Dopaminergic subtantia nigra neuron (Moubarak et al 2019)

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Accession:245427
Axon initial segment (AIS) geometry critically influences neuronal excitability. Interestingly, the axon of substantia nigra pars compacta (SNc) dopaminergic (DA) neurons displays a highly variable location and most often arises from an axon-bearing dendrite (ABD). We combined current-clamp somatic and dendritic recordings, outside-out recordings of dendritic sodium and potassium currents, morphological reconstructions and multi-compartment modelling to determine cell-to-cell variations in AIS and ABD geometry and their influence on neuronal output (spontaneous pacemaking frequency, AP shape). Both AIS and ABD geometries are highly variable between SNc DA neurons. Surprisingly, we found that AP shape and pacemaking frequency were independent of AIS geometry. Modelling realistic morphological and biophysical variations clarify this result: in SNc DA neurons, the complexity of the ABD combined with its excitability predominantly define pacemaking frequency and AP shape, such that large variations in AIS geometry negligibly affect neuronal output, and are tolerated.
Reference:
1 . Moubarak E, Engel D, Dufour MA, Tapia M, Tell F, Goaillard JM (2019) Robustness to Axon Initial Segment Variation Is Explained by Somatodendritic Excitability in Rat Substantia Nigra Dopaminergic Neurons. J Neurosci 39:5044-5063 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type:
Brain Region(s)/Organism: Basal ganglia;
Cell Type(s): Substantia nigra pars compacta DA cell;
Channel(s): Ca pump; I A; I Calcium; I h; I Na,t; I K;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Action Potential Initiation; Pacemaking mechanism;
Implementer(s): Tell, Fabien [fabien.tell at univ-amu.fr]; Moubarak, Estelle ;
Search NeuronDB for information about:  Substantia nigra pars compacta DA cell; I Na,t; I A; I K; I h; I Calcium; Ca pump;
COMMENT 

Model for an SODIUM cuRrent recorded in DA neurons.Nav12 style

Activation and inactivation parameters DERIVED FROM MIGLIORE 


ENDCOMMENT


NEURON
 {
	 THREADSAFE
  SUFFIX Na12  USEION na READ ena WRITE ina 
 
RANGE gbar, g, i  

RANGE atau, btau   

RANGE ainf, binf 



 }

UNITS {

(pS) =(picosiemens)
(mV) = (millivolt)
(mA) = (milliamp)

}

PARAMETER { 
  gbar = 50 (pS/microm2)
  Vmid_ac = -28(mV)    : actually corresponds to -20 mV because the m^3 model is rightward shifted
  k_ac = 7.7(mV) 	: corresponds to 7
  k_ina = -10 (mV)
Vmid_ina = -50 (mV)
  
  m=3         
  h=1        : gate parameters according to the HH formalism (m*m*m*h)
celsius = 32 (degC)
q10=1.5

}

 ASSIGNED {
  v	(mV)
  ina 	(mA/cm2)
  i 	(mA/cm2)
  g	(pS/microm2)
  atau (ms)
  btau (ms)
    ainf (1)
  binf (1)
 ena (mV)
 }


STATE {a b}

BREAKPOINT {
  SOLVE states METHOD cnexp

 

  g = (gbar*(a^m)*(b^h)) 
  i = (0.0001)*g*(v-ena)
  ina = i
}

INITIAL {

rates(v)
a= ainf
b=binf


}

DERIVATIVE states {
 rates(v)
  a' = (ainf-a)/atau
  b' = (binf-b)/btau
 
}


FUNCTION a_inf (V (mV)) () {

  a_inf = 1/(1+exp(-(V-Vmid_ac)/k_ac))  : activation system (a*a*a)
}

FUNCTION b_inf (V (mV)) () {
  b_inf = 1/(1+exp(-(V-Vmid_ina)/k_ina)) : inactivation system (b)
}

FUNCTION a_tau (V (mV)) (ms) {
UNITSOFF

a_tau= 0.01+(0.33/(1+((V+20)/30)^2))
: time constant of activation depends on V 

UNITSON
}

FUNCTION b_tau (V (mV)) (ms) {

UNITSOFF

  b_tau = 0.7+(16/(1+((V+50)/8)^2))
 : fast inactivation  


UNITSON 


}



PROCEDURE rates(V (mV)) {
LOCAL qt
UNITSOFF
qt=q10^((celsius-24)/10)
UNITSON 
atau=a_tau(V)/qt

ainf=a_inf(V)

btau=b_tau(V)/qt

binf=b_inf(V)



}

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