Respiratory control model with brainstem CPG and sensory feedback (Diekman, Thomas, and Wilson 2017)

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Accession:229640
This is a closed-loop respiratory control model incorporating a central pattern generator (CPG), the Butera-Rinzel-Smith (BRS) model, together with lung mechanics, oxygen handling, and chemosensory components. The closed-loop system exhibits bistability of bursting and tonic spiking. Bursting corresponds to coexistence of eupnea-like breathing, with normal minute ventilation and blood oxygen level. Tonic spiking corresponds to a tachypnea-like state, with pathologically reduced minute ventilation and critically low blood oxygen. In our paper, we use the closed-loop system to demonstrate robustness to changes in metabolic demand, spontaneous autoresuscitation in response to hypoxia, and the distinct mechanisms that underlie rhythmogenesis in the intact control circuit vs. the isolated, open-loop CPG.
Reference:
1 . Diekman CO, Thomas PJ, Wilson CG (2017) Eupnea, tachypnea, and autoresuscitation in a closed-loop respiratory control model. J Neurophysiol 118:2194-2215 [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: Brainstem;
Cell Type(s): Respiratory column neuron; PreBotzinger complex neuron;
Channel(s): I Na,p; I Na,t; I K;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: MATLAB; XPP;
Model Concept(s): Pacemaking mechanism; Respiratory control;
Implementer(s): Diekman, Casey O. [casey.o.diekman at njit.edu];
Search NeuronDB for information about:  I Na,p; I Na,t; I K;
% This script recreates Figure 10 by simulating instantaneous arterial oxygen tension (PaO2) clamp in the closed-loop model, and reading in bifurcation
% curves pre-computed in XPPAUT. To generate the bifurcation curves use the XPP code "generate_figure11_bifurcation_curves.ode"

clear all

%% simulate closed-loop with instantaneous arterial oxygen tension (PaO2) clamp

% Initial conditions [V n h alpha vollung PO2lung PO2blood]
inits1=[-50.001086299999997 0.005214749336000 0.515241494700000 0.000785233164600 2.178562104000000 77.395450929999996 76.9];

t0=0;
tf1=60*1000; tf2=tf1*2; tf3=tf1*3; tf4=tf1*4; tf5=tf1*5; tf6=tf1*6; tf7=tf1*7; tf8=tf1*8; tf9=tf1*9; tf10=tf1*10;

options=odeset('RelTol',1e-8,'AbsTol',1e-8);

[t1,u1]=ode15s('closedloop',[t0 tf1],inits1,options);

inits2=u1(end,:);
[t2,u2]=ode15s('closedloop',[tf1 tf2],inits2,options);

inits3=u2(end,:);
[t3,u3]=ode15s('closedloop',[tf2 tf3],inits3,options);

inits4=u3(end,:);
inits4(end)=40;
[t4,u4]=ode15s('closedloop',[tf3 tf4],inits4,options);

inits5=u4(end,:);
[t5,u5]=ode15s('closedloop',[tf4 tf5],inits5,options);

inits6=u5(end,:);
[t6,u6]=ode15s('closedloop',[tf5 tf6],inits6,options);

inits7=u6(end,:);
inits7(end)=30;
[t7,u7]=ode15s('closedloop',[tf6 tf7],inits7,options);

inits8=u7(end,:);
[t8,u8]=ode15s('closedloop',[tf7 tf8],inits8,options);

inits9=u8(end,:);
[t9,u9]=ode15s('closedloop',[tf8 tf9],inits9,options);

inits10=u9(end,:);
[t10,u10]=ode15s('closedloop',[tf9 tf10],inits10,options);

t=[t1; t2; t3; t4; t5; t6; t7; t8; t9; t10];
u=[u1; u2; u3; u4; u5; u6; u7; u8; u9; u10];

v=u(:,1);
h=u(:,3);
vol=u(:,5);
po2blood=u(:,7);
gtonic=0.3*(1-tanh((po2blood-85)./30));

regburstmin=177270-4900;
regburstmax=178570;

regburstInds=find(t>=regburstmin & t<=regburstmax); 

bigburstmin=t(regburstInds(9679));
bigburstmax=181200;

bigburstInds=find(t>=bigburstmin & t<=bigburstmax);

%% read in pre-computed bifurcation curves (generated in XPPAUT, see generate_figure4_bifurcation_curves.ode)

% panel C top

dataB=dlmread('data_figure4/figure4_panelB_fastsystem_h_bifdiag_gtonic0pt1247.dat'); % cyan
dataC=dlmread('data_figure4/figure4_panelC_fastsystem_h_bifdiag_gtonic0pt2194.dat'); % green
dataD=dlmread('data_figure4/figure4_panelD_fastsystem_h_bifdiag_gtonic0pt1806.dat'); % magenta

% panel C bottom

dataG=dlmread('data_figure10/figure10_panelC_fastsystem_h_bifdiag_gtonic0pt5709.dat'); % green
dataM=dlmread('data_figure10/figure10_panelC_fastsystem_h_bifdiag_gtonic0pt3461.dat'); % magenta

hB=dataB(:,1); hC=dataC(:,1); hD=dataD(:,1); hG=dataG(:,1); hM=dataM(:,1);
vB=dataB(:,2); vC=dataC(:,2); vD=dataD(:,2); vG=dataG(:,2); vM=dataM(:,2);


%% make plots

set(0,'DefaultAxesFontSize',24)

lw=2;

%% panel A

figure(1)

xlo=169000;
xhi=188000;

subplot(4,1,1)
hold on
plot(t/1000,po2blood,'k','Linewidth',lw)
xlim([xlo/1000 xhi/1000])
ylim([30 120])
set(gca,'XTickLabel',[],'YTick',[40 80 120])
ylabel('$P_aO_2$','Interpreter','latex')

subplot(4,1,2)
hold on
plot(t/1000,gtonic,'k','Linewidth',lw)
xlim([xlo/1000 xhi/1000])
ylim([0 .61])
set(gca,'XTickLabel',[],'YTick',[0 .3 .6])
ylabel('$g_\mathrm{tonic}$','Interpreter','latex')

subplot(4,1,3)
hold on
plot(t/1000,v,'k')
xlim([xlo/1000 xhi/1000])
ylim([-70 20])
set(gca,'XTickLabel',[],'YTick',[-60 -20 20])
ylabel('$V$','Interpreter','latex')

subplot(4,1,4)
hold on
plot(t/1000,vol,'k','Linewidth',lw)
xlim([xlo/1000 xhi/1000])
set(gca,'YTick',[2 3.5 5])
ylim([1.9 5.5])
ylabel('$\mathrm{vol}_\mathrm{L}$','Interpreter','latex')
xlabel('$t$ (s)','Interpreter','Latex')

%% panel B

figure(2)
subplot(2,1,1)
hold on
plot(t/1000,v,'k','Linewidth',lw)
xlim([177.27 178.57])
ylim([-65 15])
ylabel('$V$','Interpreter','latex')
set(gca,'box','off','YTick',[-60:30:0],'XTick',[177.37:.4:178.57],'XTickLabel',{'177.4' '177.8' '178.2' '178.6'})
xlabel('$t$ (s)','Interpreter','latex')

subplot(2,1,2)
hold on
plot(t/1000,v,'k','Linewidth',lw)
xlim([179.9 181.2])
ylim([-65 15])
ylabel('$V$','Interpreter','latex')
set(gca,'box','off','YTick',[-60:30:0],'XTick',[180:.4:181.2],'XTickLabel',{'180.0' '180.4' '180.8' '181.2'})
xlabel('$t$ (s)','Interpreter','latex')

%% panel C

figure(3)
subplot(2,1,1)
plot(hB(2:110),vB(2:110),'c','Linewidth',2)
hold on
plot(hB(110:310),vB(110:310),'k','Linewidth',1)
plot(hC(2:118),vC(2:118),'g','Linewidth',2)
plot(hC(118:318),vC(118:318),'k','Linewidth',1)
plot(hD(2:114),vD(2:114),'m','Linewidth',2)
plot(hD(114:314),vD(114:314),'k','Linewidth',1)
plot(h(regburstInds),v(regburstInds),'k')
xlim([0.2 1])
ylim([-70 10])
xlabel('$h$','Interpreter','latex')
ylabel('$V$','Interpreter','latex')
set(gca,'box','off')

subplot(2,1,2)
plot(hB(2:110),vB(2:110),'c','Linewidth',2)
hold on
plot(hB(110:310),vB(110:310),'k','Linewidth',1)
plot(hG(2:143),vG(2:143),'g','Linewidth',2)
plot(hG(143:243),vG(143:243),'k','Linewidth',1)
plot(hM(2:126),vM(2:126),'m','Linewidth',2)
plot(hM(126:327),vM(126:327),'k','Linewidth',1)
plot(h(bigburstInds),v(bigburstInds),'k')
xlim([0.2 1])
ylim([-70 10])
xlabel('$h$','Interpreter','latex')
ylabel('$V$','Interpreter','latex')
set(gca,'box','off')

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