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;
## Steps to generate the bifurcation curves shown in Figure 11 panel C:
## 1) Load this .ode file into XPPAUT 
## 2) For the top part of panel C, set gtonic to 0.12 for cyan curve, 0.22 for green curve, and 0.18 magenta curve
## 3) For the bottom part of panel C, set gtonic to 0.57 for green curve and 0.35 for magenta curve (cyan curve is same as top)
## 3) Keystrokes to run simulation and compute bifurcation curve: (i)(g)(i)(l)(f)(a)(r)(s)
## 4) Keystrokes to save the data: (f)(w), and then click on Ok 

# BRS model fast subsystem with h as bifurcation parameter
par h=-2

# Set gtonic as described above for accordingly for panel C
par gtonic=0.1247
#par gtonic=0.2194
#par gtonic=0.1806
#par gtonic=0.5709
#par gtonic=0.3461

# parameters
par i=0,c=21,etonic=0
par gl=2.8,el=-65
par gna=28,ena=50
par gk=11.2,ek=-85
par gnap=2.8

# gating functions
xinf(v,vt,sig)=1/(1+exp((v-vt)/sig))
taux(v,vt,sig,tau)=tau/cosh((v-vt)/(2*sig))

# persistent sodium
pinf(v)=xinf(v,-40,-6)
inap=gnap*pinf(v)*h*(v-ena)

# transient sodium 
minf(v)=xinf(v,-34,-5)
ina=gna*minf(v)^3*(1-n)*(v-ena)

# potassium
ninf(v)=xinf(v,-29,-4)
taun(v)=taux(v,-29,-4,10)
ik=gk*n^4*(v-ek)

# leak
il=gl*(v-el)

# tonic
itonic=gtonic*(v-etonic)

# differential equations
v' = (i-il-ina-ik-inap-itonic)/c
n'=(ninf(v)-n)/taun(v)

init v=-60

# XPP settings
@ total=40000,dt=.1,meth=cvode,maxstor=10000000
@ tol=1e-8,atol=1e-8
@ xlo=0,xhi=40000,ylo=-80,yhi=20

# AUTO settings
@ parmin=-100,parmax=100,autoxmin=-2,autoxmax=2,autoymin=-80,autoymax=20
@ dsmin=1e-4,dsmax=.1,nmax=500

done


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