Models that contain the Gene Name : HCN1

(hyperpolarization activated cyclic nucleotide gated potassium channel 1)
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    Models   Description
1.  A detailed Purkinje cell model (Masoli et al 2015)
The Purkinje cell is one of the most complex type of neuron in the central nervous system and is well known for its massive dendritic tree. The initiation of the action potential was theorized to be due to the high calcium channels presence in the dendritic tree but, in the last years, this idea was revised. In fact, the Axon Initial Segment, the first section of the axon was seen to be critical for the spontaneous generation of action potentials. The model reproduces the behaviours linked to the presence of this fundamental sections and the interplay with the other parts of the neuron.
2.  Alcohol excites Cerebellar Golgi Cells by inhibiting the Na+/K+ ATPase (Botta et al.2010)
Patch-clamp in cerebellar slices and computer modeling show that ethanol excites Golgi cells by inhibiting the Na+/K+ ATPase. In particular, voltage-clamp recordings of Na+/K+ ATPase currents indicated that ethanol partially inhibits this pump and this effect could be mimicked by low concentrations of the Na+/K+ ATPase blocker ouabain. The partial inhibition of Na+/K+ ATPase in a computer model of the Golgi cell reproduced these experimental findings that established a novel mechanism of action of ethanol on neural excitability.
3.  CA3 Network Model of Epileptic Activity (Sanjay et. al, 2015)
This computational study investigates how a CA3 neuronal network consisting of pyramidal cells, basket cells and OLM interneurons becomes epileptic when dendritic inhibition to pyramidal cells is impaired due to the dysfunction of OLM interneurons. After standardizing the baseline activity (theta-modulated gamma oscillations), systematic changes are made in the connectivities between the neurons, as a result of step-wise impairment of dendritic inhibition.
4.  Cerebellar cortex oscil. robustness from Golgi cell gap jncs (Simoes de Souza and De Schutter 2011)
" ... Previous one-dimensional network modeling of the cerebellar granular layer has been successfully linked with a range of cerebellar cortex oscillations observed in vivo. However, the recent discovery of gap junctions between Golgi cells (GoCs), which may cause oscillations by themselves, has raised the question of how gap-junction coupling affects GoC and granular-layer oscillations. To investigate this question, we developed a novel two-dimensional computational model of the GoC-granule cell (GC) circuit with and without gap junctions between GoCs. ..."
5.  Cerebellar Golgi cell (Solinas et al. 2007a, 2007b)
"... Our results suggest that a complex complement of ionic mechanisms is needed to fine-tune separate aspects of the neuronal response dynamics. Simulations also suggest that the Golgi cell may exploit these mechanisms to obtain a fine regulation of timing of incoming mossy fiber responses and granular layer circuit oscillation and bursting."
6.  Cerebellar purkinje cell: interacting Kv3 and Na currents influence firing (Akemann, Knopfel 2006)
Purkinje neurons spontaneously generate action potentials in the absence of synaptic drive and thereby exert a tonic, yet plastic, input to their target cells in the deep cerebellar nuclei. Purkinje neurons express two ionic currents with biophysical properties that are specialized for high-frequency firing: resurgent sodium currents and potassium currents mediated by Kv3.3. Numerical simulations indicated that Kv3.3 increases the spontaneous firing rate via cooperation with resurgent sodium currents. We conclude that the rate of spontaneous action potential firing of Purkinje neurons is controlled by the interaction of Kv3.3 potassium currents and resurgent sodium currents. See paper for more and details.
7.  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.
8.  Effect of voltage sensitive fluorescent proteins on neuronal excitability (Akemann et al. 2009)
"Fluorescent protein voltage sensors are recombinant proteins that are designed as genetically encoded cellular probes of membrane potential using mechanisms of voltage-dependent modulation of fluorescence. Several such proteins, including VSFP2.3 and VSFP3.1, were recently reported with reliable function in mammalian cells. ... Expression of these proteins in cell membranes is accompanied by additional dynamic membrane capacitance, ... We used recordings of sensing currents and fluorescence responses of VSFP2.3 and of VSFP3.1 to derive kinetic models of the voltage-dependent signaling of these proteins. Using computational neuron simulations, we quantitatively investigated the perturbing effects of sensing capacitance on the input/output relationship in two central neuron models, a cerebellar Purkinje and a layer 5 pyramidal neuron. ... ". The Purkinje cell model is included in ModelDB.
9.  Firing neocortical layer V pyramidal neuron (Reetz et al. 2014; Stadler et al. 2014)
Neocortical Layer V model with firing behaviour adjusted to in vitro observations. The model was used to investigate the effects of IFN and PKC on the excitability of neurons (Stadler et al 2014, Reetz et al. 2014). The model contains new channel simulations for HCN1, HCN2 and the big calcium dependent potassium channel BK.
10.  GC model (Beining et al 2017)
A companion modeldb entry (NEURON only) to modeldb accession number 231862.
11.  GP Neuron, somatic and dendritic phase response curves (Schultheiss et al. 2011)
Phase response analysis of a GP neuron model showing type I PRCs for somatic inputs and type II PRCs for dendritic excitation. Analysis of intrinsic currents underlying type II dendritic PRCs.
12.  Ih tunes oscillations in an In Silico CA3 model (Neymotin et al. 2013)
" ... We investigated oscillatory control using a multiscale computer model of hippocampal CA3, where each cell class (pyramidal, basket, and oriens-lacunosum moleculare cells), contained type-appropriate isoforms of Ih. Our model demonstrated that modulation of pyramidal and basket Ih allows tuning theta and gamma oscillation frequency and amplitude. Pyramidal Ih also controlled cross-frequency coupling (CFC) and allowed shifting gamma generation towards particular phases of the theta cycle, effected via Ih’s ability to set pyramidal excitability. ..."
13.  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. ..."
14.  Mature and young adult-born dentate granule cell models (T2N interface) (Beining et al. 2017)
... Here, we present T2N, a powerful interface to control NEURON with Matlab and TREES toolbox, which supports generating models stable over a broad range of reconstructed and synthetic morphologies. We illustrate this for a novel, highly-detailed active model of dentate granule cells (GCs) replicating a wide palette of experiments from various labs. By implementing known differences in ion channel composition and morphology, our model reproduces data from mouse or rat, mature or adult-born GCs as well as pharmacological interventions and epileptic conditions. ... T2N is suitable for creating robust models useful for large-scale networks that could lead to novel predictions. ..." See modeldb accession number 231818 for NEURON only code.
15.  Multitarget pharmacology for Dystonia in M1 (Neymotin et al 2016)
" ... We developed a multiscale model of primary motor cortex, ranging from molecular, up to cellular, and network levels, containing 1715 compartmental model neurons with multiple ion channels and intracellular molecular dynamics. We wired the model based on electrophysiological data obtained from mouse motor cortex circuit mapping experiments. We used the model to reproduce patterns of heightened activity seen in dystonia by applying independent random variations in parameters to identify pathological parameter sets. ..."
16.  Na+ channel dependence of AP initiation in cortical pyramidal neuron (Kole et al. 2008)
In this simulation action potential initiation, action potential properties and the role of axon initial segment Na+ channels are investigated in a realistic model of a layer 5 pyramidal neuron axon initial segment. The main Na+ channel properties were constrained by experimental data and the axon initial segment was reconstructed. Model parameters were constrained by direct recordings at the axon initial segment.
17.  Role of Ih in firing patterns of cold thermoreceptors (Orio et al., 2012)
" ... Here we investigated the role of Ih in cold-sensitive (CS) nerve endings, where cold sensory transduction actually takes place. Corneal CS nerve endings in mice show a rhythmic spiking activity at neutral skin temperature that switches to bursting mode when the temperature is lowered. ... Mathematical modeling shows that the firing phenotype of CS nerve endings from HCN1-/- mice can be reproduced by replacing HCN1 channels with the slower HCN2 channels rather than by abolishing Ih. We propose that Ih carried by HCN1 channels helps tune the frequency of the oscillation and the length of bursts underlying regular spiking in cold thermoreceptors, having important implications for neural coding of cold sensation. "
18.  Schiz.-linked gene effects on intrinsic single-neuron excitability (Maki-Marttunen et al. 2016)
Python scripts for running NEURON simulations that model a layer V pyramidal cell with certain genetic variants implemented. The genes included are obtained from genome-wide association studies of schizophrenia.
19.  SCZ-associated variant effects on L5 pyr cell NN activity and delta osc. (Maki-Marttunen et al 2018)
" … Here, using computational modeling, we show that a common biomarker of schizophrenia, namely, an increase in delta-oscillation power, may be a direct consequence of altered expression or kinetics of voltage-gated ion channels or calcium transporters. Our model of a circuit of layer V pyramidal cells highlights multiple types of schizophrenia-related variants that contribute to altered dynamics in the delta frequency band. Moreover, our model predicts that the same membrane mechanisms that increase the layer V pyramidal cell network gain and response to delta-frequency oscillations may also cause a decit in a single-cell correlate of the prepulse inhibition, which is a behavioral biomarker highly associated with schizophrenia."

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