Inhibitory network bistability explains increased activity prior to seizure onset (Rich et al 2020)

 Download zip file 
Help downloading and running models
Accession:266435
" ... the mechanisms predisposing an inhibitory network toward increased activity, specifically prior to ictogenesis, without a permanent change to inputs to the system remain unknown. We address this question by comparing simulated inhibitory networks containing control interneurons and networks containing hyperexcitable interneurons modeled to mimic treatment with 4-Aminopyridine (4-AP), an agent commonly used to model seizures in vivo and in vitro. Our in silico study demonstrates that model inhibitory networks with 4-AP interneurons are more prone than their control counterparts to exist in a bistable state in which asynchronously firing networks can abruptly transition into synchrony driven by a brief perturbation. This transition into synchrony brings about a corresponding increase in overall firing rate. We further show that perturbations driving this transition could arise in vivo from background excitatory synaptic activity in the cortex. Thus, we propose that bistability explains the increase in interneuron activity observed experimentally prior to seizure via a transition from incoherent to coherent dynamics. Moreover, bistability explains why inhibitory networks containing hyperexcitable interneurons are more vulnerable to this change in dynamics, and how such networks can undergo a transition without a permanent change in the drive. ..."
Reference:
1 . Rich S, Chameh HM, Rafiee M, Ferguson K, Skinner FK, Valiante TA (2020) Inhibitory Network Bistability Explains Increased Interneuronal Activity Prior to Seizure Onset. Front Neural Circuits 13:81 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Synapse;
Brain Region(s)/Organism:
Cell Type(s): Abstract Izhikevich neuron;
Channel(s): I Potassium;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s): Gaba;
Simulation Environment: C or C++ program;
Model Concept(s): Synchronization; Epilepsy;
Implementer(s): Rich, Scott [sbrich at umich.edu];
Search NeuronDB for information about:  I Potassium; Gaba;
/
CorticalInhibitoryNetwork-master
README.md
columnlegend.m
conv_gaussian.m
convert_spiketimes.m
getpos.m
golomb_measure.m
golomb_synch.m
InhibitoryCortex_pulse_0713.m
InhibitoryCortex_pulse_2d_FullWithRep_0905.m
InhibitoryCortex_pulse_bistabilitymeasure_zoom_repetitions_0823.m
InhibitoryCortex_pulse_stitchtogether_0709.m
InhibitoryCortex_pulse_stitchtogether_full_repetitions_0822.m
InhibitoryCortex_pulse_stitchtogether_zoom_0726.m
InhibitoryCortex_pulse_stitchtogether_zoom_repetitions_0813.m
InhibitoryCortex_pulse_zoom_0726.m
InhibitoryNetwork_cortex.sh
InhibitoryNetwork_cortex_0712.c
InhibitoryNetwork_cortex_IF_0615.c
InhibitoryNetwork_cortex_submit_0812.sh
InhibitoryNetwork_cortex_submit_zoom_0725.sh
InhibitoryNetwork_SortedRaster.m
legendflex.m
legendtitle.m
LICENSE *
mtit.m
parseArgs.m *
PlottingFICurves_v1.m
savemultfigs.m
subaxis.m *
suplabel.m
                            
clear
clc
close all

numsims=10;
numfull=5;
branges=cell(1, numsims/numfull);
bstart=2691;
bstartcsv=bstart;
for i=1:numsims/numfull
    branges{i}=bstart+(i-1)*numfull:(bstart+numfull-1)+(i-1)*numfull;
end
close all

for i=1:numsims/numfull
    brange=branges{i};
    
    %% File names
    load('progress_postpulse_2691to2700.mat');
    load('progress_prepulse_2691to2700.mat');
    
    %% Parameters
    numcells=500;
    endtime=2000;
    pulsetime=1000;
    dt=.01;
    steps=endtime/dt+1;
    
    % brange=106:105;
    
    numgsyn=20;
    numI=37;
    loopnum=numgsyn*numI;
    
    %% Construct Full Parameter Regime From Smaller Runs
    Synchrony_full=zeros(numI+1, numgsyn+1);
    popfreq_full=zeros(numI+1, numgsyn+1);
    
    count=1;
    for b=brange
        temp=csvread(csvname{1+b-bstartcsv,1});
        for k=1:(length(temp)/numI)
            Synchrony_full(1:numI, count)=temp((1+(k-1)*numI):(k*numI));
            count=count+1;
        end
    end
    
    count=1;
    for b=brange
        temp2=csvread(csvname{1+b-bstartcsv,2});
        for k=1:(length(temp2)/numI)
            popfreq_full(1:numI, count)=temp2((1+(k-1)*numI):(k*numI));
            count=count+1;
        end
    end
    
    %% Input data from csv files
    b=brange(1);
    
    current=cd;
    cd('/Users/scottrich/OneDrive - UHN/1) Compute Canada Files');
%             cd('E:\OneDrive - UHN\1) Compute Canada Files');
    
    str1=sprintf('InhibitoryNetwork_%d_TrackVariables.csv', b);
    str2=sprintf('InhibitoryNetwork_%d_SpikeTimes.csv', b);
    str3=sprintf('InhibitoryNetwork_%d_InputCurrents.csv', b);
    str4=sprintf('InhibitoryNetwork_%d_ConnectivityMatricies.csv', b);
    str5=sprintf('InhibitoryNetwork_%d_Parameters.csv', b);
    
    % trackvariables=csvread(str1);
    % spikes=csvread(str2);
    % currents=csvread(str3);
    % connectivity=csvread(str4);
    variables=csvread(str5);
    
    cd(current);
    
    
    csvname4=sprintf('Synchrony_postpulse_full_state%d_probii%1.0f_std%1.0f_num%dto%d.csv', variables(1,5), variables(1,1)*100, variables(1,4), brange(1),brange(end));
    csvname3=sprintf('PopulationFreq_postpulse_full_state%d_probii%1.0f_std%1.0f_num%dto%d.csv', variables(1,5), variables(1,1)*100, variables(1,4), brange(1),brange(end));
    csvwrite(csvname4,Synchrony_full);
    csvwrite(csvname3,popfreq_full);
    
    %% Plot Full Parameter Regime
    figure('units','normalized','position',[0 0 1 1])
    colormap jet
    
    subaxis(1,2,1, 'Spacing', 0.01, 'Padding', 0.05, 'Margin', 0.05, 'PaddingBottom', 0.12, 'PaddingTop', 0.075, 'PaddingLeft', 0.07, 'PaddingRight', 0.01);
    pcolor(Synchrony_full)
    caxis([0 1])
    colorbar
    
    xlabels=0.25:.5:5;
    ylabels=100:100:1000;
    
    set(gca,'TickDir','out')
    set(gca,'box','off')
    set(gca, 'XTick', 1.5:2:20.5);
    set(gca, 'XTickLabel', xlabels);
    set(gca, 'YTick', 1.5:4:37.5);
    set(gca, 'YTickLabel', ylabels);
    xtickangle(45)
    ytickangle(45)
    set(gca, 'FontSize', 20);
    % ylabel({'Inter-connectivity Density'; 'Compared to E-E Density'}, 'FontSize', 26)
    % xlabel('Inhibitory Synaptic Weight (nS)', 'FontSize', 26)
    ylabel('External Applied Current (pA)', 'FontSize', 26)
    title('Synchrony Measure', 'FontSize', 30);
    
    subaxis(1,2,2, 'Spacing', 0.01, 'Padding', 0.05, 'Margin', 0.05, 'PaddingBottom', 0.12, 'PaddingTop', 0.075, 'PaddingRight', 0.01, 'PaddingLeft', 0.05);
    pcolor(popfreq_full)
    caxis([0 200])
    colorbar
    
    set(gca,'TickDir','out')
    set(gca,'box','off')
    set(gca, 'XTick', 1.5:2:20.5);
    set(gca, 'XTickLabel', xlabels);
    set(gca, 'YTick', []);
    set(gca, 'YTickLabel', ylabels);
    xtickangle(45)
    ytickangle(45)
    set(gca, 'FontSize', 20);
    % ylabel({'Inter-connectivity Density'; 'Compared to E-E Density'}, 'FontSize', 26)
    % xlabel('Inhibitory Synaptic Weight (nS)', 'FontSize', 26)
    % ylabel('External Applied Current (pA)', 'FontSize', 26)
    title('Mean Firing Frequency (Hz)', 'FontSize', 30);
    
    supAxis=[.0750 .10 .85 .85];
    str1= sprintf('Inhibitory Synaptic Weight (nS)');
    str3= sprintf('Connectivity Density: %1.2f; State: %1.0f; Post-Pulse', variables(1,1), variables(1,5));
    [ax,h]=suplabel(str1, 'x', supAxis);
    set(h, 'FontSize', 26);
    [ax3,h3]=suplabel(str3, 't', supAxis);
    set(h3, 'FontSize', 20);
    
    
    
    str1=sprintf('FullRange_postpulse_state%d_probii%1.0f_std%1.0f_num%dto%d.png', variables(1,5), variables(1,1)*100, variables(1,4), brange(1),brange(end));
    %     saveas(gcf, str1)
    set(gcf,'PaperPositionMode','auto')
    print(str1, '-dpng', '-r0');
    
    %% Construct Full Parameter Regime From Smaller Runs PRE PULSE
    Synchrony_full=zeros(numI+1, numgsyn+1);
    popfreq_full=zeros(numI+1, numgsyn+1);
    
    count=1;
    for b=brange
        temp=csvread(csvname2{1+b-bstartcsv,1});
        for k=1:(length(temp)/numI)
            Synchrony_full(1:numI, count)=temp((1+(k-1)*numI):(k*numI));
            count=count+1;
        end
    end
    
    count=1;
    for b=brange
        temp2=csvread(csvname2{1+b-bstartcsv,2});
        for k=1:(length(temp2)/numI)
            popfreq_full(1:numI, count)=temp2((1+(k-1)*numI):(k*numI));
            count=count+1;
        end
    end
    
    %% Input data from csv files
    b=brange(1);
    
    current=cd;
    cd('/Users/scottrich/OneDrive - UHN/1) Compute Canada Files');
%             cd('E:\OneDrive - UHN\1) Compute Canada Files');
    
    str1=sprintf('InhibitoryNetwork_%d_TrackVariables.csv', b);
    str2=sprintf('InhibitoryNetwork_%d_SpikeTimes.csv', b);
    str3=sprintf('InhibitoryNetwork_%d_InputCurrents.csv', b);
    str4=sprintf('InhibitoryNetwork_%d_ConnectivityMatricies.csv', b);
    str5=sprintf('InhibitoryNetwork_%d_Parameters.csv', b);
    
    % trackvariables=csvread(str1);
    % spikes=csvread(str2);
    % currents=csvread(str3);
    % connectivity=csvread(str4);
    variables=csvread(str5);
    
    cd(current);
    
    
    csvname4=sprintf('Synchrony_prepulse_full_state%d_probii%1.0f_std%1.0f_num%dto%d.csv', variables(1,5), variables(1,1)*100, variables(1,4), brange(1),brange(end));
    csvname3=sprintf('PopulationFreq_prepulse_full_state%d_probii%1.0f_std%1.0f_num%dto%d.csv', variables(1,5), variables(1,1)*100, variables(1,4), brange(1),brange(end));
    csvwrite(csvname4,Synchrony_full);
    csvwrite(csvname3,popfreq_full);
    
    %% Plot Full Parameter Regime
    figure('units','normalized','position',[0 0 1 1])
    colormap jet
    
    subaxis(1,2,1, 'Spacing', 0.01, 'Padding', 0.05, 'Margin', 0.05, 'PaddingBottom', 0.12, 'PaddingTop', 0.075, 'PaddingLeft', 0.07, 'PaddingRight', 0.01);
    pcolor(Synchrony_full)
    caxis([0 1])
    colorbar
    
    xlabels=0.25:.5:5;
    ylabels=100:100:1000;
    
    set(gca,'TickDir','out')
    set(gca,'box','off')
    set(gca, 'XTick', 1.5:2:20.5);
    set(gca, 'XTickLabel', xlabels);
    set(gca, 'YTick', 1.5:4:37.5);
    set(gca, 'YTickLabel', ylabels);
    xtickangle(45)
    ytickangle(45)
    set(gca, 'FontSize', 20);
    % ylabel({'Inter-connectivity Density'; 'Compared to E-E Density'}, 'FontSize', 26)
    % xlabel('Inhibitory Synaptic Weight (nS)', 'FontSize', 26)
    ylabel('External Applied Current (pA)', 'FontSize', 26)
    title('Synchrony Measure', 'FontSize', 30);
    
    subaxis(1,2,2, 'Spacing', 0.01, 'Padding', 0.05, 'Margin', 0.05, 'PaddingBottom', 0.12, 'PaddingTop', 0.075, 'PaddingRight', 0.01, 'PaddingLeft', 0.05);
    pcolor(popfreq_full)
    caxis([0 200])
    colorbar
    
    set(gca,'TickDir','out')
    set(gca,'box','off')
    set(gca, 'XTick', 1.5:2:20.5);
    set(gca, 'XTickLabel', xlabels);
    set(gca, 'YTick', []);
    set(gca, 'YTickLabel', ylabels);
    xtickangle(45)
    ytickangle(45)
    set(gca, 'FontSize', 20);
    % ylabel({'Inter-connectivity Density'; 'Compared to E-E Density'}, 'FontSize', 26)
    % xlabel('Inhibitory Synaptic Weight (nS)', 'FontSize', 26)
    % ylabel('External Applied Current (pA)', 'FontSize', 26)
    title('Mean Firing Frequency (Hz)', 'FontSize', 30);
    
    supAxis=[.0750 .10 .85 .85];
    str1= sprintf('Inhibitory Synaptic Weight (nS)');
    str3= sprintf('Connectivity Density: %1.2f; State: %1.0f; Pre-Pulse', variables(1,1), variables(1,5));
    [ax,h]=suplabel(str1, 'x', supAxis);
    set(h, 'FontSize', 26);
    [ax3,h3]=suplabel(str3, 't', supAxis);
    set(h3, 'FontSize', 20);
    
    
    
    str1=sprintf('FullRange_prepulse_state%d_probii%1.0f_std%1.0f_num%dto%d.png', variables(1,5), variables(1,1)*100, variables(1,4), brange(1),brange(end));
    %     saveas(gcf, str1)
    set(gcf,'PaperPositionMode','auto')
    print(str1, '-dpng', '-r0');
    
    
end

Loading data, please wait...