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Models that contain the Current : I L high threshold

("Long-lasting"; slowly inactivating; threshold around -20 mV)

   Models   Description
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.
A multi-compartment model for interneurons in the dLGN (Halnes et al. 2011)
This model for dLGN interneurons is presented in two parameterizations (P1 & P2), which were fitted to current-clamp data from two different interneurons (IN1 & IN2). The model qualitatively reproduces the responses in IN1 & IN2 under 8 different experimental condition, and quantitatively reproduces the I/O-relations (#spikes elicited as a function of injected current).
A network model of tail withdrawal in Aplysia (White et al 1993)
The contributions of monosynaptic and polysynaptic circuitry to the tail-withdrawal reflex in the marine mollusk Aplysia californica were assessed by the use of physiologically based neural network models. Effects of monosynaptic circuitry were examined by the use of a two-layer network model with four sensory neurons in the input layer and one motor neuron in the output layer. Results of these simulations indicated that the monosynaptic circuit could not account fully for long-duration responses of tail motor neurons elicited by tail stimulation. A three-layer network model was constructed by interposing a layer of two excitatory interneurons between the input and output layers of the two-layer network model. The three-layer model could account for long-duration responses in motor neurons. Sensory neurons are a known site of plasticity in Aplysia. Synaptic plasticity at more than one locus modified dramatically the input-output relationship of the three-layer network model. This feature gave the model redundancy in its plastic properties and points to the possibility of distributed memory in the circuitry mediating withdrawal reflexes in Aplysia. Please see paper for more results and details.
A single column thalamocortical network model (Traub et al 2005)
To better understand population phenomena in thalamocortical neuronal ensembles, we have constructed a preliminary network model with 3,560 multicompartment neurons (containing soma, branching dendrites, and a portion of axon). Types of neurons included superficial pyramids (with regular spiking [RS] and fast rhythmic bursting [FRB] firing behaviors); RS spiny stellates; fast spiking (FS) interneurons, with basket-type and axoaxonic types of connectivity, and located in superficial and deep cortical layers; low threshold spiking (LTS) interneurons, that contacted principal cell dendrites; deep pyramids, that could have RS or intrinsic bursting (IB) firing behaviors, and endowed either with non-tufted apical dendrites or with long tufted apical dendrites; thalamocortical relay (TCR) cells; and nucleus reticularis (nRT) cells. To the extent possible, both electrophysiology and synaptic connectivity were based on published data, although many arbitrary choices were necessary.
A two-layer biophysical olfactory bulb model of cholinergic neuromodulation (Li and Cleland 2013)
This is a two-layer biophysical olfactory bulb (OB) network model to study cholinergic neuromodulation. Simulations show that nicotinic receptor activation sharpens mitral cell receptive field, while muscarinic receptor activation enhances network synchrony and gamma oscillations. This general model suggests that the roles of nicotinic and muscarinic receptors in OB are both distinct and complementary to one another, together regulating the effects of ascending cholinergic inputs on olfactory bulb transformations.
Activity dependent changes in motoneurones (Dai Y et al 2002, Gardiner et al 2002)
These two papers review various experimental papers and examine the effects of activity on motoneurons in a similar 5 compartment model with 10 active conductances. Included are slow (S) and fast (F) type and fast fatigue resistant (FR) and fast fatigable (FF) models corresponding to the types of motoneurons. See papers for more and details.
Activity dependent conductances in a neuron model (Liu et al. 1998)
"... We present a model of a stomatogastric ganglion (STG) neuron in which several Ca2+-dependent pathways are used to regulate the maximal conductances of membrane currents in an activity-dependent manner. Unlike previous models of this type, the regulation and modification of maximal conductances by electrical activity is unconstrained. The model has seven voltage-dependent membrane currents and uses three Ca2+ sensors acting on different time scales. ... The model suggests that neurons may regulate their conductances to maintain fixed patterns of electrical activity, rather than fixed maximal conductances, and that the regulation process requires feedback systems capable of reacting to changes of electrical activity on a number of different time scales."
Afferent Integration in the NAcb MSP Cell (Wolf et al. 2005)
"We describe a computational model of the principal cell in the nucleus accumbens (NAcb), the medium spiny projection (MSP) neuron. The model neuron, constructed in NEURON, includes all of the known ionic currents in these cells and receives synaptic input from simulated spike trains via NMDA, AMPA, and GABAA receptors. ... results suggest that afferent information integration by the NAcb MSP cell may be compromised by pathology in which the NMDA current is altered or modulated, as has been proposed in both schizophrenia and addiction."
Amyloid beta (IA block) effects on a model CA1 pyramidal cell (Morse et al. 2010)
The model simulations provide evidence oblique dendrites in CA1 pyramidal neurons are susceptible to hyper-excitability by amyloid beta block of the transient K+ channel, IA. See paper for details.
An integrative model of the cardiac ventricular myocytes (Greenstein and Winslow 2002)
The local control theory of excitation-contraction (EC) coupling in cardiac muscle asserts that L-type Ca2+ current tightly controls Ca2+ release from the sarcoplasmic reticulum (SR) via local interaction of closely apposed L-type Ca2+ channels (LCCs) and ryanodine receptors (RyRs). ...In this study we present a biophysically detailed model of the normal canine ventricular myocyte that conforms to local control theory. The model formulation incorporates details of microscopic EC coupling properties in the form of Ca2+ release units (CaRUs) in which individual sarcolemmal LCCs interact in a stochastic manner with nearby RyRs in localized regions ... See paper for more and details.
AP back-prop. explains threshold variability and rapid rise (McCormick et al. 2007, Yu et al. 2008)
This simple axon-soma model explained how the rapid rising phase in the somatic spike is derived from the propagated axon initiated spike, and how the somatic spike threshold variance is affected by spike propagation.
Axonal NaV1.6 Sodium Channels in AP Initiation of CA1 Pyramidal Neurons (Royeck et al. 2008)
"... We show that the Na+ channel NaV1.6 displays a striking aggregation at the AIS of cortical neurons. ... In combination with simulations using a realistic computer model of a CA1 pyramidal cell, our results imply that a hyperpolarized voltage-dependence of activation of AIS NaV1.6 channels is important both in determining spike threshold and localizing spike initiation to the AIS. ... These results suggest that NaV1.6 subunits at the AIS contribute significantly to its role as spike trigger zone and shape repetitive discharge properties of CA1 neurons."
Axonal Projection and Interneuron Types (Helmstaedter et al. 2008)
"Interneurons in layer 2/3 (L2/3) of the somatosensory cortex show 4 types of axonal projection patterns with reference to the laminae and borders of columns in rat barrel cortex (Helmstaedter et al. 2008a). Here, we analyzed the dendritic geometry and electrical excitability of these interneurons. ... We conclude that 1) dendritic polarity is correlated to intrinsic electrical excitability, and 2) the axonal projection pattern represents an independent classifier of interneurons. "
CA1 pyramidal neuron: as a 2-layer NN and subthreshold synaptic summation (Poirazi et al 2003)
We developed a CA1 pyramidal cell model calibrated with a broad spectrum of in vitro data. Using simultaneous dendritic and somatic recordings, and combining results for two different response measures (peak vs. mean EPSP), two different stimulus formats (single shock vs. 50 Hz trains), and two different spatial integration conditions (within vs. between-branch summation), we found the cell's subthreshold responses to paired inputs are best described as a sum of nonlinear subunit responses, where the subunits correspond to different dendritic branches. In addition to suggesting a new type of experiment and providing testable predictions, our model shows how conclusions regarding synaptic arithmetic can be influenced by an array of seemingly innocuous experimental design choices.
CA1 pyramidal neuron: synaptically-induced bAP predicts synapse location (Sterratt et al. 2012)
This is an adaptation of Poirazi et al.'s (2003) CA1 model that is used to measure BAP-induced voltage and calcium signals in spines after simulated Schaffer collateral synapse stimulation. In the model, the peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. There are also simulations demonstrating that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value.
CA3 pyramidal cell: rhythmogenesis in a reduced Traub model (Pinsky, Rinzel 1994)
Fig. 2A and 3 are reproduced in this simulation of Pinsky PF, Rinzel J (1994).
CA3 pyramidal neuron (Lazarewicz et al 2002)
The model shows how using a CA1-like distribution of active dendritic conductances in a CA3 morphology results in dendritic initiation of spikes during a burst.
CA3 Pyramidal Neuron (Migliore et al 1995)
Model files from the paper: M. Migliore, E. Cook, D.B. Jaffe, D.A. Turner and D. Johnston, Computer simulations of morphologically reconstructed CA3 hippocampal neurons, J. Neurophysiol. 73, 1157-1168 (1995). Demonstrates how the same cell could be bursting or non bursting according to the Ca-independent conductance densities. Includes calculation of intracellular Calcium. Instructions are provided in the below README file. Contact if you have any questions about the implementation of the model.
CA3 pyramidal neuron (Safiulina et al. 2010)
In this review some of the recent work carried out in our laboratory concerning the functional role of GABAergic signalling at immature mossy fibres (MF)-CA3 principal cell synapses has been highlighted. To compare the relative strength of CA3 pyramidal cell output in relation to their MF glutamatergic or GABAergic inputs in postnatal development, a realistic model was constructed taking into account the different biophysical properties of these synapses.
CA3 pyramidal neuron: firing properties (Hemond et al. 2008)
In the paper, this model was used to identify how relative differences in K+ conductances, specifically KC, KM, & KD, between cells contribute to the different characteristics of the three types of firing patterns observed experimentally.
Calcium and potassium currents of olfactory bulb juxtaglomerular cells (Masurkar and Chen 2011)
Inward and outward currents of the olfactory bulb juxtaglomerular cells are characterized in the experiments and modeling in these two Masurkar and Chen 2011 papers.
Calcium influx during striatal upstates (Evans et al. 2013)
"... To investigate the mechanisms that underlie the relationship between calcium and AP timing, we have developed a realistic biophysical model of a medium spiny neuron (MSN). ... Using this model, we found that either the slow inactivation of dendritic sodium channels (NaSI) or the calcium inactivation of voltage-gated calcium channels (CDI) can cause high calcium corresponding to early APs and lower calcium corresponding to later APs. We found that only CDI can account for the experimental observation that sensitivity to AP timing is dependent on NMDA receptors. Additional simulations demonstrated a mechanism by which MSNs can dynamically modulate their sensitivity to AP timing and show that sensitivity to specifically timed pre- and postsynaptic pairings (as in spike timing-dependent plasticity protocols) is altered by the timing of the pairing within the upstate. …"
Calcium response prediction in the striatal spines depending on input timing (Nakano et al. 2013)
We construct an electric compartment model of the striatal medial 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.
Calcium spikes in basal dendrites (Kampa and Stuart 2006)
This model was published in Kampa & Stuart (2006) J Neurosci 26(28):7424-32. The simulation creates two plots showing voltage and calcium changes in basal dendrites of layer 5 pyramidal neurons during action potential backpropagation. created by B. Kampa (2006)
Calcium waves and mGluR-dependent synaptic plasticity in CA1 pyr. neurons (Ashhad & Narayanan 2013)
A morphologically realistic, conductance-based model equipped with kinetic schemes that govern several calcium signalling modules and pathways in CA1 pyramidal neurons
Cardiac Atrial Cell (Courtemanche et al 1998)
Marc Courtemanche, Rafael J. Ramirez, and Stanley Nattel. Ionic mechanisms underlying human atrial action potential properties insights from a mathematical model Am J Physiol Heart Circ Physiol 1998 275: H301-H321. The implementation of this model in NEURON was contributed by Ingemar Jacobson.
Cardiac Atrial Cell (Courtemanche et al 1998) (C++)
The mechanisms underlying many important properties of the human atrial action potential (AP) are poorly understood. Using specific formulations of the K+, Na+, and Ca2+ currents based on data recorded from human atrial myocytes, along with representations of pump, exchange, and background currents, we developed a mathematical model of the AP. The model AP resembles APs recorded from human atrial samples and responds to rate changes, L-type Ca2+ current blockade, Na+/Ca2+ exchanger inhibition, and variations in transient outward current amplitude in a fashion similar to experimental recordings. Rate-dependent adaptation of AP duration, an important determinant of susceptibility to atrial fibrillation, was attributable to incomplete L-type Ca2+ current recovery from inactivation and incomplete delayed rectifier current deactivation at rapid rates. Experimental observations of variable AP morphology could be accounted for by changes in transient outward current density, as suggested experimentally. We conclude that this mathematical model of the human atrial AP reproduces a variety of observed AP behaviors and provides insights into the mechanisms of clinically important AP properties.
CN bushy, stellate neurons (Rothman, Manis 2003)
Using kinetic data from three different K+ currents in acutely isolated neurons, a single electrical compartment model representing the soma of a ventral cochlear nucleus (VCN) neuron was created. The K+ currents include a fast transient current (IA), a slow-inactivating low-threshold current (ILT), and a noninactivating high-threshold current (IHT). The model also includes a fast-inactivating Na+ current, a hyperpolarization-activated cation current (Ih), and 1-50 auditory nerve synapses. With this model, the role IA, ILT, and IHT play in shaping the discharge patterns of VCN cells is explored. Simulation results indicate these currents have specific roles in shaping the firing patterns of stellate and bushy CN cells. (see readme.txt and the papers, esp 2003c, for details). Any questions regarding these implementations should be directed to: 2 April 2004 Paul B Manis, Ph.D.
CN bushy, stellate neurons (Rothman, Manis 2003) (Brian)
Cochlear neuron model of Rothman & Manis (2003). Adapted from the Neuron implementation.
Compartmentalization of GABAergic inhibition by dendritic spines (Chiu et al. 2013)
A spiny dendrite model supports the hypothesis that only inhibitory inputs on spine heads, not shafts, compartmentalizes inhibition of calcium signals to spine heads as seen in paired inhibition with back-propagating action potential experiments on prefrontal cortex layer 2/3 pyramidal neurons in mouse (Chiu et al. 2013).
Complex CA1-neuron to study AP initiation (Wimmer et al. 2010)
Complex model of a pyramidal CA1-neuron, adapted from Royeck, M., et al. Role of axonal NaV1.6 sodium channels in action potential initiation of CA1 pyramidal neurons. Journal of neurophysiology 100, 2361-2380 (2008). It contains a biophysically realistic morphology comprising 265 compartments (829 segments) and 15 different distributed Ca2+- and/or voltage-dependent conductances.
Dendritic L-type Ca currents in motoneurons (Carlin et al 2000)
A component of recorded currents demonstrated kinetics consistent with a current originating at a site spatially segregated from the soma. In response to step commands this component was seen as a late-onset, low amplitude persistent current whilst in response to depolarizing-repolarizing ramp commands a low voltage clockwise current hysteresis was recorded. Simulations using a neuromorphic motoneuron model could reproduce these currents only if a noninactivating calcium conductance was placed in the dendritic compartments.
Dendritic processing of excitatory synaptic input in GnRH neurons (Roberts et al. 2006)
"... we used electrophysiological recordings and neuronal reconstructions to generate computer models of (Gonadotopin-Releasing Hormone) GnRH neurons to examine the effects of synaptic inputs at varying distances from the soma along dendrites. ... analysis of reduced morphology models indicated that this population of cells is unlikely to exhibit low-frequency tonic spiking in the absence of synaptic input. ... applying realistic patterns of synaptic input to modeled GnRH neurons indicates that synapses located more than about 30% of the average dendrite length from the soma cannot drive firing at frequencies consistent with neuropeptide release. Thus, processing of synaptic input to dendrites of GnRH neurons is probably more complex than simple summation."
Dendritica (Vetter et al 2001)
Dendritica is a collection of programs for relating dendritic geometry and signal propagation. The programs are based on those used for the simulations described in: Vetter, P., Roth, A. & Hausser, M. (2001) For reprint requests and additional information please contact Dr. M. Hausser, email address:
Dentate gyrus granule cell: calcium and calcium-dependent conductances (Aradi and Holmes 1999)
We have constructed a detailed model of a hippocampal dentate granule (DG) cell that includes nine different channel types. Channel densities and distributions were chosen to reproduce reported physiological responses observed in normal solution and when blockers were applied. The model was used to explore the contribution of each channel type to spiking behavior with particular emphasis on the mechanisms underlying postspike events. ... The model was used to predict changes in channel densities that could lead to epileptogenic burst discharges and to predict the effect of altered buffering capacity on firing behavior. We conclude that the clustered spatial distributions of calcium related channels, the presence of slow delayed rectifier potassium currents in dendrites, and calcium buffering properties, together, might explain the resistance of DG cells to the development of epileptogenic burst discharges.
Dentate gyrus network model (Santhakumar et al 2005)
Mossy cell loss and mossy fiber sprouting are two characteristic consequences of repeated seizures and head trauma. However, their precise contributions to the hyperexcitable state are not well understood. Because it is difficult, and frequently impossible, to independently examine using experimental techniques whether it is the loss of mossy cells or the sprouting of mossy fibers that leads to dentate hyperexcitability, we built a biophysically realistic and anatomically representative computational model of the dentate gyrus to examine this question. The 527-cell model, containing granule, mossy, basket, and hilar cells with axonal projections to the perforant-path termination zone, showed that even weak mossy fiber sprouting (10-15% of the strong sprouting observed in the pilocarpine model of epilepsy) resulted in the spread of seizure-like activity to the adjacent model hippocampal laminae after focal stimulation of the perforant path. See reference for more and details.
Differential modulation of pattern and rate in a dopamine neuron model (Canavier and Landry 2006)
"A stylized, symmetric, compartmental model of a dopamine neuron in vivo shows how rate and pattern can be modulated either concurrently or differentially. If two or more parameters in the model are varied concurrently, the baseline firing rate and the extent of bursting become decorrelated, which provides an explanation for the lack of a tight correlation in vivo and is consistent with some independence of the mechanisms that generate baseline firing rates versus bursting. ..." See paper for more and details.
Dynamic cortical interlaminar interactions (Carracedo et al. 2013)
"... Here we demonstrate the mechanism underlying a purely neocortical delta rhythm generator and show a remarkable laminar, cell subtype and local subcircuit delineation between delta and nested theta rhythms. We show that spike timing during delta-nested theta rhythms controls an iterative, reciprocal interaction between deep and superficial cortical layers resembling the unsupervised learning processes proposed for laminar neural networks by Hinton and colleagues ... and mimicking the alternating cortical dynamics of sensory and memory processing during wakefulness."
Dynamical model of olfactory bulb mitral cell (Rubin, Cleland 2006)
This four-compartment mitral cell exhibits endogenous subthreshold oscillations, phase resetting, and evoked spike phasing properties as described in electrophysiological studies of mitral cells. It is derived from the prior work of Davison et al (2000) and Bhalla and Bower (1993). See readme.txt for details.
Effects of Acetyl-L-carnitine on neural transmission (Lombardo et al 2004)
Acetyl-L-carnitine is known to improve many aspects of the neural activity even if its exact role in neurotransmission is still unknown. This study investigates the effects of acetyl-L-carnitine in T segmental sensory neurons of the leech Hirudo medicinalis. These neurons are involved in some forms of neural plasticity associated with learning processes. Their physiological firing is accompanied by a large afterhyperpolarization that is mainly due to the Na+/K+ ATPase activity and partially to a Ca2+-dependent K+ current. A clear-cut hyperpolarization and a significant increase of the afterhyperpolarization have been recorded in T neurons of leeches injected with 2 mM acetyl-L-carnitine some days before. Acute treatments of 50 mM acetyl-L-carnitine induced similar effects in T cells of naive animals. Moreover, in these cells, widely arborized, the afterhyperpolarization seems to play an important role in determining the action potential transmission at neuritic bifurcations. A computational model of a T cell has been previously developed considering detailed data for geometry and the modulation of the pump current. Herein, we showed that to a larger afterhyperpolarization, due to the acetyl-L-carnitine-induced effects, corresponds a decrement in the number of action potentials reaching synaptic terminals.
Effects of KIR current inactivation in NAc Medium Spiny Neurons (Steephen and Manchanda 2009)
"Inward rectifying potassium (KIR) currents in medium spiny (MS) neurons of nucleus accumbens inactivate significantly in ~40% of the neurons but not in the rest, which may lead to differences in input processing by these two groups. Using a 189-compartment computational model of the MS neuron, we investigate the influence of this property using injected current as well as spatiotemporally distributed synaptic inputs. Our study demonstrates that KIR current inactivation facilitates depolarization, firing frequency and firing onset in these neurons. ..."
Enhanced Excitability in Hermissenda: modulation by 5-HT (Cai et al 2003)
Serotonin (5-HT) applied to the exposed but otherwise intact nervous system results in enhanced excitability of Hermissenda type-B photoreceptors. Several ion currents in the type-B photoreceptors are modulated by 5-HT, including the A-type K+ current (IK,A), sustained Ca2+ current (ICa,S), Ca-dependent K+ current (IK,Ca), and a hyperpolarization-activated inward rectifier current (Ih). In this study,we developed a computational model that reproduces physiological characteristics of type B photoreceptors, e.g. resting membrane potential, dark-adapted spike activity, spike width, and the amplitude difference between somatic and axonal spikes. We then used the model to investigate the contribution of different ion currents modulated by 5-HT to the magnitudes of enhanced excitability produced by 5-HT. See paper for results and more details.
ERG current in repolarizing plateau potentials in dopamine neurons (Canavier et al 2007)
"Blocking the small-conductance (SK) calcium-activated potassium channel promotes burst firing in dopamine neurons both in vivo and in vitro. ... We focus on the underlying plateau potential oscillation generated in the presence of both apamin and TTX, so that action potentials are not considered. We find that although the plateau potentials are mediated by a voltage-gated Ca2+ current, they do not depend on the accumulation of cytosolic Ca2+, then use a computational model to test the hypothesis that the slowly voltage-activated ether-a-go-go–related gene (ERG) potassium current repolarizes the plateaus. The model, which includes a material balance on calcium, is able to reproduce the time course of both membrane potential and somatic calcium concentration, and can also mimic the induction of plateau potentials by the calcium chelator BAPTA." See paper for more.
Excitability of PFC Basal Dendrites (Acker and Antic 2008)
".. We carried out multi-site voltage-sensitive dye imaging of membrane potential transients from thin basal branches of prefrontal cortical pyramidal neurons before and after application of channel blockers. We found that backpropagating action potentials (bAPs) are predominantly controlled by voltage-gated sodium and A-type potassium channels. In contrast, pharmacologically blocking the delayed rectifier potassium, voltage-gated calcium or Ih, conductance had little effect on dendritic action potential propagation. Optically recorded bAP waveforms were quantified and multicompartmental modeling (NEURON) was used to link the observed behavior with the underlying biophysical properties. The best-fit model included a non-uniform sodium channel distribution with decreasing conductance with distance from the soma, together with a non-uniform (increasing) A-type potassium conductance. AP amplitudes decline with distance in this model, but to a lesser extent than previously thought. We used this model to explore the mechanisms underlying two sets of published data involving high frequency trains of action potentials, and the local generation of sodium spikelets. ..."
Excitation-contraction coupling/mitochondrial energetics (ECME) model (Cortassa et al. 2006)
"An intricate network of reactions is involved in matching energy supply with demand in the heart. This complexity arises because energy production both modulates and is modulated by the electrophysiological and contractile activity of the cardiac myocyte. Here, we present an integrated mathematical model of the cardiac cell that links excitation-contraction coupling with mitochondrial energy generation. The dynamics of the model are described by a system of 50 ordinary differential equations. The formulation explicitly incorporates cytoplasmic ATP-consuming processes associated with force generation and ion transport, as well as the creatine kinase reaction. Changes in the electrical and contractile activity of the myocyte are coupled to mitochondrial energetics through the ATP, Ca21, and Na1 concentrations in the myoplasmic and mitochondrial matrix compartments. ..."
Fast oscillations in inhibitory networks (Maex, De Schutter 2003)
We observed a new phenomenon of resonant synchronization in computer-simulated networks of inhibitory neurons in which the synaptic current has a delayed onset, reflecting finite spike propagation and synaptic transmission times. At the resonant level of network excitation, all neurons fire synchronously and rhythmically with a period approximately four times the mean delay of the onset of the inhibitory synaptic current. ... By varying the axonal delay of the inhibitory connections, networks with a realistic synaptic kinetics can be tuned to frequencies from 40 to >200 Hz. ... We conclude that the delay of the synaptic current is the primary parameter controlling the oscillation frequency of inhibitory networks and propose that delay-induced synchronization is a mechanism for fast brain rhythms that depend on intact inhibitory synaptic transmission.
Global structure, robustness, and modulation of neuronal models (Goldman et al. 2001)
"The electrical characteristics of many neurons are remarkably robust in the face of changing internal and external conditions. At the same time, neurons can be highly sensitive to neuromodulators. We find correlates of this dual robustness and sensitivity in a global analysis of the structure of a conductance-based model neuron. ..."
Globus pallidus multi-compartmental model neuron with realistic morphology (Gunay et al. 2008)
"Globus pallidus (GP) neurons recorded in brain slices show significant variability in intrinsic electrophysiological properties. To investigate how this variability arises, we manipulated the biophysical properties of GP neurons using computer simulations. ... Our results indicated that most of the experimental variability could be matched by varying conductance densities, which we confirmed with additional partial block experiments. Further analysis resulted in two key observations: (1) each voltage-gated conductance had effects on multiple measures such as action potential waveform and spontaneous or stimulated spike rates; and (2) the effect of each conductance was highly dependent on the background context of other conductances present. In some cases, such interactions could reverse the effect of the density of one conductance on important excitability measures. ..."
Hodgkin-Huxley model of persistent activity in PFC neurons (Winograd et al. 2008) (NEURON python)
The paper demonstrate a form of graded persistent activity activated by hyperpolarization. This phenomenon is modeled based on a slow calcium regulation of Ih, similar to that introduced earlier for thalamic neurons (see Destexhe et al., J Neurophysiol. 1996). The only difference is that the calcium signal is here provided by the high-threshold calcium current (instead of the low-threshold calcium current in thalamic neurons).
Hodgkin-Huxley model of persistent activity in prefrontal cortex neurons (Winograd et al. 2008)
The paper demonstrate a form of graded persistent activity activated by hyperpolarization. This phenomenon is modeled based on a slow calcium regulation of Ih, similar to that introduced earlier for thalamic neurons (see Destexhe et al., J Neurophysiol. 1996). The only difference is that the calcium signal is here provided by the high-threshold calcium current (instead of the low-threshold calcium current in thalamic neurons).
Hodgkin-Huxley models of different classes of cortical neurons (Pospischil et al. 2008)
"We review here the development of Hodgkin– Huxley (HH) type models of cerebral cortex and thalamic neurons for network simulations. The intrinsic electrophysiological properties of cortical neurons were analyzed from several preparations, and we selected the four most prominent electrophysiological classes of neurons. These four classes are “fast spiking”, “regular spiking”, “intrinsically bursting” and “low-threshold spike” cells. For each class, we fit “minimal” HH type models to experimental data. ..."
Hysteresis in voltage gating of HCN channels (Elinder et al 2006, Mannikko et al 2005)
We found that HCN2 and HCN4 channels expressed in oocytes from the frog Xenopus laevis do not display the activation kinetic changes that we (previously) observed in spHCN and HCN1. However, HCN2 and HCN4 channels display changes in their tail currents, suggesting that these channels also undergo mode shifts and that the conformational changes underlying the mode shifts are due to conserved aspects of HCN channels. With computer modelling, we show that in channels with relatively slow opening kinetics and fast mode-shift transitions, such as HCN2 and HCN4 channels, the mode shift effects are not readily observable, except in the tail kinetics. Computer simulations of sino-atrial node action potentials suggest that the HCN2 channel, together with the HCN1 channel, are important regulators of the heart firing frequency and that the mode shift is an important property to prevent arrhythmic firing. We conclude that although all HCN channels appear to undergo mode shifts – and thus may serve to prevent arrhythmic firing – it is mainly observable in ionic currents from HCN channels with faster kinetics. See papers for more and details.
Impact of dendritic atrophy on intrinsic and synaptic excitability (Narayanan & Chattarji, 2010)
These simulations examined the atrophy induced changes in electrophysiological properties of CA3 pyramidal neurons. We found these neurons change from bursting to regular spiking as atrophy increases. Region-specific atrophy induced region-specific increases in synaptic excitability in a passive dendritic tree. All dendritic compartments of an atrophied neuron had greater synaptic excitability and a larger voltage transfer to the soma than the control neuron.
Intracortical synaptic potential modulation by presynaptic somatic potential (Shu et al. 2006, 2007)
" ... Here we show that the voltage fluctuations associated with dendrosomatic synaptic activity propagate significant distances along the axon, and that modest changes in the somatic membrane potential of the presynaptic neuron modulate the amplitude and duration of axonal action potentials and, through a Ca21- dependent mechanism, the average amplitude of the postsynaptic potential evoked by these spikes. These results indicate that synaptic activity in the dendrite and soma controls not only the pattern of action potentials generated, but also the amplitude of the synaptic potentials that these action potentials initiate in local cortical circuits, resulting in synaptic transmission that is a mixture of triggered and graded (analogue) signals."
Ionic basis of alternans and Timothy Syndrome (Fox et al. 2002), (Zhu and Clancy 2007)
From Zhu and Clancy: "... Here we employ theoretical simulations to examine the effects of a Timothy Syndrome (TS) mutation in the L-type Ca2+ channel on cardiac dynamics over multiple scales, from a gene mutation to protein, cell, tissue, and finally the ECG, to connect a defective Ca2+ channel to arrhythmia susceptibility. ..."
Ionic mechanisms of bursting in CA3 pyramidal neurons (Xu and Clancy 2008)
"... We present a single-compartment model of a CA3 hippocampal pyramidal neuron based on recent experimental data. We then use the model to determine the roles of primary depolarizing currents in burst generation. The single compartment model incorporates accurate representations of sodium (Na+) channels (NaV1.1) and T-type calcium (Ca2+) channel subtypes (CaV3.1, CaV3.2, and CaV3.3). Our simulations predict the importance of Na+ and T-type Ca2+ channels in hippocampal pyramidal cell bursting and reveal the distinct contribution of each subtype to burst morphology. We also performed fastslow analysis in a reduced comparable model, which shows that our model burst is generated as a result of the interaction of two slow variables, the T-type Ca2+ channel activation gate and the Ca2+-dependent potassium (K+) channel activation gate. The model reproduces a range of experimentally observed phenomena including afterdepolarizing potentials, spike widening at the end of the burst, and rebound. Finally, we use the model to simulate the effects of two epilepsy-linked mutations: R1648H in NaV1.1 and C456S in CaV3.2, both of which result in increased cellular excitability."
Irregular spiking in NMDA-driven prefrontal cortex neurons (Durstewitz and Gabriel 2006)
Slow N-Methyl-D-aspartic acid (NMDA) synaptic currents are assumed to strongly contribute to the persistently elevated firing rates observed in prefrontal cortex (PFC) during working memory. During persistent activity, spiking of many neurons is highly irregular. ... The highest interspike-interval (ISI) variability occurred in a transition regime where the subthreshold membrane potential distribution shifts from mono- to bimodality, ... Predictability within irregular ISI series was significantly higher than expected from a noise-driven linear process, indicating that it might best be described through complex (potentially chaotic) nonlinear deterministic processes. Accordingly, the phenomena observed in vitro could be reproduced in purely deterministic biophysical model neurons. High spiking irregularity in these models emerged within a chaotic, close-to-bifurcation regime characterized by a shift of the membrane potential distribution from mono- to bimodality and by similar ISI return maps as observed in vitro. ... NMDA-induced irregular dynamics may have important implications for computational processes during working memory and neural coding.
Ketamine disrupts theta modulation of gamma in a computer model of hippocampus (Neymotin et al 2011)
"Abnormalities in oscillations have been suggested to play a role in schizophrenia. We studied theta-modulated gamma oscillations in a computer model of hippocampal CA3 in vivo with and without simulated application of ketamine, an NMDA receptor antagonist and psychotomimetic. Networks of 1200 multi-compartment neurons (pyramidal, basket and oriens-lacunosum moleculare, OLM, cells) generated theta and gamma oscillations from intrinsic network dynamics: basket cells primarily generated gamma and amplified theta, while OLM cells strongly contributed to theta. ..."
KV1 channel governs cerebellar output to thalamus (Ovsepian et al. 2013)
The output of the cerebellum to the motor axis of the central nervous system is orchestrated mainly by synaptic inputs and intrinsic pacemaker activity of deep cerebellar nuclear (DCN) projection neurons. Herein, we demonstrate that the soma of these cells is enriched with KV1 channels produced by mandatory multi-merization of KV1.1, 1.2 alpha andKV beta2 subunits. Being constitutively active, the K+ current (IKV1) mediated by these channels stabilizes the rate and regulates the temporal precision of self-sustained firing of these neurons. ... Through the use of multi-compartmental modelling and ... the physiological significance of the described functions for processing and communication of information from the lateral DCN to thalamic relay nuclei is established.
Kv4.3, Kv1.4 encoded K channel in heart cells & tachy. (Winslow et al 1999, Greenstein et al 2000)
(1999) We present a model of the canine midmyocardial ventricular action potential and Ca2+ transient. The model is used to estimate the degree of functional upregulation and downregulation of Na/Ca exchanger protein and sarcoplasmic reticulum Ca ATPase in heart failure using data obtained from 2 different experimental protocols. (2000): A model of canine I:(to1) (the Ca(2+)-independent transient outward current) is formulated as the combination of Kv4.3 and Kv1.4 currents and is incorporated into an existing canine ventricular myocyte model. Simulations demonstrate strong coupling between L-type Ca(2+) current and I:(Kv4.3) and predict a bimodal relationship between I:(Kv4.3) density and APD whereby perturbations in I:(Kv4.3) density may produce either prolongation or shortening of APD, depending on baseline I:(to1) current level. See each paper for more and details.
L5b PC model constrained for BAC firing and perisomatic current step firing (Hay et al., 2011)
"... L5b pyramidal cells have been the subject of extensive experimental and modeling studies, yet conductance-based models of these cells that faithfully reproduce both their perisomatic Na+-spiking behavior as well as key dendritic active properties, including Ca2+ spikes and back-propagating action potentials, are still lacking. Based on a large body of experimental recordings from both the soma and dendrites of L5b pyramidal cells in adult rats, we characterized key features of the somatic and dendritic firing and quantified their statistics. We used these features to constrain the density of a set of ion channels over the soma and dendritic surface via multi-objective optimization with an evolutionary algorithm, thus generating a set of detailed conductance-based models that faithfully replicate the back-propagating action potential activated Ca2+ spike firing and the perisomatic firing response to current steps, as well as the experimental variability of the properties. ... The models we present provide several experimentally-testable predictions and can serve as a powerful tool for theoretical investigations of the contribution of single-cell dynamics to network activity and its computational capabilities. "
Lateral dendrodenditic inhibition in the Olfactory Bulb (David et al. 2008)
Mitral cells, the principal output neurons of the olfactory bulb, receive direct synaptic activation from primary sensory neurons. Shunting inhibitory inputs delivered by granule cell interneurons onto mitral cell lateral dendrites are believed to influence spike timing and underlie coordinated field potential oscillations. Lateral dendritic shunt conductances delayed spiking to a degree dependent on both their electrotonic distance and phase of onset. Recurrent inhibition significantly narrowed the distribution of mitral cell spike times, illustrating a tendency towards coordinated synchronous activity. This result suggests an essential role for early mechanisms of temporal coordination in olfaction. The model was adapted from Davison et al, 2003, but include additional noise mechanisms, long lateral dendrite, and specific synaptic point processes.
Layer V PFC pyramidal neuron used to study persistent activity (Sidiropoulou & Poirazi 2012)
"... Here, we use a compartmental modeling approach to search for discriminatory features in the properties of incoming stimuli to a PFC pyramidal neuron and/or its response that signal which of these stimuli will result in persistent activity emergence. Furthermore, we use our modeling approach to study cell-type specific differences in persistent activity properties, via implementing a regular spiking (RS) and an intrinsic bursting (IB) model neuron. ... Collectively, our results pinpoint to specific features of the neuronal response to a given stimulus that code for its ability to induce persistent activity and predict differential roles of RS and IB neurons in persistent activity expression. "
Leech S Cell: Modulation of Excitability by Serotonin (Burrell and Crisp 2007)
Serotonergic modulation of the afterhyperpolarization (AHP) contributes to the regulation of the excitability of the leech S cell, a neuron critical for sensitization of the shortening reflex. Pharmacological and physiological data suggest that three currents contribute to the S cell's afterhyperpolarization: a charybdotoxin-sensitive, fast calcium-dependent potassium current (fAHP); a tubocurare-sensitive, calcium-dependent potassium current (mAHP); and, a saxitoxin-sensitive, afterdepolarization current (ADP). This single-compartment model of the S cell is constructed using fAHP, mAHP and ADP currents, and shows that reduction of the conductances to mimic the effects of serotonin is sufficient to enhance excitability (repetitive firing). Burrell BD, Crisp KM (2007) Serotonergic modulation of afterhyperpolarization in a neuron that contributes to learning in the leech. J Neurophysiol, in press.
Mathematical model for windup (Aguiar et al. 2010)
"Windup is characterized as a frequency-dependent increase in the number of evoked action potentials in dorsal horn neurons in response to electrical stimulation of afferent C-fibers. ... The approach presented here relies on mathematical and computational analysis to study the mechanism(s) underlying windup. From experimentally obtained windup profiles, we extract the time scale of the facilitation mechanisms that may support the characteristics of windup. Guided by these values and using simulations of a biologically realistic compartmental model of a wide dynamic range (WDR) neuron, we are able to assess the contribution of each mechanism for the generation of action potentials windup. ..."
Mechanisms of fast rhythmic bursting in a layer 2/3 cortical neuron (Traub et al 2003)
This simulation is based on the reference paper listed below.

This port was made by Roger D Traub and Maciej T Lazarewicz ( Thanks to Ashlen P Reid for help with porting a morphology of the cell.

Medial vestibular neuron models (Quadroni and Knopfel 1994)
The structure and the parameters of the model cells were chosen to reproduce the responses of type A and type B MVNns as described in electrophysiological recordings. The emergence of oscillatory firing under these two specific experimental conditions is consistent with electrophysiological recordings not used during construction of the model. We, therefore, suggest that these models have a high predictive value.
Modelling reduced excitability in aged CA1 neurons as a Ca-dependent process (Markaki et al. 2005)
"We use a multi-compartmental model of a CA1 pyramidal cell to study changes in hippocampal excitability that result from aging-induced alterations in calcium-dependent membrane mechanisms. The model incorporates N- and L-type calcium channels which are respectively coupled to fast and slow afterhyperpolarization potassium channels. Model parameters are calibrated using physiological data. Computer simulations reproduce the decreased excitability of aged CA1 cells, which results from increased internal calcium accumulation, subsequently larger postburst slow afterhyperpolarization, and enhanced spike frequency adaptation. We find that aging-induced alterations in CA1 excitability can be modelled with simple coupling mechanisms that selectively link specific types of calcium channels to specific calcium-dependent potassium channels."
MyFirstNEURON (Houweling, Sejnowski 1997)
MyFirstNEURON is a NEURON demo by Arthur Houweling and Terry Sejnowski. Perform experiments from the book 'Electrophysiology of the Neuron, A Companion to Shepherd's Neurobiology, An Interactive Tutorial' by John Huguenard & David McCormick, Oxford University Press 1997, or design your own one or two cell simulation. For more information see Salk Institute, Computational Neurobiology Lab, 10010 North Torrey Pines Rd., La Jolla CA 092037. Email:
Neocortical pyramidal neuron: deep; effects of dopamine (Durstewitz et al 2000)
"... Simulated dopamine strongly enhanced high, delay-type activity but not low, spontaneous activity in the model network. Furthermore the strength of an afferent stimulation needed to disrupt delay-type activity increased with the magnitude of the dopamine-induced shifts in network parameters, making the currently active representation much more stable. Stability could be increased by dopamine-induced enhancements of the persistent Na(+) and N-methyl-D-aspartate (NMDA) conductances. Stability also was enhanced by a reduction in AMPA conductances. The increase in GABA(A) conductances that occurs after stimulation of dopaminergic D1 receptors was necessary in this context to prevent uncontrolled, spontaneous switches into high-activity states (i.e., spontaneous activation of task-irrelevant representations). In conclusion, the dopamine-induced changes in the biophysical properties of intrinsic ionic and synaptic conductances conjointly acted to highly increase stability of activated representations in PFC networks and at the same time retain control over network behavior and thus preserve its ability to adequately respond to task-related stimuli. ..." See paper and references for more and details.
Network model of the granular layer of the cerebellar cortex (Maex, De Schutter 1998)
We computed the steady-state activity of a large-scale model of the granular layer of the rat cerebellum. Within a few tens of milliseconds after the start of random mossy fiber input, the populations of Golgi and granule cells became entrained in a single synchronous oscillation, the basic frequency of which ranged from 10 to 40 Hz depending on the average rate of firing in the mossy fiber population. ... The synchronous, rhythmic firing pattern was robust over a broad range of biologically realistic parameter values and to parameter randomization. Three conditions, however, made the oscillations more transient and could desynchronize the entire network in the end: a very low mossy fiber activity, a very dominant excitation of Golgi cells through mossy fiber synapses (rather than through parallel fiber synapses), and a tonic activation of granule cell GABAA receptors (with an almost complete absence of synaptically induced inhibitory postsynaptic currents). The model predicts that, under conditions of strong mossy fiber input to the cerebellum, Golgi cells do not only control the strength of parallel fiber activity but also the timing of the individual spikes. Provided that their parallel fiber synapses constitute an important source of excitation, Golgi cells fire rhythmically and synchronized with granule cells over large distances along the parallel fiber axis. See paper for more and details.
NMDA subunit effects on Calcium and STDP (Evans et al. 2012)
Effect of NMDA subunit on spike timing dependent plasticity.
O-LM interneuron model (Lawrence et al. 2006)
Exploring the kinetics and distribution of the muscarinic potassium channel, IM, in 2 O-LM interneuron morphologies. Modulation of the ion channel by drugs such as XE991 (antagonist) and retigabine (agonist) are simulated in the models to examine the role of IM in spiking properties.
Olfactory bulb mitral cell gap junction NN model: burst firing and synchrony (O`Connor et al. 2012)
In a network of 6 mitral cells connected by gap junction in the apical dendrite tuft, continuous current injections of 0.06 nA are injected into 20 locations in the apical tufts of two of the mitral cells. The current injections into one of the cells starts 10 ms after the other to generate asynchronous firing in the cells (Migliore et al. 2005 protocol). Firing of the cells is asynchronous for the first 120 ms. However after the burst firing phase is completed the firing in all cells becomes synchronous.
Olfactory Bulb Network (Davison et al 2003)
A biologically-detailed model of the mammalian olfactory bulb, incorporating the mitral and granule cells and the dendrodendritic synapses between them. The results of simulation experiments with electrical stimulation agree closely in most details with published experimental data. The model predicts that the time course of dendrodendritic inhibition is dependent on the network connectivity as well as on the intrinsic parameters of the synapses. In response to simulated odor stimulation, strongly activated mitral cells tend to suppress neighboring cells, the mitral cells readily synchronize their firing, and increasing the stimulus intensity increases the degree of synchronization. For more details, see the reference below.
Olfactory Mitral Cell (Bhalla, Bower 1993)
This is a conversion to NEURON of the mitral cell model described in Bhalla and Bower (1993). The original model was written in GENESIS and is available by joining BABEL, the GENESIS users' group.
Olfactory Mitral Cell (Davison et al 2000)
A four-compartment model of a mammalian olfactory bulb mitral cell, reduced from the complex 286-compartment model described by Bhalla and Bower (1993). The compartments are soma/axon, secondary dendrites, primary dendrite shaft and primary dendrite tuft. The reduced model runs 75 or more times faster than the full model, making its use in large, realistic network models of the olfactory bulb practical.
Paradoxical GABA-mediated excitation (Lewin et al. 2012)
"GABA is the key inhibitory neurotransmitter in the adult central nervous system, but in some circumstances can lead to a paradoxical excitation that has been causally implicated in diverse pathologies from endocrine stress responses to diseases of excitability including neuropathic pain and temporal lobe epilepsy. We undertook a computational modeling approach to determine plausible ionic mechanisms of GABAA-dependent excitation in isolated post-synaptic CA1 hippocampal neurons because it may constitute a trigger for pathological synchronous epileptiform discharge. In particular, the interplay intracellular chloride accumulation via the GABAA receptor and extracellular potassium accumulation via the K/Cl co-transporter KCC2 in promoting GABAA-mediated excitation is complex. ..."
Parameter estimation for Hodgkin-Huxley based models of cortical neurons (Lepora et al. 2011)
Simulation and fitting of two-compartment (active soma, passive dendrite) for different classes of cortical neurons. The fitting technique indirectly matches neuronal currents derived from somatic membrane potential data rather than fitting the voltage traces directly. The method uses an analytic solution for the somatic ion channel maximal conductances given approximate models of the channel kinetics, membrane dynamics and dendrite. This approach is tested on model-derived data for various cortical neurons.
Permeation and inactivation of CaV1.2 Ca2+ channels (Babich et al. 2007)
The authors present data and a kinetics model of the CaV1.2 channel supporting the idea that Ca2+ block of the pore generates the U-shaped inactivation curve.
Preserving axosomatic spiking features despite diverse dendritic morphology (Hay et al., 2013)
The authors found that linearly scaling the ion channel conductance densities of a reference model with the conductance load in 28 3D reconstructed layer 5 thick-tufted pyramidal cells was necessary to match the experimental statistics of these cells electrical firing properties.
Pyramidal Neuron Deep: Constrained by experiment (Dyhrfjeld-Johnsen et al. 2005)
"... As a practical demonstration of the use of CoCoDat we constructed a detailed computer model of an intrinsically bursting (IB) layer V pyramidal neuron from the rat barrel cortex supplementing experimental data (Schubert et al., 2001) with information extracted from the database. The pyramidal neuron morphology (Fig. 10B) was reconstructed from histological sections of a biocytin-stained IB neuron using the NeuroLucida software package..."
Rapid desynchronization of an electrically coupled Golgi cell network (Vervaeke et al. 2010)
Electrical synapses between interneurons contribute to synchronized firing and network oscillations in the brain. However, little is known about how such networks respond to excitatory synaptic input. In addition to detailed electrophysiological recordings and histological investigations of electrically coupled Golgi cells in the cerebellum, a detailed network model of these cells was created. The cell models are based on reconstructed Golgi cell morphologies and the active conductances are taken from an earlier abstract Golgi cell model (Solinas et al 2007, accession no. 112685). Our results show that gap junction coupling can sometimes be inhibitory and either promote network synchronization or trigger rapid network desynchronization depending on the synaptic input. The model is available as a neuroConstruct project and can executable scripts can be generated for the NEURON simulator.
Rat phrenic motor neuron (Amini et al 2004)
We have developed a model for the rat phrenic motor neuron (PMN) that robustly replicates many experimentally observed behaviors of PMNs in response to pharmacological, ionic, and electrical perturbations using a single set of parameters.
Rat subthalamic projection neuron (Gillies and Willshaw 2006)
A computational model of the rat subthalamic nucleus projection neuron is constructed using electrophysiological and morphological data and a restricted set of channel specifications. The model cell exhibits a wide range of electrophysiological behaviors characteristic of rat subthalamic neurons. It reveals that a key set of three channels play a primary role in distinguishing behaviors: a high-voltage-activated calcium channel (Cav 1.2.-1.3), a low-voltage-activated calcium channel (Cav 3.-), and a small current calcium-activated potassium channel (KCa 2.1-2.3). See paper for more and details.
Regulation of firing frequency in a midbrain dopaminergic neuron model (Kuznetsova et al. 2010)
A dopaminergic (DA) neuron model with a morphologicaly realistic dendritic architecture. The model captures several salient features of DA neurons under different pharmacological manipulations and exhibits depolarization block for sufficiently high current pulses applied to the soma.
Retinal Ganglion Cell: I-CaN and I-CaL (Benison et al. 2001)
NEURON mod files for the CaN and CaL currents from the papers: Huang, S.-J. & Robinson, D.W. (1998). Activation and Inactivation properties of voltage-gated calcium currents in developing cat retinal ganglion cells. Neuroscience 85:239-247 (experimental) and Benison G. Keizer J., Chalupa L.M., Robinson D.W., (2001) J. theor. Biol. 210:187-199 (theoretical).
Ribbon Synapse (Sikora et al 2005)
A model of the ribbon synapse was developed to replicate both pre- and postsynaptic functions of this glutamatergic juncture. The presynaptic portion of the model is rich in anatomical and physiological detail and includes multiple release sites for each ribbon based on anatomical studies of presynaptic terminals, presynaptic voltage at the terminal, the activation of voltage-gated calcium channels and a calcium-dependent release mechanism whose rate varies as a function of the calcium concentration that is monitored at two different sites which control both an ultrafast, docked pool of vesicles and a release ready pool of tethered vesicles. See paper for more and details.
Simulated light response in rod photoreceptors (Liu and Kourennyi 2004)
We developed a complete computer model of the rod, which accurately reproduced the main features of the light response and allowed us to demonstrate that it was suppression of Kx channels that was essential for slowing SLR and increasing excitability of rods. The results reported in this work further establish the importance of Kx channels in rod photoreceptor function.
Simulation study of Andersen-Tawil syndrome (Sung et al 2006)
Patients with Andersen-Tawil syndrome (ATS) mostly have mutations on the KCNJ2 gene producing loss of function or dominant-negative suppression of the inward rectifier K(+) channel Kir2.1. However, clinical manifestations of ATS including dysmorphic features, periodic paralysis (hypo-, hyper-, or normokalemic), long QT, and ventricular arrhythmias (VA) are considerably variable. Using a modified dynamic Luo-Rudy simulation model of cardiac ventricular myocyte, we elucidate the mechanisms of VA in ATS. We adopted a kinetic model of KCNJ2 in which channel block by Mg(+2) and spermine was incorporated. In this study, we attempt to examine the effects of KCNJ2 mutations on the ventricular action potential (AP), single-channel Markovian models were reformulated and incorporated into the dynamic Luo-Rudy model for rapidly and slowly delayed rectifying K(+) currents and KCNJ2 channel. During pacing at 1.0 Hz with [K(+)]o at 5.4 mM, a stepwise 10% reduction of Kir2.1 channel conductance progressively prolonged the terminal repolarization phase of AP along with gradual depolarization of the resting membrane potential (RMP). At 90% reduction, early after- depolarizations (EADs) became inducible and RMP was depolarized to -55.0 mV (control: -90.1 mV) followed by emergence of spontaneous action potentials (SAP). Both EADs and SAP were facilitated by a decrease in [K(+)]o and suppressed by increase in [K(+)]o. beta-adrenergic stimulation enhanced delayed after-depolarizations (DADs) and could also facilitate EADs as well as SAP in the setting of low [K(+)]o and reduced Kir2.1 channel conductance. In conclusion, the spectrum of VA in ATS includes (1) triggered activity mediated by EADs and/or DADs, and (2) abnormal automaticity manifested as SAP. These VA can be aggravated by a decrease in [K(+)]o and beta-adrenergic stimulation, and may potentially induce torsades de pointes and cause sudden death. In patients with ATS, the hypokalemic form of periodic paralysis should have the highest propensity to VA especially during physical activities.
Sleep-wake transitions in corticothalamic system (Bazhenov et al 2002)
The authors investigate the transition between sleep and awake states with intracellular recordings in cats and computational models. The model describes many essential features of slow wave sleep and activated states as well as the transition between them.
STD-dependent and independent encoding of Input irregularity as spike rate (Luthman et al. 2011)
"... We use a conductance-based model of a CN neuron to study the effect of the regularity of Purkinje cell spiking on CN neuron activity. We find that increasing the irregularity of Purkinje cell activity accelerates the CN neuron spike rate and that the mechanism of this recoding of input irregularity as output spike rate depends on the number of Purkinje cells converging onto a CN neuron. ..."
STDP depends on dendritic synapse location (Letzkus et al. 2006)
This model was published in Letzkus, Kampa & Stuart (2006) J Neurosci 26(41):10420-9. The simulation creates several plots showing voltage and NMDA current and conductance changes at different apical dendritic locations in layer 5 pyramidal neurons during STDP induction protocols. Created by B. Kampa (2006).
Study of augmented Rubin and Terman 2004 deep brain stim. model in Parkinsons (Pascual et al. 2006)
" ... The model by Rubin and Terman [31] represents one of the most comprehensive and biologically plausible models of DBS published recently. We examined the validity of the model, replicated its simulations and tested its robustness. While our simulations partially reproduced the results presented by Rubin and Terman [31], several issues were raised including the high complexity of the model in its non simplified form, the lack of robustness of the model with respect to small perturbations, the nonrealistic representation of the thalamus and the absence of time delays. Computational models are indeed necessary, but they may not be sufficient in their current forms to explain the effect of chronic electrical stimulation on the activity of the basal ganglia (BG) network in PD."
Synaptic integration in a model of granule cells (Gabbiani et al 1994)
We have developed a compartmental model of a turtle cerebellar granule cell consisting of 13 compartments that represent the soma and 4 dendrites. We used this model to investigate the synaptic integration of mossy fiber inputs in granule cells. See reference or abstract at PubMed link below for more information.
Synaptic integration in tuft dendrites of layer 5 pyramidal neurons (Larkum et al. 2009)
Simulations used in the paper. Voltage responses to current injections in different tuft locations; NMDA and calcium spike generation. Summation of multiple input distribution.
Temporal decorrelation by intrinsic cellular dynamics (Wang et al 2003)
"... Recent investigations in primary visual (V1) cortical neurons have demonstrated that adaptation to prolonged changes in stimulus contrast is mediated in part through intrinsic ionic currents, a Ca2+ activated K+ current (IKCa) and especially a Na+ activated K+ current (IKNa). The present study was designed to test the hypothesis that the activation of adaptation ionic currents may provide a cellular mechanism for temporal decorrelation in V1. A conductance-based neuron model was simulated, which included an IKCa and an IKNa. We show that the model neuron reproduces the adaptive behavior of V1 neurons in response to high contrast inputs. ...". See paper for details and more.
Thalamic interneuron multicompartment model (Zhu et al. 1999)
this is an attempt to recreate a set of simulations originally performed in 1994 under NEURON version 3 and last tested in 1999. When I ran it now it did not behave exactly the same as previously which I suspect is due to some minor mod file changes on my side rather than due to any differences among versions. After playing around with the parameters a little bit I was able to get something that looks generally like a physiological trace in J Neurophysiol, 81:702--711, 1999, fig. 8b top trace. This sad preface is simply offered in order to encourage anyone who is interested in this model to make and post fixes. I'm happy to help out. Simulation by JJ Zhu To run nrnivmodl nrngui.hoc
Thalamic neuron: Modeling rhythmic neuronal activity (Meuth et al. 2005)
The authors use an in vitro cell model of a single acutely isolated thalamic neuron in the NEURON simulation environment to address and discuss questions in an undergraduate course. Topics covered include passive electrical properties, composition of action potentials, trains of action potentials, multicompartment modeling, and research topics. The paper includes detailed instructions on how to run the simulations in the appendix.
Theta phase precession in a model CA3 place cell (Baker and Olds 2007)
"... The present study concerns a neurobiologically based computational model of the emergence of theta phase precession in which the responses of a single model CA3 pyramidal cell are examined in the context of stimulation by realistic afferent spike trains including those of place cells in entorhinal cortex, dentate gyrus, and other CA3 pyramidal cells. Spike-timing dependent plasticity in the model CA3 pyramidal cell leads to a spatially correlated associational synaptic drive that subsequently creates a spatially asymmetric expansion of the model cell’s place field. ... Through selective manipulations of the model it is possible to decompose theta phase precession in CA3 into the separate contributing factors of inheritance from upstream afferents in the dentate gyrus and entorhinal cortex, the interaction of synaptically controlled increasing afferent drive with phasic inhibition, and the theta phase difference between dentate gyrus granule cell and CA3 pyramidal cell activity."
Touch Sensory Cells (T Cells) of the Leech (Cataldo et al. 2004) (Scuri et al. 2007)
Bursts of spikes in leech T cells produce an AHP, which results from activation of a Na+/K+ pump and a Ca2+-dependent K+ current. Activity-dependent increases in the AHP are believed to induce conduction block of spikes in several regions of the neuron, which in turn, may decrease presynaptic invasion of spikes and thereby decrease transmitter release. To explore this possibility, we used the neurosimulator SNNAP to develop a multi-compartmental model of the T cell. Each compartment was modeled as an equivalent electrical circuit, in which some currents were regulated by intracellular Ca2+ and Na+. The membrane model consisted of a membrane capacitance (Cm), for which we used the value 1 uF/cm2, in parallel with two inward currents (Na+ and Ca2+), two K+ currents, a leak current and pump current. The model incorporated empirical data that describe the geometry of the cell and activity-dependent changes of the AHP (see paper for details). Simulations indicated that at some branching points, activity-dependent increases of the AHP reduced the number of spikes transmitted from the minor receptive field to the soma and beyond. These results suggest that the AHP can regulate spike conduction within the presynaptic arborizations of the cell and could in principle contribute to the synaptic depression that is correlated with increases in the AHP.
Turtle visual cortex model (Nenadic et al. 2003, Wang et al. 2005, Wang et al. 2006)
This is a model of the visual cortex of freshwater turtles that is based upon the known anatomy and physiology of individual neurons. The model was published in three papers (Nenadic et al., 2003; Wang et al., 2005; Wang et al., 2006), which should be consulted for full details on its construction. The model has also been used in several papers (Robbins and Senseman, 2004; Du et al., 2005; Du et al., 2006). It is implemented in GENESIS (Bower and Beeman, 1998).
Ventricular cell model (Guinea-pig-type) (Luo, Rudy 1991, +10 other papers!) (C++)
A mathematical model of the membrane action potential of the mammalian ventricular cell is introduced. The model is based, whenever possible, on recent single-cell and single-channel data and incorporates the possibility of changing extracellular potassium concentration [K]o. ... The results are consistent with recent experimental observations, and the model simulations relate these phenomena to the underlying ionic channel kinetics. See paper for more and details.

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