivity and efferent drive, and thus emotional behavior.
19.  Hippocampus CA1: Simulations of LTP signaling pathways (Kim M et al. 2011)
This is a multi-compartmental, stochastic version of the Kim et al. 2010 paper. There are a few additional reactions, and some of the rate constants have been updated. It addresses the role of molecule anchoring in PKA dependent hippocampal LTP.
20.  Hippocampus CA1: Temporal sensitivity of signaling pathways underlying LTP (Kim et al. 2010)
Temporal sensitivity of signaling pathways underlying L-LTP. Single compartment, deterministic model of calcium and dopamine activated pathways, leading to CaMKII and PKA activation. Experimental verification of model prediction.
21.  Model of DARPP-32 phosphorylation in striatal medium spiny neurons (Lindskog et al. 2006)
The work describes a model of how transient calcium and dopamine inputs might affect phosphorylation of DARPP-32 in the medium spiny neurons in the striatum. The model is relevant for understanding both the "three-factor rule" for synaptic plasticity in corticostriatal synapses, and also for relating reinforcement learning theories to biology.
22.  Modeling a Nociceptive Neuro-Immune Synapse Activated by ATP and 5-HT in Meninges (Suleimanova et al., 2020)
"Extracellular ATP and serotonin (5-HT) are powerful triggers of nociceptive firing in the meninges, a process supporting headache and whose cellular mechanisms are incompletely understood. The current study aimed to develop, with the neurosimulator NEURON, a novel approach to explore in silico the molecular determinants of the long-lasting, pulsatile nature of migraine attacks. The present model included ATP and 5-HT release, ATP diffusion and hydrolysis, 5-HT uptake, differential activation of ATP P2X or 5-HT3 receptors, and receptor subtype-specific desensitization. The model also tested the role of branched meningeal fibers with multiple release sites. Spike generation and propagation were simulated using variable contribution by potassium and sodium channels in a multi-compartment fiber environment. Multiple factors appeared important to ensure prolonged nociceptive firing potentially relevant to long-lasting pain. Crucial roles were observed in: (i) co-expression of ATP P2X2 and P2X3 receptor subunits; (ii) intrinsic activation/inactivation properties of sodium Nav1.8 channels; and (iii) temporal and spatial distribution of ATP/5-HT release sites along the branches of trigeminal nerve fibers. Based on these factors we could obtain either persistent activation of nociceptive firing or its periodic bursting mimicking the pulsating nature of pain. In summary, our model proposes a novel tool for the exploration of peripheral nociception to test the contribution of clinically relevant factors to headache including migraine pain." (paper abstract)
23.  Modeling interactions in Aplysia neuron R15 (Yu et al 2004)
"The biophysical properties of neuron R15 in Aplysia endow it with the ability to express multiple modes of oscillatory electrical activity, such as beating and bursting. Previous modeling studies examined the ways in which membrane conductances contribute to the electrical activity of R15 and the ways in which extrinsic modulatory inputs alter the membrane conductances by biochemical cascades and influence the electrical activity. The goals of the present study were to examine the ways in which electrical activity influences the biochemical cascades and what dynamical properties emerge from the ongoing interactions between electrical activity and these cascades." See paper for more and details.
24.  Pancreatic Beta Cell signalling pathways (Fridlyand & Philipson 2016) (MATLAB)
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. ..."
25.  Reproducing infra-slow oscillations with dopaminergic modulation (Kobayashi et al 2017)
" ... In this paper, to reproduce ISO (Infra-Slow Oscillations) in neural networks, we show that dopaminergic modulation of STDP is essential. More specifically, we discovered a close relationship between two dopaminergic effects: modulation of the STDP function and generation of ISO. We therefore, numerically investigated the relationship in detail and proposed a possible mechanism by which ISO is generated."
26.  Signaling pathways In D1R containing striatal spiny projection neurons (Blackwell et al 2018)
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.
27.  Spiking neuron model of the basal ganglia (Humphries et al 2006)
A spiking neuron model of the basal ganglia (BG) circuit (striatum, STN, GP, SNr). Includes: parallel anatomical channels; tonic dopamine; dopamine receptors in striatum, STN, and GP; burst-firing in STN; GABAa, AMPA, and NMDA currents; effects of synaptic location. Model demonstrates selection and switching of input signals. Replicates experimental data on changes in slow-wave (<1 Hz) and gamma-band oscillations within BG nuclei following lesions and pharmacological manipulations.
28.  Spiny neuron model with dopamine-induced bistability (Gruber et al 2003)
These files implement a model of dopaminergic modulation of voltage-gated currents (called kir2 and caL in the original paper). See spinycell.html for details of usage and implementation. For questions about this implementation, contact Ted Carnevale (ted.carnevale@yale.edu)
29.  Striatal D1R medium spiny neuron, including a subcellular DA cascade (Lindroos et al 2018)
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)
30.  Striatal FSI and SPN oscillation model (Chartove et al. 2020)
Our model consists of three interconnected populations of single or double compartment Hodgkin-Huxley neurons: a feedforward network of FSIs, and two networks of SPNs (the D1 receptor-expressing "direct pathway" subnetwork and the D2 receptor-expressing "indirect pathway" subnetwork).
31.  Striatal GABAergic microcircuit, dopamine-modulated cell assemblies (Humphries et al. 2009)
To begin identifying potential dynamically-defined computational elements within the striatum, we constructed a new three-dimensional model of the striatal microcircuit's connectivity, and instantiated this with our dopamine-modulated neuron models of the MSNs and FSIs. A new model of gap junctions between the FSIs was introduced and tuned to experimental data. We introduced a novel multiple spike-train analysis method, and apply this to the outputs of the model to find groups of synchronised neurons at multiple time-scales. We found that, with realistic in vivo background input, small assemblies of synchronised MSNs spontaneously appeared, consistent with experimental observations, and that the number of assemblies and the time-scale of synchronisation was strongly dependent on the simulated concentration of dopamine. We also showed that feed-forward inhibition from the FSIs counter-intuitively increases the firing rate of the MSNs.
32.  Striatal GABAergic microcircuit, spatial scales of dynamics (Humphries et al, 2010)
The main thrust of this paper was the development of the 3D anatomical network of the striatum's GABAergic microcircuit. We grew dendrite and axon models for the MSNs and FSIs and extracted probabilities for the presence of these neurites as a function of distance from the soma. From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks. These networks were examined for their predictions for the distributions of the numbers and distances of connections for all the connections in the microcircuit. We then combined the neuron models from a previous model (Humphries et al, 2009; ModelDB ID: 128874) with the new anatomical model. We used this new complete striatal model to examine the impact of the anatomical network on the firing properties of the MSN and FSI populations, and to study the influence of all the inputs to one MSN within the network.
33.  Striatal NN model of MSNs and FSIs investigated effects of dopamine depletion (Damodaran et al 2015)
This study investigates the mechanisms that are affected in the striatal network after dopamine depletion and identifies potential therapeutic targets to restore normal activity.
34.  Two forms of synaptic depression by neuromodulation of presynaptic Ca2+ channels (Burke et al 2018)
"... To determine whether the different biophysical mechanisms of CaV modulation predicted by OFA (Optical Fluctuation Analysis) are sufficient to explain the differing effects of D1Rs and GABA B Rs on STP, we developed a reduced synaptic model..."

Re-display model names without descriptions