Description

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)

Background

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.

Content

System

MS Windows 7, NEURON 7.1 and 7.3 (64bit, other versions have not been tested)

Usage

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:

To just init the model call "LayerVrun.hoc", then:

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

Default accessed section: dend1[21] (that's the middle of the soma)


Author: Konstantin Stadler
Version: 20140217