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Na+ channel dependence of AP initiation in cortical pyramidal neuron (Kole et al. 2008)
Accession: 114394
In this simulation action potential initiation, action potential properties and the role of axon initial segment Na+ channels are investigated in a realistic model of a layer 5 pyramidal neuron axon initial segment. The main Na+ channel properties were constrained by experimental data and the axon initial segment was reconstructed. Model parameters were constrained by direct recordings at the axon initial segment.
Reference: Kole MH, Ilschner SU, Kampa BM, Williams SR, Ruben PC, Stuart GJ (2008) Action potential generation requires a high sodium channel density in the axon initial segment. Nat Neurosci 11:178-86 [PubMed]
Citations  Citation Browser
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):  Neocortical pyramidal neuron: deep;  
Channel(s):  I Na,t; I K; I M; I h;  
Gap Junctions:  
Receptor(s):  
Gene(s):  
Transmitter(s):  
Simulation Environment:  Neuron;
Model Concept(s):  Action Potential Initiation; Active Dendrites; Axonal Action Potentials; Action Potentials;
Implementer(s):  Kole, Maarten [m.kole at nin.knaw.nl];
Search NeuronDB for information about:  Neocortical pyramidal neuron: deep; I Na,t; I K; I M; I h;
Model files   Download zip file   Auto-launch             Help downloading and running models
\
NN_kole
readme.html
screenshot.jpg
screenshot_adjust.jpg
screenshot_morphology.jpg
Km.mod
kv.mod
Kv1.mod
na.mod
nax.mod
h.mod
A3+AIS_original.hoc
figure6a.hoc
mosinit.hoc
initiate_neuron.hoc
panels.ses
                            
26/07/2008 Maarten H.P.Kole

This model reproduces Figure 6a of the article 

"Action potential generation requires a high sodium channel density in
the axon initial segment". Nature Neuroscience 11(2):178-86
(2008). 
http://www.nature.com/neuro/journal/v11/n2/abs/nn2040.html

The example simulation shows that even with specific
voltage-dependence of axonal Na+ channels a channel density of
~50-fold higher is required for robust initiation in the AIS.

The voltage-dependence of activation and inactivation of the Na+
channels are constrained by the experimentally measured properties of
the somato-dendritic (SD) and axon initial segment (AIS) Na+
channels. These two populations are defined within the "na.mod" and
"nax.mod" files, respectively, and based on Hodgkin-Huxley
formalism. Details on the specific channel kinetics and properties can
be found in the Supplementary Information of the paper. The mod file
was obtained from Mainen and Sejnowski (1996).

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

For questions please contact maarten.kole@anu.edu.au

Example usage: auto-launch the simulation from ModelDB or download and
extract the archive and then under

linux/unix:
-----------
Compile the mod files by cd'ing to NN_kole and running nrnivmodl.
Start the simulation with
nrngui mosinit.hoc

MAC OS X:
---------
Drag and drop the NN_kole folder onto the mrknrndll icon.  Drag and
drop the mosinit.hoc file onto the nrngui icon.

Windows:
--------
Compile the mod files by starting mknrndll, changing directory to the 
NN_kole folder and selecting to make the nrnmech.dll.  Double click on the
mosinit.hoc file in a windows explorer window.

Once the simulation is started:
-------------------------------

The morphology of the cell

channel denisties

an instantaneous plot of the voltage as a function of distance
thoughout the cell, and other windows appear.

You can recreate figure 6a left from the publication by pressing Init & Run
in the RunControl Box.  

Select "Keep lines" in the voltage graph (drag from empty box
in the upper left corner and release mouse button on this menu item),
and, optionally, select to change the v(0.5) trace to a black dotted
line (use the Color/Brush menu item on the previous menu list, select
a black line and a dotted line and then click on the v(.5) text on the
graph).

Then changing the channel density by typing the new values into the
box:

channel denisties

and then press Init & Run again.  Repeat with the remaining value
(simulation starts with 3000 so you will have to run with 4000 and
2000.  When done the graph should look like:

channel denisties


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