% Created by Anatoly Yu. Buchin, August-Octorber, 2014
% Excitatory Bazhenov neuron
% Inhibitory Chow neurons
tic % start the timer
% SN border import
load('Ko_Cli.mat','Cli1','Cli2','Ko1','Ko2');
%% Parameters
T=200; % total time, mS
Tst=3000; % duration of stimulation, ms
dt=0.05; % time step, ms
Tframe=0; % first frame for the movie
dTframe=10;
frame=1;
% LFP model parameters
k=0.02; % prop. coefficient, 2*pi*a*p*R1^2/sigma/R/ri
% a - dendrite diameter
% p - density of charges (pyramidal cells)
% R1 - radius of a spheric layer
% sigma - average conductivity of an extracellular matrix
% R - distance of the electrode from the spherical layer
%
%% NETWORK ELEMETS
% Ne=9;
Ne=841; Ni=225;
% Ne=2500;
% Ne=8100;
%% BAZHENOV MODEL PARAMETERS
% Mg
Mg=1; % mM, Mg concentration for NMDA synapses
% CL
Clo=130; % mM
Vhalf=40; % KCC2 1/2
Ikcc2=2*ones(Ne,1); % KCC2 max current 0.5 norm, 0 path
HCO3o=26; % mM
HCO3i=16; % mM
kCL=100; % CL conversion factor, 1000 cm^3
% K
Ki_e=150; % intra K, mM
kK=10; % K conversion factor, 1000 cm^3
d=0.15; % ratio Volume/surface, m
D=4e-6; % diffusion coefficient, cm^2/s 4e-6, mum^2/ms = cm^2/s*10-8 [Bazhenov 2004]
dx=50*1e-4; % distance between volume centers, cm
% NA
Nao=130; % extra Na, mM
Nai=20; % intra Na, mM
kNa=10; % NA conversion, 1000 cm^3
% single cell and membrane parametersNe=8100; Ni=1936;
Cm=0.75; % mu F/cm^2
e0=26.6393; % kT/F, in Nernst equation
kappa=10000; % conductance between compartments, Ohm
S_Soma=0.000001; % cm^2
S_Dend=0.000165; % cm^2
% constants
F=96489; % coul/M
% somatic
G_Na=3450.0; % Na, mS/cm^2
G_Kv=200.0; % Kv-channel mS/cm^2
gg_kl=0.042; % K leak, mS/cm^2
gg_Nal=0.0198; % Na leak, mS/cm^2
Vbolz_E=22; % mV
% dendritic
G_NaD=1.1; % mS/cm^2
G_NapD=3.5; % mS/cm^2
G_HVA=0.0195; % mS/cm^2
G_kl=0.044; % K leak, mS/cm^2
G_lD=0.01; % Clleak, mS/cm^2
G_Nal=0.02; % Na leak, mS/cm^2
E_Ca=140; % mV
TauCa=800; % ms
DCa=0.85; % ???
G_KCa=2.5; % mS/cm^2
G_Km_E=0.01; % mS/cm^2
% Pump parametes and glial buffer
Koalpha=3.5; % mM
Naialpha=20; % mM
Imaxsoma=25; % muA/cm^2
Imaxdend=25; % muA/cm^2
Kothsoma=15; % mM
koff=0.0008; % 1/ mM / ms 0.0008 in Bazh model
K1n=1.0; % 1/ mM
Bmax=500; % mM
% SYNAPTIC CONNECTIONS
% AMPA
alpha2_AMPA=0.185;
tau_AMPA=1/alpha2_AMPA; % 5.4 ms
V_AMPA=0; % mV
A_E=1/dt; % delta-funciton appr, step increase for g_AMPA
% NMDA
tau_NMDA_rise=2; % ms
tau_NMDA_decay=100; % ms
alpha_NMDA=0.5; % 1/ms
V_NMDA=0; % mV
% GABA-A
alpha2_GABA=0.120;
tau_GABA=1/alpha2_GABA; % ms 8.33
V_GABA=-75; % mV
% refractory period, same for E and I pop
t_ref=2;
%% SYNAPTIC NOISE TO NEURONS
%{
% synaptic noise to E population
CE=0; % number of synapses per P neuron
SE_AMPA=0.5; % average value of synaptic gating variable
tauE_AMPA=1/alpha2_AMPA; %
gE_AMPA=0.001; % conductance per external input uS/cm^2
VE_av=-70; % numerical estimate of mean(VEnorm)
sigmaE=gE_AMPA*sqrt(CE*SE_AMPA*tauE_AMPA)*(VE_av-V_AMPA);
IE_AMPA=zeros(Ne,1);
%}
%% ICs EXC POP
% KCC2-PATHOLOGY
% Npath=randperm(Ne,round(0.05*Ne)); % RANDOM PATHOLOGY
% Npath=central_elements(sqrt(Ne),10); % PATHOLOGY IN A CENTRAL CLUSTER
Npath=[]; % NO PATHOLOGY
% Npath=450; % PATH in one neuron
% KCC2 NORM
Nnorm=1:1:Ne;
Nnorm(intersect(Npath,Nnorm))=[];
Ikcc2(Npath)=0; % PATHOLOGY
%Diffusion matrix
A_diff=M_diff(sqrt(Ne));
% Indexes of all connected elements
l=zeros(Ne,4);
for i=1:1:Ne
l(i,1:end)=find(A_diff(i,1:end)>0);
end
% random ICs KCC2(+)
Bs=random('normal',499.93,0,Ne,1); % mM buffer sould not be random
Cli=subplus(random('normal',3.46,0,Ne,1)); % mM 5.13, Ikcc2=0.5
Ko=subplus(random('normal',3.35,0,Ne,1)); % mM 3.25
cai=subplus(random('normal',0,0,Ne,1)); % mM
VD=random('normal',-70.04,0,Ne,1); % mV
VSOMA=random('normal',-70.09,0,Ne,1); % mV
m_iKv=subplus(random('normal',0.00,0,Ne,1)); % 1
m_iNa=subplus(random('normal',0.01,0,Ne,1)); % 1
h_iNa=subplus(random('normal',0.91,0,Ne,1)); % 1
m_iNaD=subplus(random('normal',0.00,0,Ne,1)); % 1
h_iNaD=subplus(random('normal',0.91,0,Ne,1)); % 1
m_iNapD=subplus(random('normal',0.00,0,Ne,1)); % 1
m_iKCa=subplus(random('normal',0.00,0,Ne,1)); % 1
m_iHVA=subplus(random('normal',0.00,0,Ne,1)); % 1
h_iHVA=subplus(random('normal',0.64,0,Ne,1)); % 1
m_iKm_E=subplus(random('normal',0.01,0,Ne,1)); % 1
% random ICs KCC2(-)
Bs(Npath)=random('normal',499.92,0,length(Npath),1); % mM buffer sould not be random
Cli(Npath)=subplus(random('normal',11.30,0,length(Npath),1)); % mM
Ko(Npath)=subplus(random('normal',3.46,0,length(Npath),1)); % mM
cai(Npath)=subplus(random('normal',0,0,length(Npath),1)); % mM
VD(Npath)=random('normal',-65.37,0,length(Npath),1); % mV
VSOMA=random('normal',-65.45,0,Ne,1); % mV
m_iKv(Npath)=random('normal',0.00,0,length(Npath),1); % 1
m_iNa(Npath)=random('normal',0.01,0,length(Npath),1); % 1
h_iNa(Npath)=random('normal',0.83,0,length(Npath),1); % 1
m_iNaD(Npath)=subplus(random('normal',0.01,0,length(Npath),1)); % 1
h_iNaD(Npath)=subplus(random('normal',0.84,0,length(Npath),1)); % 1
m_iNapD(Npath)=subplus(random('normal',0.00,0,length(Npath),1)); % 1
m_iKCa(Npath)=subplus(random('normal',0.00,0,length(Npath),1)); % 1
m_iHVA(Npath)=subplus(random('normal',0.00,0,length(Npath),1)); % 1
h_iHVA(Npath)=subplus(random('normal',0.58,0,length(Npath),1)); % 1
m_iKm_E=subplus(random('normal',0.01,0,Ne,1)); % 1
VSOMA=VD; % mV
VSOMA_sp=10*ones(Ne,1); % vector of refractory times, >t_ref
% REPRESENTATIVE CELLS
% KCC2 norm
VEnorm=zeros(1);
VEnorm_IE=zeros(1);
VEnorm_II=zeros(1);
Konorm=zeros(1);
Clinorm=zeros(1);
cai_VEnorm=zeros(1);
% KCC2 path
VEpath=zeros(1);
VEpath_IE=zeros(1);
VEpath_II=zeros(1);
Kopath=zeros(1);
Clipath=zeros(1);
cai_VEpath=zeros(1);
% LFP variable
LFP(1)=0;
% EXC Firings
firings_E=[]; % spike timings
fired_E=[]; % indexes of spikes fired at t
% SYNAPTIC CONNECTIONS
IE=0;
II=0;
% EE, AMPA
gEE_AMPA=zeros(Ne,1);
% EE, NMDA
gEE_NMDA=zeros(Ne,1);
x_NMDA=zeros(Ne,1);
% EI, AMPA
gEI_AMPA=zeros(Ni,1);
% II, GABA
gII_GABA=zeros(Ni,1);
% IE, GABA
gIE_GABA=zeros(Ne,1);
%% EXTERNAL SYNAPTIC INPUT TO ONE NEURON
% GABA
ggGABA_ext=0;
gGABA_ext=0;
% AMPA
ggAMPA_ext=0;
gAMPA_ext=0;
% NMDA
ggNMDA_ext=0;
gNMDA_ext=0;
ts=100; % moment of the first stimuli
dts=ts; % next stimulation interval, ts+dts
% GABA-A
alpha1_GABA=0.1; % kHz
alpha2_GABA=0.1; % kHz
%AMPA
alpha1_AMPA=0.5; % kHz
alpha2_AMPA=0.5; % kHz
V_AMPA=5; % mV
%NMDA
alpha1_NMDA=0.05; % kHz
alpha2_NMDA=0.05; % kHz
VNMDA=10; % mV
gGABA_max=3; % mS/cm^2, estimated from Chizhov 2
gAMPA_max=1; % mS/cm^2, estimated from Chizhov 3
gNMDA_max=2; % mS/cm^2
%%
%% TIME INTEGRATION LOOP
for t=1:1:round(T/dt)
% ALGEBRAIC EQUATIONS
% Na-P-pump
Ap=(1/((1+(Naialpha/Nai))^3))*(1./((1+(Koalpha./Ko)).^2));
Ikpump=-2*Imaxsoma*Ap;
INapump=3*Imaxsoma*Ap;
% reversal potentials on soma and dendrite
% K
VKe=e0*log(Ko/Ki_e);
% NA
VNAe=e0*log(Nao/Nai);
% CL
VCL=e0*log(Cli/Clo);
VGABA=e0*log((4*Cli+HCO3i)./(4*Clo+HCO3o));
if t*dt<=Tst % stimulation only during the stimulation period
if t*dt==ts % generation of stimulus times
delta_I=1/dt;
delta_E=1/dt;
ts=ts+dts;
else
delta_I=0;
delta_E=0;
end
else % count the seizure duration after the stimulus
ts=0;
delta_I=0;
delta_E=0;
end
% GABA ext
gGABA_ext(t+1)=ggGABA_ext(t)*dt + gGABA_ext(t);
ggGABA_ext(t+1)=(alpha1_GABA.*alpha2_GABA.*( delta_I.*(1-gGABA_ext(t))./K(alpha1_GABA,alpha2_GABA)-gGABA_ext(t)-(1/alpha1_GABA +1/alpha2_GABA).*ggGABA_ext(t))).*dt +ggGABA_ext(t);
% AMPA ext
gAMPA_ext(t+1)=ggAMPA_ext(t)*dt + gAMPA_ext(t);
ggAMPA_ext(t+1)=(alpha1_AMPA.*alpha2_AMPA.*( delta_E.*(1-gAMPA_ext(t))./K(alpha1_AMPA,alpha2_AMPA)-gAMPA_ext(t)-(1/alpha1_AMPA +1/alpha2_AMPA).*ggAMPA_ext(t))).*dt +ggAMPA_ext(t);
% NMDA ext
gNMDA_ext(t+1)=ggNMDA_ext(t)*dt + gNMDA_ext(t);
ggNMDA_ext(t+1)=(alpha1_NMDA.*alpha2_NMDA.*( delta_E.*(1-gNMDA_ext(t))./K(alpha1_NMDA,alpha2_NMDA)-gNMDA_ext(t)-(1/alpha1_NMDA +1/alpha2_NMDA).*ggNMDA_ext(t))).*dt +ggNMDA_ext(t);
% dendrite current
f_NMDA=1/(1+Mg/3.57*exp(-0.062*VD(450)));
iDendrite= -G_lD*(VD-VCL) -G_kl*(VD-VKe) -G_Nal*(VD-VNAe) -2.9529*G_NaD*m_iNaD.^3.*h_iNaD.*(VD-VNAe) -G_NapD*m_iNapD.*(VD-VNAe) -G_KCa*m_iKCa.^2.*(VD-VKe) -2.9529*G_HVA*m_iHVA.^2.*h_iHVA.*(VD-E_Ca) -2.9529*G_Km_E*m_iKm_E.*(VD-VKe) -INapump -Ikpump;
iDendrite(450)=iDendrite(450) -gNMDA_max*gNMDA_ext(t)*f_NMDA*(VD(450)-VNMDA) -gGABA_max*gGABA_ext(t)*(VD(450)-VGABA(450)) -gAMPA_max.*gAMPA_ext(t)*(VD(450)-V_AMPA);
% somatic voltage
g1_SOMA=gg_kl +gg_Nal +(2.9529*G_Na*m_iNa.^3.*h_iNa) +(2.9529*G_Kv.*m_iKv);
g2_SOMA=gg_kl*VKe +gg_Nal*VNAe +(2.9529*G_Na*m_iNa.^3.*h_iNa*VNAe) +(2.9529*G_Kv*m_iKv.*VKe) -INapump -Ikpump;
VSOMA=(VD + (kappa*S_Soma *g2_SOMA)) ./ (1+kappa*S_Soma*g1_SOMA);
% IKv Soma
a_iKv=0.02*(VSOMA-Vbolz_E)./(1-exp(-(VSOMA-Vbolz_E)/9));
b_iKv=-0.002*(VSOMA-Vbolz_E)./(1-exp((VSOMA-Vbolz_E)/9));
tauKvm=1./((a_iKv+b_iKv)*2.9529);
infKvm=a_iKv./(a_iKv+b_iKv);
% INa Soma
am_iNa=0.182*(VSOMA-10+35)./(1-exp(-(VSOMA-10+35)/9));
bm_iNa=0.124*(-VSOMA+10-35)./(1-exp(-(-VSOMA+10-35)/9));
ah_iNa=0.024*(VSOMA-10+50)./(1-exp(-(VSOMA-10+50)/5));
bh_iNa=0.0091*(-VSOMA+10-75)./(1-exp(-(-VSOMA+10-75)/5));
tau_m=(1./(am_iNa+bm_iNa))/2.9529;
tau_h=(1./(ah_iNa+bh_iNa))/2.9529;
m_inf_new=am_iNa./(am_iNa+bm_iNa);
h_inf_new=1./(1+exp((VSOMA-10+65)/6.2));
% NaP, D current
minfiNapD = 0.02./(1 + exp(-(VD+42)/5));
% INa D, sodium channel
am_iNaD=0.182*(VD-10+35)./(1-exp(-(VD-10+35)/9));
bm_iNaD=0.124*(-VD+10-35)./(1-exp(-(-VD+10-35)/9));
ah_iNaD=0.024*(VD-10+50)./(1-exp(-(VD-10+50)/5));
bh_iNaD=0.0091*(-VD+10-75)./(1-exp(-(-VD+10-75)/5));
minf_newD = am_iNaD./(am_iNaD+bm_iNaD);
hinf_newD = 1./(1+exp((VD-10+65)/6.2));
tau_mD = (1./(am_iNaD+bm_iNaD))/2.9529;
tau_hD = (1./(ah_iNaD+bh_iNaD))/2.9529;
%%%% iKCa %%%%
minf_iKCa = (48*cai.^2/0.03)./(48*cai.^2/0.03 + 1);
taum_iKCa = (1./(0.03*(48*cai.^2/0.03 + 1)))/4.6555;
%%%% IHVA %%%%
am_iHVA = 0.055*(-27 - VD)./(exp((-27-VD)/3.8) - 1);
bm_iHVA = 0.94*exp((-75-VD)/17);
ah_iHVA = 0.000457*exp((-13-VD)/50);
bh_iHVA = 0.0065./(exp((-VD-15)/28) + 1);
tauHVAh = 1./((ah_iHVA+bh_iHVA)*2.9529);
infHVAh = ah_iHVA./(ah_iHVA+bh_iHVA);
tauHVAm = 1./((am_iHVA+bm_iHVA)*2.9529);
infHVAm = am_iHVA./(am_iHVA+bm_iHVA);
%%% IKM %%%%
am_iKm_E = 0.001*(VD + 30)./(1 - exp(-(VD + 30)/9));
bm_iKm_E = -0.001*(VD + 30)./(1 - exp((VD + 30)/9));
tauKmm_E = 1./((am_iKm_E+bm_iKm_E)*2.9529);
infKmm_E = am_iKm_E./(am_iKm_E+bm_iKm_E);
% ION CURRENTS
ICL = G_lD*(VD-VCL);
ICL((450))=ICL((450)) + gGABA_max*gGABA_ext(t)*(VD(450)-VGABA(450));
IK = gg_kl*(VSOMA-VKe) +G_kl*(VD-VKe) +G_KCa*m_iKCa.*m_iKCa.*(VD-VKe) +2.9529*G_Km_E.*m_iKm_E.*(VD-VKe) +(2.9529*G_Kv*m_iKv.*(VSOMA-VKe))/200;
% GLIA
kon=koff./(1+exp((Ko-Kothsoma)/(-1.15)));
Glia=koff*(Bmax-Bs)/K1n -kon/K1n.*Bs.*Ko;
% EULER METHOD
VD=((1/Cm).*(iDendrite +(VSOMA-VD) / (kappa*S_Dend)))*dt + VD;
m_iNa=(-(m_iNa-m_inf_new)./tau_m)*dt + m_iNa;
h_iNa=(-(h_iNa-h_inf_new)./tau_h)*dt + h_iNa;
m_iKv=(-(m_iKv-infKvm)./tauKvm)*dt + m_iKv;
m_iNaD =(-(m_iNaD - minf_newD)./tau_mD)*dt +m_iNaD;
h_iNaD =(-(h_iNaD - hinf_newD)./tau_hD)*dt +h_iNaD;
m_iNapD=(-(m_iNapD - minfiNapD)./0.1992)*dt +m_iNapD;
m_iKCa =(-(1./taum_iKCa).*(m_iKCa - minf_iKCa))*dt + m_iKCa;
m_iHVA = (-(m_iHVA-infHVAm)./tauHVAm)*dt + m_iHVA;
h_iHVA = (-(h_iHVA-infHVAh)./tauHVAh)*dt + h_iHVA;
m_iKm_E = (-(m_iKm_E-infKmm_E)./tauKmm_E)*dt + m_iKm_E;
% ION CONCENTRATION CHANGES %
Ko=(kK/F/d*(IK +Ikpump +Ikpump -Ikcc2.*(VKe-VCL)./((VKe-VCL)+Vhalf)) +Glia +D/dx^2.*(sum(Ko(l),2)-4*Ko) )*dt + Ko;
Cli=kCL/F*(ICL +Ikcc2.*(VKe-VCL)./((VKe-VCL)+Vhalf) )*dt + Cli;
cai=(-5.1819e-5*2.9529*G_HVA*m_iHVA.^2.*h_iHVA.*(VD-E_Ca)/DCa + (0.00024-cai)./TauCa)*dt + cai;
% Glial buffer
Bs=(koff.*(Bmax-Bs) -kon.*Bs.*Ko)*dt + Bs;
fired_E=find(VSOMA>=0); % indices of spikes in the network for one time step
% Processing of fired_E
INT_E=intersect(find(VSOMA_sp<t_ref),fired_E); % intersection VSOMA_sp<2 and fired_E
fired_E=setxor(fired_E,INT_E); % remove fired_E elements that intersect with VSOMA_sp<2
VSOMA_sp=VSOMA_sp + dt; % update time for t* vector
VSOMA_sp(fired_E)=0;
% Record firings
firings_E=[firings_E; t+0*fired_E,fired_E];
%fr_E(t)=sum(fired_E)/dt/Ne; % E pop rate
% REPRESENTATIVE NORM EXC CELL
VEnorm(t)=VSOMA(450);
Konorm(t)=Ko(450);
Clinorm(t)=Cli(450);
VEnorm_IE(t)=gEE_AMPA(450)*(V_AMPA-VD(450));
VEnorm_II(t)=gIE_GABA(450)*(VGABA(450)-VD(450));
cai_VEnorm(t)=cai(450);
%%%% LFP MODEL %%%%
LFP(t)=k*( sum((VSOMA-VD)/(kappa*S_Dend)) );
%%ONLINE PLOTTING
%{
if (t-1)*dt==Tframe
%%
figure('units','normalized','position',[.1 .1 .6 .8]);
% PLOT
subplot(2,2,1);
imagesc((reshape(VSOMA,sqrt(Ne),sqrt(Ne)))', [-80 60]);
axis image;
set(gca,'FontSize',20); % set the axis with big font
set(gca,'Ydir','normal');
title(sprintf('E population, T=%dms',Tframe));
xlabel('cell index');
ylabel('cell index');
h1=colorbar;
h1.Label.String = 'Voltage, mV';
colormap jet;
subplot(2,2,2);
imagesc((reshape(VI,sqrt(Ni),sqrt(Ni)))', [-80 60]);
axis image;
set(gca,'FontSize',20); % set the axis with big font
set(gca,'Ydir','normal');
title(sprintf('I population, T=%dms',Tframe));
set(gca,'FontSize',20); % set the axis with big font
xlabel('cell index');
ylabel('cell index');
h2=colorbar;
h2.Label.String = 'Voltage, mV';
subplot(2,2,3);
imagesc((reshape(Ko,sqrt(Ne),sqrt(Ne)))', [3 5]);
axis image;
%pcolor((reshape(Ko,sqrt(Ne),sqrt(Ne)))');
set(gca,'FontSize',20); % set the axis with big font
set(gca,'Ydir','normal');
title(sprintf('K^+_{Out}, T=%d ms',Tframe));
xlabel('cell index');
ylabel('cell index');
h3=colorbar;
h3.Label.String = 'Concentration, mM';
subplot(2,2,4);
imagesc((reshape(Cli,sqrt(Ne),sqrt(Ne)))',[5 20]);
axis image;
%pcolor((reshape(Cli,sqrt(Ne),sqrt(Ne)))');
set(gca,'FontSize',20); % set the axis with big font
set(gca,'Ydir','normal');
title(sprintf('Cl^-_{In}, T=%dms',Tframe));
xlabel('cell index');
ylabel('cell index');
h4=colorbar;
h4.Label.String = 'Concentration, mM';
% Record the Ko movie
MOV(frame)=getframe(gcf);
% closing the figure
close figure 1
frame=frame+1; % counter for the movie
Tframe=Tframe + dTframe;
end
%}
end
%%%%%% END OF PLOTTING PART %%%%%%
%% Final Plotting
time=(1:1:t).*dt;
figure('units','normalized','outerposition',[0 0 1 1]);
% PLOT
subplot(2,2,1);
imagesc((reshape(Ko,sqrt(Ne),sqrt(Ne)))'); % ,[3 8]
set(gca,'Ydir','normal');
%imagesc((reshape(VK,sqrt(Ne),sqrt(Ne)))');
set(gca,'FontSize',20); % set the axis with big font
ylabel('Cell index');
xlabel('Cell index');
title('K_{OUT}, mM');
%title('VK, mV');
colormap jet;
colorbar;
box off;
subplot(2,2,2);
imagesc((reshape(Cli,sqrt(Ne),sqrt(Ne)))'); % ,[5 25]
set(gca,'Ydir','normal');
ylabel('Cell index');
xlabel('Cell index');
%imagesc((reshape(VGABA,sqrt(Ne),sqrt(Ne)))');
set(gca,'FontSize',20); % set the axis with big font
title('Cl_{IN}, mM');
%title('VGABA, mV');
colorbar;
box off;
subplot(2,2,3);
plot(Konorm,Clinorm,'blue',Ko1,Cli1,'black',Ko2,Cli2,'black',Konorm(1),Clinorm(1),'Markersize',40);
axis([0 30 0 30]);
set(gca,'FontSize',30); % set the axis with big font
xlabel('Ko, mM');
ylabel('Cli, mM');
title('KCC2(+)');
box off;
subplot(2,2,4);
plot(time,VEnorm,time,VEpath);
set(gca,'FontSize',20); % set the axis with big font
ylabel('V_E, mV');
box off;
SIMULATION_TIME=toc % end of timer