A structurally precise mechanism links an epilepsy-associated KCNC2 potassium channel mutation to interneuron dysfunction

PNAS paper link forthcoming

Results

Main

Supplementary

Getting started

Install Python (preferably using anaconda)
Create a virtual environment and install packages from environment.yml

conda env create -f environment.yml
Install additional python packages (NEURON and nrnutils)

pip install -r requirements.txt
(Alternative, Windows only) Install NEURON with an installer
Run notebook

jupyter lab notebook.ipynb or jupyter notebook notebook.ipynb

About

This model uses the NEURON simulation environment

HOC template for PV model is found in src/cells/PV_template.hoc

Morphology and mechanisms found under src/cells/morphologies and src/cells/mechanisms

Model morphology and mechanisms taken from the BBP Neocortical Microcircuit Portal: https://bbp.epfl.ch/nmc-portal/welcome

Original PV neuron derived from Berecki G, Bryson A, Terhag J, Maljevic S, Gazina EV, Hill SL, Petrou S (2019) SCN1A gain of function in early infantile encephalopathy. Ann Neurol 85:514-525 doi: 10.1002/ana.25438

The model was optimised using BluePyOpt:

"Van Geit W, Gevaert M, Chindemi G, Rossert C, Courcol J, Muller EB, Schurmann F, Segev I and Markram H (2016).BluePyOpt: Leveraging open source software and cloud infrastructure to optimise model parameters in neuroscience. Front. Neuroinform. 10:17. doi: 10.3389/fninf.2016.00017

The axon and sodium channels were adjusted for the paper: Developmentally-regulated impairment of parvalbumin interneuron synaptic transmission in an experimental model of Dravet syndrome