delvendahl/scn2a_simulations_hmg

Model from Asadollahi et al. Hum. Mol. Genet. 2023

Pyramidal neuron model for studying SCN2A mutations

This repository contains NEURON and Python files to simulate the effect of different SCN2A mutations in a reconstructed mouse cortical L5 pyramidal neuron. This model was used to study the effect of sodium channel mutations on the firing rate of a pyramidal neuron in the following publication (Asadollahi et al. 2023):

Asadollahi R., Delvendahl I., et al. (2023) Pathogenic SCN2A variants cause early-stage dysfunction in patient-derived neurons. Human Molecular Genetics, ddad048 (doi:10.1093/hmg/ddad048)

The model was constructed using the NEURON modeling language and is based on the implementation by Ben-Shalom et al. 2017 of the model that accompanied the paper "State and location dependence of action potential metabolic cost" (Hallermann et al. 2012).

Simulations were run with NEURON 8.0 in Python 3.8.12 (NEURON can be installed via pip install neuron). Python dependencies: neuron, numpy, scipy (run pip install -r requirements.txt)

To run simulations:

• compile all .mod files (cd to directory and execute nrnivmodl)
• in run_simulation.py, select which model to run by setting the name of the .hoc file to be loaded (from "/sim_files/" folder), e.g.:
  name_of_sim = 'youngPN'
• In the paper, the different simulation runs were the following:
  • WT (100% SCN2A): "youngPN"
  • 50% SCN2A: "youngPN_scn2a_ais_50perc"
  • 0% SCN2A: "youngPN_scn2a_ais_0perc"
  • E1803G: "youngPN_scn2a_ais_E1803G_het_2"
• adjust current injection amplitude and number of increasing sweeps, if desired:
  currentstep = 0.1
sweeps = 24
• run the file run_simulation.py
• the file run_simulation_MP.py can be used for running multiple simulations in parallel using multiprocessing
• the file plot_results.py can be used for plotting the results

The simulation output is saved as .txt files into the folder "Results/". Subfolders are created for each independent condition. Output files are:

• "spiking_results.txt" -> current injection, spike numbers, threshold, amplitude and spike delay, spikes AIS, threshold AIS, amplitude AIS, soma I_Na, AIS_I_Na
• "soma_AP_traces.txt" -> voltage traces of the soma
• "soma_Na_current.txt" -> Na current traces (from soma)
• "ais_Na_current.txt" -> Na current traces (from AIS)

---

Contact: [email protected]