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| Models | Description |
| 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). | |
| 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." | |
| 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. | |
| 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." | |
| 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 | |
| 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. | |
| 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 | |
| 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. | |
| 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. | |
| 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. | |
| 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. | |
| 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. | |
| 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. | |
| 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) | |
| 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. | |
| 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. | |
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