Pyramidal neurons with mutated SCN2A gene (Nav1.2) (Ben-Shalom et al 2017)

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Model of pyramidal neurons that either hyper or hypo excitable due to SCN2A mutations. Mutations are taken from patients with ASD or Epilepsy
1 . Ben-Shalom R, Keeshen CM, Berrios KN, An JY, Sanders SJ, Bender KJ (2017) Opposing Effects on NaV1.2 Function Underlie Differences Between SCN2A Variants Observed in Individuals With Autism Spectrum Disorder or Infantile Seizures. Biol Psychiatry 82:224-232 [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism:
Cell Type(s): Neocortex L5/6 pyramidal GLU cell;
Channel(s): I Na,t; I Sodium; I K;
Gap Junctions:
Gene(s): Nav1.2 SCN2A;
Simulation Environment: NEURON; MATLAB;
Model Concept(s): Epilepsy; Autism spectrum disorder;
Implementer(s): Ben-Shalom, Roy [rbenshalom at];
Search NeuronDB for information about:  Neocortex L5/6 pyramidal GLU cell; I Na,t; I K; I Sodium;
readme.txt *
Cad.mod *
CaH.mod *
CaT.mod *
charge.mod *
h.mod *
Kca.mod *
Kv.mod *
Kv1_axonal.mod *
Kv7.mod *
na8st.mod *
na8st1.mod *
nax8st.mod *
28_04_10_num19.hoc *
Cell parameters.hoc *
charge.hoc *
mosinit.hoc *
scn2aExps.hoc *
This model reproduces Figure 6a and 6b and Supplementary Figure 5b of
the article

"State and location dependence of action potential metabolic cost in
cortical pyramidal neurons". Nature Neuroscience (2012)

When the folder is compiled using the mknrndll script the simulation
can be started with "mosinit.hoc".

The newly developed model of the axonal K+ currents (Kv1_axonal.mod)
was based on step evoked K+ currents including activation,
deactivation and inactivation protocols as well as steady state
curves. To describe the activation, eight Hodgkin-Huxley gates were
used (n^8). To describe the biphasic inactivation and recovery from
inactivation, two populations of channels with different
Hodgkin-Huxley inactivation gates were used (n^8*h1^+n^8*h2).

To analyze the AP efficiency and the ATP usage on a subcellular level,
the Na+/K+ charge overlap, the excess Na+ influx and the ATP usage
were calculated as RANGE variables (charge.mod).

Executing "ch()" in the terminal shell (see charge.hoc) will print
average ATP usage per cellular compartment as shown below (some of the
information is exported into text files).


The Na influx was analyzed from 517.000000 to 535.000000 ms
Required ATP molecules to pump Na ions out:
Total: 1.998503e+08
Soma: 1.416016e+07
Basal dendrite: 4.609883e+07
Apical dendrite: 9.149446e+07
Axon Initial Segment: 2.498228e+07
Axon collaterals: 2.095502e+07
Myelin: 7.227968e+05
Node: 1.436733e+06


Required ATP molecules to pump Na ions out per um^2:
Total: 2.818287e+03
Soma: 6.810007e+03
Basal dendrite: 2.531221e+03
Apical dendrite: 2.213969e+03
Axon Initial Segment: 5.531797e+04
Axon collaterals: 3.932075e+03
Myelin: 2.081271e+02
Node: 3.517895e+04
Total area (um^2): 7.091197e+04
Soma area (um^2): 2.079316e+03

For questions please contact or

June 12th 2012, Stefan Hallermann

20140226 ModelDB Administrator: To prevent collision with NEURON's
"charge" the "charge" mechanism has been changed to "charge_" with
changes in the hoc code.  The charge in names of files was left