Multiscale model of olfactory receptor neuron in mouse (Dougherty 2009)

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Accession:136097
Collection of XPP (.ode) files simulating the signal transduction (slow) and action potential (fast) currents in the olfactory receptor neuron of mouse. Collection contains model configured for dual odorant pulse delivery and model configured for prolonged odorant delivery. For those interested more in transduction processes, each whole cell recording model comes with a counter part file configured to show just the slow transduction current for ease of use and convenience. These transduction-only models typically run faster than the full multi-scale models but do not demonstrate action potentials.
Reference:
1 . Dougherty DP (2009) Workshop: Computational Problems in Sequential Stages of Odor Processing. Modeling Diversity in the Signal Transduction of the Mouse Olfactory Receptor Neuron. Abstracts from the Thirty-first Annual Meeting of the Association for Chemoreception Sciences AChemS:A13-A13
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Axon; Dendrite;
Brain Region(s)/Organism:
Cell Type(s): Olfactory receptor GLU cell;
Channel(s): I K; I Cl,Ca; I CNG; Na/Ca exchanger; I_Na,Ca; I_K,Na; I ANO2;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s): Ions;
Simulation Environment: XPPAUT;
Model Concept(s): Action Potential Initiation; Oscillations; Parameter Fitting; Simplified Models; Axonal Action Potentials; Action Potentials; Signaling pathways; G-protein coupled; Multiscale; Olfaction;
Implementer(s): Dougherty, Daniel P [dpdoughe at mbi.ohio-state.edu];
Search NeuronDB for information about:  Olfactory receptor GLU cell; I K; I Cl,Ca; I CNG; Na/Ca exchanger; I_Na,Ca; I_K,Na; I ANO2; Ions; 
#D.P.Dougherty 2010
#Spiking model of mouse ORN
#This is a multi-scale extension of the model in Dougherty et al 2005. PNAS 102(30):10415-10420
#which includes cilium, dendrite, and soma compartments.
#
#The XPP file is configured to demonstrate a dual-pulse stimulation protocol
#with whole cell suction pipette recording showing the slow transduction
#current and fast action potentials generated.
#

#Alphabetically sorted listing of all model parameters (descriptions given below).

param cap=0.0035
param cc1lin=0.6362
param cc2=20.9869
param ck1lin=10.3615
param ck2=0.5833
param clmax=0.8294
param cnmax=3.6417
param ef=7.9725
param gl=15.4267
param hmc1=1.5965
param hmc2=7.6415
param inf=1.4654
param inhmax=0.98
param k1=2.2748
param k2lin=42.0896
param kI=16.5304
param kinh=1.3875
param kinhcng=0.2242
param n1=5.6384
param n2=3.4161
param ninh=0.4067
param ninhcng=0.6306
param pd=15.4669
param r1=9.4574
param r2=12.5485
param smax=63.0987
param vcl=-7.3248
param vcng=0.4641
param vl=-69.6653

#Spiking aspect of the model -- dendrite and soma parameters.
param ge1=70.244          
param ge2=20.245          
param tau_soma=6100       
param epsilon=0.09        
param beta=0.092          
param beta_cap=0.95          
param cap_max=400.5      
param cap_off=-75         
param gamma=43.92         
param VSspike=-58.23     
param VSamp=14.36         
param vd=0.05   


#Parameters descriptions with their units.
#
#cap	  #Capacitance of ORN ciliary membrane# nF 										   
#cc1lin   #Rate at which Ca2+ associates with CaM to form CaCaM # s^-1							   
#cc2	  #Rate at which CaCaM dissociates to Ca2+ and CaM # s^-1 							   
#ck1lin   #Rate at which CaCaM activates CaMK	# s^-1								   
#ck2	  #Rate at which active CaMK deactivates # s^-1										   
#clmax    #Maximal conductance of ANO2 Cl(Ca) channels # nS								   
#cnmax    #Maximal conductance of CNG channels # nS							   
#ef	  #Maximum calcium efflux (assumed sodium & potassium independent) #s^-1				   
#gl	  #Maximum leak (generic) conductance # nS									   
#hmc1	  #Concentration of cAMP needed to achieve half-maximal activation (K1/2) of the CNG channel # uM						   
#hmc2	  #Concentration of Ca2+ needed to achieve half-maximal activation (K1/2) of the Cl(Ca) channel| # uM							   
#inf	  #Net calcium inward flux via CNG channel # uM*pC^-1								   
#inhmax   #Maximum inhibition of CNG by CaCAM # unitless								   
#k1	  #Receptor affinity for ligand # (um*s)^-1								   
#k2lin    #Rate of G-protein activation per bound receptor complex  # s^-1						   
#kinh	  #Concentration of aCaMK needed for half-maximal inhibition (IC50) of cAMP production # uM							   
#kinhcng  #Concentration of CaCaM needed for half-maximal inhibition of the CNG channel # uM							   
#n1	  #Hill coefficient of the CNG channel activation function #	unitless						   
#n2	  #Hill coefficient of the Cl(Ca) channel activation function	# unitless							   
#ninh	  #Steepness of the decreasing sigmoid representing aCaMK-mediated inhibition of cAMP synthesis	 # unitless					   
#ninhcng  #Steepness of the sigmoid inhcng representing inhibition of CNG channel by CaCaM # unitless				   
#pd	  #Rate at which a cAMP molecule is degraded by phosphodiesterase # s^-1									   
#r1	  #Rate of unbinding of odorant from receptor	 # s^-1								   
#r2	  #Rate at which a G-protein becomes deactivate rate # s^-1								   
#smax	  #Maximal (uninhibited) rate of cAMP production by adenylyl cyclase per active G-protein # uM*s^-1						   
#vcl	  #Reversal potential of Cl(Ca) channels  # mV							   
#vcng	  #Reversal potential of CNG channels # mV								   
#vl	  #Effective reversal potential for leak current # mV 							   
#ge1	  #Coupling strength between cilia and dendrite compartments	# s^-1				   
#ge2	  #Coupling strength between dendrite and soma compartments 	# mV^-1				   
#tau_soma #Relative time scale of soma to cilia dynamics #s^-1						   
#epsilon  #Relative time scale of Na and K channel dynamics to voltage dynamics in soma #Unitless		   
#beta	  #Sharpness of Na and K channel response to voltage	# mV					   
#beta_cap #Sharpness of soma capacitance dependence on voltage  # mV					   
#cap_max  #Maximum soma capacitance	# nF 							   
#cap_off  #Voltage at which soma capacitance is half maximal	#mV					   
#gamma    #Na and K channel activation rate (sets height of channel manifold)	#unitless			   
#VSspike  #Reference voltage for action potentials by soma # mV						   
#VSamp    #Sharpness of soma voltage response #mV								   
#vd	  #Diffusive dendritic voltage leak/loss. #s^-1					   
 
 
 
#Now parameters related to the experimental design: 
 
#Micromolar concentration of odorant at full concentration
#Feel free to play with this!!

param ostim=100 

#hv defines a heaviside-like pulse but with adjustable steepness parameter.  
#Use this to describe a "smeared" square wave odorant plume reaching the neuron.
#Sharpness of odorant plume          
param SHARPNESS=0.0001    
hv(x,s)=1/(1+exp(-x/s))
#Pulse comes on for 1s at t=1 then on again for 1s at t=5.
PULSE(t)=(hv(t-1,SHARPNESS) - hv(t-2,SHARPNESS) + (hv(t-5,SHARPNESS) - hv(t-6,SHARPNESS)))			   
OD(t) = ostim*PULSE(t)

#The vertebrate ORN model has 3 compartments i) Cilia, ii) Dendrite, and iii) Soma.
#### Cilia Compartment ####
dbLR/dt       = k1*OD(t)*(1-bLR)-r1*bLR
daG/dt        = k2lin*bLR*(1-aG) - r2*aG
dcAMP/dt      = (aG*smax)/(1 + ((CAMK/kinh)^ninh)) - pd*cAMP
dCa/dt        = inf*Icng(cAMP,Vcilia) - ef*Ca + (-cc1lin*Ca + cc2*CaCAM)
dCaCAM/dt     = cc1lin*Ca - cc2*CaCAM
dCAMK/dt      = ck1lin*CaCAM - ck2*CAMK
dVcilia/dt    = (1/cap)*(Icng(cAMP,Vcilia) + Icacl(Ca,Vcilia) + Il(Vcilia))

#### Dendrite Compartment ####
dVdend/dt     = ge1*(Vcilia-Vdend) - vd*Vdend

#### Soma Compartment ####
dVsoma/dt     = VOLTAGE(V(Vsoma),Vcilia,Vdend)
dNaKXsoma/dt  = tau_soma*(epsilon*(gamma*(1+tanh(V(Vsoma)/beta))-NaKXsoma))


Input(x,y)  = ge2*(x-y)
V(x)      = (x-VSspike)/(0.5*VSamp)
VOLTAGE(x,y,z) = tau_soma*(3*x - x^3 + 2 - NaKXsoma + Input(y,z))

inhcng(CaCAM) = 1+(inhmax-1)*((CaCAM^ninhcng)/(CaCAM^ninhcng + kinhcng^ninhcng))

#Current models:
Icng(cAMP,Vcilia) = ((cnmax*cAMP^n1)/(cAMP^n1 + (inhcng(CaCAM)*hmc1)^n1))*(vcng-Vcilia)
Icacl(Ca,Vcilia)  = ((clmax*Ca^n2)/(Ca^n2 + hmc2^n2))*(vcl-Vcilia)
Il(Vcilia)     = gl*(vl-Vcilia)
cap_soma(Vcilia) = cap_max*(1+tanh((cap_off-Vcilia)/beta_cap))
Isoma(x,y,z)  = cap_soma(Vcilia)*VOLTAGE(x,y,z)


#These auxilliary functions simply model what is actually measured by suction pipette recording
#from whole cell.

aux Icilia=-(Icng(cAMP,Vcilia) + Icacl(Ca,Vcilia))
aux WholeCell=Isoma(V(Vsoma),Vcilia,Vdend) -(Icng(cAMP,Vcilia) + Icacl(Ca,Vcilia))
aux Odorant=100*PULSE(t)
#The number 100 is used above simply to give the odorant pulses a nice magnitude when plotted in the 
#same axes as the currrents.  Unfortunately XPP does not have real double y-axis plots.
#Anyway, at least you can see the odorant pulses now!

#Initial conditions.  Note that we actually run the model to steady-state in the absence 
#of odorant for 1s before simulation of the experiment. See T0 option below.  
#

init bLR=1.e-8
init aG=1.e-8
init cAMP=1.e-8
init Ca=1.e-8
init CaCAM=1.e-8
init CAMK=1.e-8
init Vcilia=vl
init Vdend=vl
init Vsoma=vl
init NaKXsoma=3.e-8

@ BUT=RunModel:ig,BUT=FitAxes:wf,MAXSTOR=2000000,T0=-1,TOTAL=8.0,BOUND=1000000
@ meth=cvode,TOL=1e-5,ATOL=1e-5,T0=-1,DT=0.00001,DTMIN=0.0001,DTMAX=0.001
@ XLO=0,XHI=8,YLO=-250,YHI=150
@ NPLOT=2,YP=WholeCell,YP2=Odorant

done

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