NEURON source code for the model used in Reetz et al 2014 (Protein kinase C activation mediates interferon-beta-induced neuronal excitability changes in neocortical pyramidal neurons; Journal of Neuroinflammation doi: 10.1186/s12974-014-0185-4 http://www.ncbi.nlm.nih.gov/pubmed/25359459).
The HCN1 and HCN2 models were also used in Stadler et al. 2012 (Elevation in type I interferons inhibits HCN1 and slows cortical neuronal oscillations. Cerebral Cortex. doi:10.1093/cercor/bhs305)
Type I Interferons (IFNs) elevate the excitability of neocortical pyramidal neurons by attenuating the rheobase and increasing the F/I gain. The modulation of multiple ion channels underlies the effect, however, which channels are involved and how the interferon signalling cascade is linked to these channels is unknown.
We use an in silico model of a neocortical layer 5 neuron to test multiple single and combined current modulation which potentially could account for the change in firing behaviour.
The amount and type of modulation necessary to replicate the interferon effects suggests the activation of PKC as the main link between the ion channels and the type I IFN signalling cascade.
mosinit.hoc
Initialises and starts the model, see Usage below
LayerVrun.hoc
Main hoc to initialize the model, calls LayerVinit.hoc
LayerVinit.hoc
Assign general and channel parameters for the Layer V neuron
./sub/OwnInit.hoc
Replaces the standard init routine
./sub/ReducExp.hoc
Experiments with reduced current densities/properties
./sub/util.hoc
Several function to work with LayerVrun
./geo/Ri18geo.hoc
Geometry
various mod files for channel descriptions
MS Windows 7, NEURON 7.1 and 7.3 (64bit, other versions have not been tested)
When the folder is compiled using the mknrndll script the simulation can be started with "mosinit.hoc" (reproduces the data underlying Fig 1B - only some selected traces are shown there).
NB: This will take about two hours on a Intel i7-860
The calculated volatage traces and FI curves are saved in:
CCctrl.txt
first row: format of the saved matrix
first column of the matrix: time vector (ms), the remaining columns are the voltage traces (mV)
CCpkc.txt
same format as above
CCctrl_AP.txt (number for AP for every current step)
CCpkc_AP.txt (number for AP for every current step)
To just init the model call "LayerVrun.hoc", then:
see "util.hoc" for how to start a CCIV
see "ReducExp.hoc" for how to reduce current densities To reproduce fig 1C presented in the paper change the conductances here as stated in the article.
The geometry of the model is based on Stuart and Spruston 1998 (http://senselab.med.yale.edu/modeldb/ShowModel.asp?model=3677, Ri18). To facilitate access to the different sections, these were cumulated in
SectionList Axon: the axon
SectionList SomaDend: everything except the axon
SectionList Soma: the Soma
SectionList ApikalDend: apical dendrite
Array ApikalTrunk: trunk part of the apical dendrite
Default accessed section: dend1[21] (that's the middle of the soma)
| Author: | Konstantin Stadler |
| Version: | 20140217 |