Role of the AIS in the control of spontaneous frequency of dopaminergic neurons (Meza et al 2017)

 Download zip file   Auto-launch 
Help downloading and running models
Accession:235320
Computational modeling showed that the size of the Axon Initial Segment (AIS), but not its position within the somatodendritic domain, is the major causal determinant of the tonic firing rate in the intact model, by virtue of the higher intrinsic frequency of the isolated AIS. Further mechanistic analysis of the relationship between neuronal morphology and firing rate showed that dopaminergic neurons function as a coupled oscillator whose frequency of discharge results from a compromise between AIS and somatodendritic oscillators.
Reference:
1 . Meza RC, López-Jury L, Canavier CC, Henny P (2018) Role of the Axon Initial Segment in the Control of Spontaneous Frequency of Nigral Dopaminergic Neurons In Vivo. J Neurosci 38:733-744 [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: Basal ganglia; Mouse;
Cell Type(s): Substantia nigra pars compacta DA cell;
Channel(s): Na/K pump; I K,Ca; I K; I L high threshold; I T low threshold; I A; I N; I Na,t;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Activity Patterns; Temporal Pattern Generation; Oscillations; Pacemaking mechanism;
Implementer(s): Lopez-Jury, Luciana [lucianalopezjury at gmail.com]; Canavier, CC;
Search NeuronDB for information about:  Substantia nigra pars compacta DA cell; I Na,t; I L high threshold; I N; I T low threshold; I A; I K; I K,Ca; Na/K pump;
TITLE  squid sodium, potassium delayed rectifier, and potassium A channels
: Anna's version adding some shift values
	
 
UNITS {
        (molar) = (1/liter)
        (S) = (siemens)
        (mA) = (milliamp)
        (mV) = (millivolt)
         F = (faraday) (coulomb)
         R = (mole k) (mV-coulomb/degC)
        (mM) =  (millimolar)
}
 
NEURON {
        SUFFIX hh3
        USEION na READ nai WRITE ina
        USEION k WRITE ik
        RANGE  sshift, shift,gnabar,gkhhbar,gkabar,ina,ikhh,ika,ik,ena,gk,gna,gka
        GLOBAL minf,hinf,ninf
}
 
INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}
 
PARAMETER {
        v   (mV)
        dt  (ms)
	nai (mM)
	celsius = 35.0 (degC)
        gnabar  = 550.0e-6 (S/cm2)
        gkhhbar = 665.0e-6 (S/cm2)
        gkabar  = 266.0e-6  (S/cm2)
        ek  = -90.0  (mV)
        nao =  145  (mM)
        qv = 60.0 (mV)
        qs = 5.0  (1)
        shift=0 (mV)
        sshift=0 (mV)
 	
}
 
STATE {
        m <1e-4> h <1e-4> n <1e-4> p <1e-4> q <1e-4> 
}
 
ASSIGNED {
        ina (mA/cm2)
        ik (mA/cm2)
        ika (mA/cm2)
        ikhh (mA/cm2)
        ena (mV)
	minf hinf ninf qinf pinf 
	gna 
	gk 
	gka
}
 
BREAKPOINT {
        SOLVE states METHOD cnexp
	nai = 0.81
        ena = R*(celsius+273.15)/F*log(nao/nai)
	: ena=77.0
        ina = gnabar*m*m*m*h*(v - ena)
        ikhh = gkhhbar*n*n*n*(v - ek)      
        ika = gkabar*p*p*p*q*(v - ek)      
        ik = ika + ikhh
	gk = n*n*n
	gna = m*m*m*h
	gka = p*p*p*q
}
 
UNITSOFF
 
INITIAL {
        m = boltz(v,-34.6-shift,6.0-sshift)
        h = boltz(v,-56.8-shift,-7.8)
        n = boltz(v,-25.0,12.0)
        p = boltz(v,-43.0,24.0)
        q = boltz(v,-qv,-qs)
}

DERIVATIVE states {  :Computes state variables m, h, and n 
LOCAL minf,hinf,ninf,pinf,qinf,mtau,htau,ntau,ptau,qtau
        minf = boltz(v,-34.6-shift,6.0-sshift)
        hinf = boltz(v,-56.8-shift,-7.8)
        ninf = boltz(v,-25,12.0)
        pinf = boltz(v,-43.0,24.0)
        qinf = boltz(v,-qv,-qs)
        mtau = 1*boltz(v,-45.0,-1.5) - 1*boltz(v,-65.0,-0.5) +0.04
        htau = 3*56.0*boltz(v,-29.0,-4.5) - 3*56.0*boltz(v,-49.0,-2.0) +2.0
        ntau = 19.0/(1.0 + exp((v+ 39.0)/8.0)) - 0.0/(1.0 + exp((v+ 59.0)/20.0))+1.0
        ptau = 2.*exp(-(v+50)*(v+50)/550)+1.1
        qtau = 20.0
        m' = (minf-m)/mtau
        h' = (hinf-h)/htau
        n' = (ninf-n)/ntau
        p' = (pinf-p)/ptau
        q' = (qinf-q)/qtau
}
 
 
 
FUNCTION boltz(x,y,z) {
                boltz = 1/(1 + exp(-(x - y)/z))
}
 
UNITSON


Loading data, please wait...