Hyperexcitability from Nav1.2 channel loss in neocortical pyramidal cells (Spratt et al 2021)

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Accession:267067
Based on the Layer 5 thick-tufted pyramidal cell from the Blue Brain Project, we modify the distribution of the sodium channel Nav1.2 to recapitulate an increase in excitability observed in ex vivo slice experiments.
Reference:
1 . Spratt PWE, Alexander RPD, Ben-Shalom R, Sahagun A, Kyoung H, Keeshen CM, Sanders SJ, Bender KJ (2021) Paradoxical hyperexcitability from NaV1.2 sodium channel loss in neocortical pyramidal cells Cell Rep. 36(5):109483 [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: Prefrontal cortex (PFC);
Cell Type(s): Neocortex layer 5 pyramidal cell;
Channel(s): I h; I M; I Potassium; I Sodium; I L high threshold; I T low threshold;
Gap Junctions:
Receptor(s):
Gene(s): Nav1.2 SCN2A;
Transmitter(s):
Simulation Environment: NEURON; Python;
Model Concept(s):
Implementer(s): Ben-Shalom, Roy [rbenshalom at ucdavis.edu]; Kyoung, Henry [hkyoung at berkeley.edu];
Search NeuronDB for information about:  I L high threshold; I T low threshold; I M; I h; I Sodium; I Potassium;
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SprattEtAl2021
Na12 Analysis
mechanisms
morphology
params
Stims
Volts
README *
axon_utils.hoc
biophysics.hoc *
cellinfo.json *
constants.hoc *
creategui.hoc *
createsimulation.hoc *
fit.hoc *
gui.ses *
init.hoc *
LICENSE *
morphology.hoc *
mosinit.hoc *
NaV12_analysis.ipynb *
ringplot.hoc *
run.py *
run_RmpRiTau.py *
runModel.hoc *
template.hoc *
topo_code.hoc *
                            
/*
Copyright (c) 2015 EPFL-BBP, All rights reserved.

THIS SOFTWARE IS PROVIDED BY THE BLUE BRAIN PROJECT ``AS IS''
AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO,
THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR
PURPOSE ARE DISCLAIMED. IN NO EVENT SHALL THE BLUE BRAIN PROJECT
BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR
CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF
SUBSTITUTE GOODS OR SERVICES; LOSS OF USE, DATA, OR PROFITS; OR
BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY,
WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT (INCLUDING NEGLIGENCE
OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE OF THIS SOFTWARE, EVEN
IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/legalcode or send a letter to Creative Commons, 171
Second Street, Suite 300, San Francisco, California, 94105, USA.
*/


/*                                                                               
 * @file creategui.hoc                                                           
 * @brief Draw the GUI                                
 * @author Werner Van Geit @ BBP                                                 
 * @date 2015                                                                    
*/        

load_file("ringplot.hoc")

pwmcnt = PWManager[0].count  // the initial GUIs should not be dismissed

objref mainhbox
objref plotvbox
objref shapehbox
objref synapsevbox
objref synapsevbox_size
objref gV, sP, rP, synapse_plot                                                               


xres = 1200
yres = 800
xstart = 50
ystart = 0

proc make_mainwindow() {
    mainhbox = new HBox(3)
    mainhbox.intercept(1)

    mainhbox.adjuster(200)
    make_runcontrol()

    mainhbox.adjuster(700)
    make_plottingpanel()

    mainhbox.adjuster(250)
    make_synapsepanel($o1)

    mainhbox.adjuster(250)
    mainhbox.intercept(0)   
    mainhbox.full_request(1) 
    mainhbox.map("Main", xstart, ystart, xres, yres)
}

proc make_plottingpanel() {
    plotvbox = new VBox()
    plotvbox.intercept(1)

    plotvbox.adjuster(300)
    make_shapepanel()
    
    plotvbox.adjuster(500)
    rP = new RingPlot()                                                         

    plotvbox.intercept(0)    
    mainhbox.full_request(1) 
    plotvbox.map("Plotting", 0, 0, -1, -1)
}


proc make_runcontrol() {                                                   
    xpanel("RunControl", 0)                                                     
    xbutton("Init & Run","restart()")                                           
    xbutton("Stop","stoprun=1")                                                 
    xvalue("Total time", "tstop")                                                 
    xvalue("Sim Time","t", 0,"", 0, 1 )                                 
    xvalue("Real Time","realtime", 0,"", 0, 1 )                                 
    xbutton("Quit","quit()")
    
    xlabel("Step current")
    xradiobutton("No step","stepcurrent=\"none\"", 1)                                                                                
    xradiobutton("Step current 1","stepcurrent=\"stepcurrent1\"")            
    xradiobutton("Step current 2","stepcurrent=\"stepcurrent2\"")               
    xradiobutton("Step current 3","stepcurrent=\"stepcurrent3\"")               
    xpanel(1498, 0)
} 
                                                                                
proc make_shapepanel() {                                                                                                                                                                                                     
    shapehbox = new HBox()
    shapehbox.intercept(1)

    shapehbox.adjuster(350)
    sP = new PlotShape(0)                                                       
    sP.variable("soma", "v(0.5)")                                               
    sP.view(-594.956, -98.0373, 1260.25, 1188.42, 573, 0, 505.92, 592)         
    sP.exec_menu("Shape Plot")                                                  

    shapehbox.adjuster(350)                                    
    synapse_plot = new Shape(0)
    synapse_plot.view(-594.956, -98.0373, 1260.25, 1188.42, 49, 0, 500.16, 592)
 
    shapehbox.intercept(0)    
    shapehbox.full_request(1) 
    plotvbox.full_request(1) 
    mainhbox.full_request(1) 
    shapehbox.map("Shapes", 1104, 0, -1, -1)                                                          
}                  

proc make_synapsepanel() { local n_of_pre_mtypes, pre_mtype_id localobj active_pre_mtypes, pre_mtype_freqs
    strdef pre_mtype_name

    synapsevbox = new HBox()
    synapsevbox.intercept(1)
    xpanel("Synapses")
    xlabel("Presyn m-types")
    for i=0, $o1.synapses.pre_mtypes.size-1 {
         pre_mtype_id = $o1.synapses.pre_mtypes.x[i]
         pre_mtype_freqs = $o1.synapses.pre_mtype_freqs
         pre_mtype_name = $o1.synapses.id_mtype_map.o(pre_mtype_id).s
         active_pre_mtypes = $o1.synapses.active_pre_mtypes
         xstatebutton(pre_mtype_name, &active_pre_mtypes.x[pre_mtype_id], "cell.synapses.update_synapses(synapse_plot)")
    }
    xpanel(100, 0)

    xpanel("Freq")
    xlabel("Frequency (Hz)")
    for i=0, $o1.synapses.pre_mtypes.size-1 {
         pre_mtype_id = $o1.synapses.pre_mtypes.x[i]
         pre_mtype_freqs = $o1.synapses.pre_mtype_freqs
         pre_mtype_name = $o1.synapses.id_mtype_map.o(pre_mtype_id).s
         active_pre_mtypes = $o1.synapses.active_pre_mtypes
         xpvalue("", &pre_mtype_freqs.x[pre_mtype_id], 0, "cell.synapses.update_synapses(synapse_plot)", 1)
    }
    xpanel(100, 0)

    synapsevbox.intercept(0)

    show_synapsepanel()
}

proc show_synapsepanel() {
    if (synapses_enabled == 1) {
        synapsevbox.map("Presynaptic activity", 0, 0, -1, -1)
    } else {
        synapsevbox.unmap()
    }
}