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

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Accession:223955
Model of pyramidal neurons that either hyper or hypo excitable due to SCN2A mutations. Mutations are taken from patients with ASD or Epilepsy
Reference:
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]
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:
Receptor(s):
Gene(s): Nav1.2 SCN2A;
Transmitter(s):
Simulation Environment: NEURON; MATLAB;
Model Concept(s): Epilepsy; Autism spectrum disorder;
Implementer(s): Ben-Shalom, Roy [bens.roy at gmail.com];
Search NeuronDB for information about:  Neocortex L5/6 pyramidal GLU cell; I Na,t; I K; I Sodium;
clear all
close all

GFactors = 1:-0.1:0;
namps = 0.5:0.05:3;
nampsEp = 0:0.05:3;
NRuns = length(namps)*length(GFactors);
minVForAP = -10;
dvdtThresh = 38;
dt=0.01;
load('KColormap.mat');
FNSoma = '.\YoungOrig\Volts.csv';
somaVolts = csvread(FNSoma,1,0);
somaVolts = reshape(somaVolts(:,1:length(namps)*length(GFactors)),10001,length(namps),length(GFactors));

FNSoma = '.\YoungD82G\Volts.csv';
somaVoltsD82G = csvread(FNSoma,1,0);
somaVoltsD82G = somaVoltsD82G(:,1:length(namps));


FNSoma = '.\YoungD82GRed\Volts.csv';
somaVoltsD82GRed = csvread(FNSoma,1,0);
somaVoltsD82GRed = somaVoltsD82GRed(:,1:length(namps));

FNSoma = '.\YoungD12N\Volts.csv';
somaVoltsD12N = csvread(FNSoma,1,0);
somaVoltsD12N = somaVoltsD12N(:,1:length(namps));



FNSoma = '.\YoungT1420MRed\Volts.csv';
somaVoltsT1420MRed = csvread(FNSoma,1,0);
somaVoltsT1420MRed = somaVoltsT1420MRed(:,1:length(namps));

FNSoma = '.\YoungL1536V\Volts.csv';
somaVoltsL1536V = csvread(FNSoma,1,0);
somaVoltsL1536V = somaVoltsL1536V(:,1:length(namps));

FNSoma = '.\YoungL1330F\Volts.csv';
somaVoltsL1330F = csvread(FNSoma,1,0);
somaVoltsL1330F = somaVoltsL1330F(:,1:length(namps));

FNSoma = '.\YoungI1473M\Volts.csv';
somaVoltsI1473M = csvread(FNSoma,1,0);
somaVoltsI1473M = somaVoltsI1473M(:,1:length(nampsEp));


FNSoma = '.\YoungE1211K\Volts.csv';
somaVoltsE1211K = csvread(FNSoma,1,0);
somaVoltsE1211K = somaVoltsE1211K(:,1:length(nampsEp));

%%
%stimInd = find(namps ==2.45);

%close all


maxAtSoma = zeros(length(namps),length(GFactors));
for gs = 1:length(GFactors)
    for i = 1:length(namps)
        maxAtSoma(i,gs) = max(somaVolts(:,i,gs));
        dvdtSoma = diff(somaVolts(2:end,i,gs))./dt;
        indOfThreshSoma = find(dvdtSoma>dvdtThresh,1,'first');
        if(~isempty(indOfThreshSoma))
            threshAtSoma(i,gs) = somaVolts(indOfThreshSoma,i,gs);
        end
    end
end
Ind1 = find(namps == 1.2);
dvdtsomaHet = diff(somaVolts(2:end,15,length(GFactors)-1))./dt;

threshAtSoma = [zeros(10,11); threshAtSoma];
figure(12331)


maxAtSomaD82G = zeros(length(namps),1);
threshAtSomaD82G = zeros(length(namps),1);

maxAtSomaD82GRed = zeros(length(namps),1);
threshAtSomaD82GRed = zeros(length(namps),1);

maxAtSomaD12N = zeros(length(namps),1);
threshAtSomaD12N = zeros(length(namps),1);

maxAtSomaT1420MRed = zeros(length(namps),1);
threshAtSomaT1420MRed = zeros(length(namps),1);

maxAtSomaL1536V = zeros(length(namps),1);
threshAtSomaL1536V = zeros(length(namps),1);

maxAtSomaL1330F = zeros(length(namps),1);
threshAtSomaL1330F = zeros(length(namps),1);

maxAtSomaI1473M = zeros(length(nampsEp),1);
threshAtSomaI1473M = zeros(length(nampsEp),1);

maxAtSomaE1211K = zeros(length(nampsEp),1);
threshAtSomaE1211K = zeros(length(nampsEp),1);

for i = 1:length(namps)
    
    maxAtSomaD82G(i) = max(somaVoltsD82G(:,i));
    dvdtD82G = diff(somaVoltsD82G(2:end,i))./dt;
    indOfThreshD82G = find(dvdtD82G>dvdtThresh,1,'first');
    if(~isempty(indOfThreshD82G))
        threshAtSomaD82G(i) = somaVoltsD82G(indOfThreshD82G,i);
    end
    maxAtSomaD82GRed(i) = max(somaVoltsD82GRed(:,i));
    dvdtD82GRed = diff(somaVoltsD82GRed(2:end,i))./dt;
    indOfThreshD82GRed = find(dvdtD82GRed>dvdtThresh,1,'first');
    if(~isempty(indOfThreshD82GRed))
        threshAtSomaD82GRed(i) = somaVoltsD82GRed(indOfThreshD82GRed,i);
    end
    maxAtSomaD12N(i) = max(somaVoltsD12N(:,i));
    dvdtD12N = diff(somaVoltsD12N(2:end,i))./dt;
    indOfThreshD12N = find(dvdtD12N>dvdtThresh,1,'first');
    if(~isempty(indOfThreshD12N))
        threshAtSomaD12N(i) = somaVoltsD12N(indOfThreshD12N,i);
    end
   
    maxAtSomaT1420MRed(i) = max(somaVoltsT1420MRed(:,i));
    dvdtT1420MRed = diff(somaVoltsT1420MRed(2:end,i))./dt;
    indOfThreshT1420MRed = find(dvdtT1420MRed>dvdtThresh,1,'first');
    if(~isempty(indOfThreshT1420MRed))
        threshAtSomaT1420MRed(i) = somaVoltsT1420MRed(indOfThreshT1420MRed,i);
    end
   
    maxAtSomaL1536V(i) = max(somaVoltsL1536V(:,i));
    dvdtL1536V = diff(somaVoltsL1536V(2:end,i))./dt;
    indOfThreshL1536V = find(dvdtL1536V>dvdtThresh,1,'first');
    if(~isempty(indOfThreshL1536V))
        threshAtSomaL1536V(i) = somaVoltsL1536V(indOfThreshL1536V,i);
    end
end
threshAtSomaT1420MRed = [zeros(10,1); threshAtSomaT1420MRed];
threshAtSomaD82G = [zeros(10,1); threshAtSomaD82G];
threshAtSomaD82GRed = [zeros(10,1); threshAtSomaD82GRed];
threshAtSomaD12N = [zeros(10,1); threshAtSomaD12N];
threshAtSomaL1536V = [zeros(10,1); threshAtSomaL1536V];



for i = 1:length(nampsEp)
    maxAtSomaI1473M(i) = max(somaVoltsI1473M(:,i));
    dvdtI1473M = diff(somaVoltsI1473M(100:end,i))./dt;
    indOfThreshI1473M = find(dvdtI1473M>dvdtThresh,1,'first');
    if(~isempty(indOfThreshI1473M))
        threshAtSomaI1473M(i) = somaVoltsI1473M(indOfThreshI1473M,i);
    end
    maxAtSomaE1211K(i) = max(somaVoltsE1211K(:,i));
    dvdtE1211K = diff(somaVoltsE1211K(100:end,i))./dt;
    indOfThreshE1211K = find(dvdtE1211K>dvdtThresh,1,'first');
    if(~isempty(indOfThreshE1211K))
        threshAtSomaE1211K(i) = somaVoltsE1211K(indOfThreshE1211K,i);
    end
end




Ind2 = find(namps == 2.2);
Ind1 = find(namps == 1.2);
Ind2Epi = find(nampsEp == 2.2);
ForIgorVoltsFull = somaVolts(:,[Ind2],1);
ForIgorVoltsHalf = somaVolts(:,[Ind2],end);
ForIgorTraces = [ForIgorVoltsFull,ForIgorVoltsHalf,somaVoltsD82G(:,Ind2),somaVoltsD82GRed(:,Ind2),somaVoltsD12N(:,Ind2),somaVoltsT1420MRed(:,Ind2),somaVoltsL1536V(:,Ind2),somaVoltsI1473M(:,Ind2Epi),somaVoltsE1211K(:,Ind2Epi),somaVoltsL1330F(:,Ind2Epi)];
fullSomaNaps = apsInds(somaVolts(:,:,end),-10);
HalfSomaNaps = apsInds(somaVolts(:,:,1),-10);



%forigorRehobase = [namps',fullSomaNaps(1:length(namps))',HalfSomaNaps(1:length(namps))',D82GShiftedNaps(1:length(namps))',D82GRedShiftedNaps(1:length(namps))',T1420MNaps(1:length(namps))',D12NNaps(1:length(namps))'];

 WTFull = somaVolts(:,:,1);
 WTNAps = apsInds(WTFull,-10);
 WTHalf = somaVolts(:,:,end);
 WTHalfNAps = apsInds(WTHalf,-10);
 D82GNAps = apsInds(somaVoltsD82G,-10);
 D82GRedNAps = apsInds(somaVoltsD82GRed,-10);
 D12NNAps = apsInds(somaVoltsD12N,-10);
T1420MRedNAps = apsInds(somaVoltsT1420MRed,-10);
L1536VNAps = apsInds(somaVoltsL1536V,-10);
I1473MNAps = apsInds(somaVoltsI1473M,-10);
E1211KNAps = apsInds(somaVoltsE1211K,-10);
L1330FNAps = apsInds(somaVoltsL1330F,-10);

% T1420MNAps = apsInds(somaVoltsT1420M,-10);
forIgorIO = [namps',WTNAps',WTHalfNAps',D82GNAps',D82GRedNAps',D12NNAps',T1420MRedNAps',L1536VNAps'];
%close all
mutantTitles = {'D82G','D82GRed','D12N','T1420MRed','L1536V','L1330F'};


figure(10)
hold on
plot(namps,WTNAps,'black');
plot(namps,WTHalfNAps,'red');
plot(namps,D82GNAps,'blue');
plot(namps,D82GRedNAps,'--blue');
plot(namps,D12NNAps,'green');
%plot(namps,T1420MNAps,'Magenta');
plot(namps,T1420MRedNAps,'Magenta');
plot(namps,L1330FNAps,'Cyan');

plot(namps,L1536VNAps,'Yellow');
plot(nampsEp,I1473MNAps,'Color',[0.5,0.5,0.5]);
plot(nampsEp,E1211KNAps,'Color',[0.8,0.8,0.8]);

title('# Spikes')


figure(102)
colormap jet;
imagesc(-1*GFactors,-1*nampsEp,threshAtSoma);

hold on
caxis([-67,-47]);
colormap(flipud(colormap));
colormap(gcf,kcolormap);
ylabel('Stimulation[nA]');
xlabel('Ratio of Nav1.2 at AIS');
title('Threshold at the soma');
colorbar;


mutantThreshAtSoma = [threshAtSomaD82G,threshAtSomaD82GRed,threshAtSomaD12N,threshAtSomaT1420MRed,threshAtSomaL1536V,threshAtSomaL1330F];
figure(112)
colormap jet;
imagesc(1:length(mutantTitles),-1*nampsEp,mutantThreshAtSoma);
ax =gca;
ax.XTickLabel = mutantTitles;
hold on
caxis([-67,-47]);
colormap(flipud(colormap));
colormap(gcf,kcolormap);
ylabel('Stimulation[nA]');
xlabel('Ratio of Nav1.2 at AIS');
title('Threshold at the soma Mutant');
ax = gca;
set(ax,'XTick',1:length(mutantTitles));
set(ax,'XTickLabel',mutantTitles);

colorbar;

figure(212)
colormap jet;
imagesc([1,2],-1*nampsEp,[threshAtSomaI1473M,threshAtSomaE1211K]);
ax =gca;
ax.XTickLabel = ['I1473M','E1211K'];
hold on
caxis([-76,-67]);
colormap(flipud(colormap));
colormap(gcf,kcolormap);
ylabel('Stimulation[nA]');
title('Threshold at the soma Epilepsy');
ax = gca;
set(ax,'XTick',[1 2]);
set(ax,'XTickLabel',{'I1473M','E1211K'});

colorbar;




figure(103)
colormap jet;
imagesc(-1*GFactors,-1*namps,maxAtSoma);

hold on
caxis([10,25]);
%caxis([-64,-48]);

ylabel('Stimulation[nA]');
xlabel('Ratio of Nav1.2 at AIS');
title('Max at the soma');
colorbar;


mutantMaxAtSoma = [maxAtSomaD82G,maxAtSomaD82GRed,maxAtSomaD12N,maxAtSomaT1420MRed,maxAtSomaL1536V,maxAtSomaL1330F];
figure(113)
colormap jet;
imagesc(1:length(mutantTitles),-1*namps,mutantMaxAtSoma);
ax = gca;
set(ax,'XTick',1:length(mutantTitles));
set(ax,'XTickLabel',mutantTitles);

hold on
caxis([10,25]);
%caxis([-64,-48]);

ylabel('Stimulation[nA]');
xlabel('Ratio of Nav1.2 at AIS');
title('Max at the soma Mutant');
colorbar;

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