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]
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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;
proc celldef() {
  topol()
  subsets()
  geom()
  biophys()
  geom_nseg()
diam_seg()
}

create soma, dend1[3], dend1_1[3], dend2[5], SDI, SIprox, SIdistal
create axon

proc topol() { local i
  connect dend1(0), soma(0)
  for i = 1, 2 connect dend1[i](0), dend1[i-1](1)
  for i = 0, 2 connect dend1_1[i](0), soma(1)
  for i = 0, 1 connect dend2[i](0), dend1(1)
  for i = 2, 3 connect dend2[i](0), dend1[1](1)
  connect dend2[4](0), dend1[2](1)
  connect SDI(0), dend1[2](1)
  connect SIprox(0), SDI(1)
  connect SIdistal(0), SIprox(1)
  connect axon(0), SIdistal(1)
  basic_shape()
}
proc basic_shape() {
  soma {pt3dclear() pt3dadd(0, 0, 0, 1) pt3dadd(15, 0, 0, 1)}
  dend1 {pt3dclear() pt3dadd(0, 0, 0, 1) pt3dadd(-29, 0, 0, 1)}
  dend1[1] {pt3dclear() pt3dadd(-29, 0, 0, 1) pt3dadd(-59, 0, 0, 1)}
  dend1[2] {pt3dclear() pt3dadd(-59, 0, 0, 1) pt3dadd(-104, 0, 0, 1)}
  dend1_1 {pt3dclear() pt3dadd(15, 0, 0, 1) pt3dadd(90, -59, 0, 1)}
  dend1_1[1] {pt3dclear() pt3dadd(15, 0, 0, 1) pt3dadd(120, 0, 0, 1)}
  dend1_1[2] {pt3dclear() pt3dadd(15, 0, 0, 1) pt3dadd(105, 60, 0, 1)}
  dend2 {pt3dclear() pt3dadd(-29, 0, 0, 1) pt3dadd(-29, 60, 0, 1)}
  dend2[1] {pt3dclear() pt3dadd(-29, 0, 0, 1) pt3dadd(-29, -59, 0, 1)}
  dend2[2] {pt3dclear() pt3dadd(-59, 0, 0, 1) pt3dadd(-59, 60, 0, 1)}
  dend2[3] {pt3dclear() pt3dadd(-59, 0, 0, 1) pt3dadd(-59, -59, 0, 1)}
  SDI {pt3dclear() pt3dadd(-104, 0, 0, 1) pt3dadd(-119, 15, 0, 1)}
  SIprox {pt3dclear() pt3dadd(-119, 15, 0, 1) pt3dadd(-134, 30, 0, 1)}
  SIdistal {pt3dclear() pt3dadd(-134, 30, 0, 1) pt3dadd(-164, 60, 0, 1)}
  axon {pt3dclear() pt3dadd(-164, 60, 0, 1) pt3dadd(-194, 165, 0, 1)}
  dend2[4] {pt3dclear() pt3dadd(-104, 0, 0, 1) pt3dadd(-164, -44, 0, 1)}
}

objref all, Secdend
proc subsets() { local i
  objref all, Secdend
  all = new SectionList()
  Secdend = new SectionList()
  
    soma all.append()
    for i=0, 2 dend1[i] all.append()
    for i=0, 2 dend1_1[i] all.append()
    for i=0, 4 dend2[i] all.append()
    SDI all.append()
    SIprox all.append()
    SIdistal all.append()
    axon all.append()
	for i=0, 4 dend2[i] Secdend.append()

}
proc geom() {
  forsec all {  }
   soma.L = 20
   dend1.L = 6
   dend1[1].L = 7
   dend1[2].L = 6
   dend1_1.L = 500
   dend1_1[1].L = 500
   dend1_1[2].L = 500
    dend2.L = 500
   dend2[1].L =0.00001
   dend2[2].L = 0.00001
   dend2[3].L = 0.00001
   dend2[4].L = 500 //axonal
   SDI.L = 21
   SIprox.L = 15
   SIdistal.L = 15
   axon.L = 800
   
  
  
}
proc geom_nseg() {
  forsec all { nseg = int((L/(0.1*lambda_f(1000))+.999)/2)*2 + 1 }
}

proc diam_seg() {
 soma.diam = 20
   dend1.diam = 3.3
   dend1[1].diam = 2.75
   dend1[2].diam = 2.4
   dend1_1.diam(0:1) = 3:0.5
   dend1_1[1].diam(0:1) = 3:0.5
   dend1_1[2].diam(0:1) = 3:0.5
   dend2.diam(0:1) = 2 : 0.5
   dend2[1].diam(0:1) = 2 : 0.5
   dend2[2].diam(0:1) = 2 : 0.5
   dend2[3].diam(0:1) = 2 : 0.5
    dend2[4].diam(0:1) = 2:0.5
   SDI.diam = 1.5
   SIprox.diam = 1.15
   SIdistal.diam = 1
   axon.diam = 0.7
   
}


proc biophys() {
  forsec all {
    Ra = 150
    cm = 0.75

  }
  hhN=75 // for Ina and *2 for kdrDA (homo)
CaN = 1// for Ica and *x for kca (homo)
KCA= 0.1
hhsec = 75 // for Ina and *2 for kdrDA (secondary dendrites : hetero)
Casec =1// for Ica and *x (secondary dendrites : hetero)
KCAsec= 0.1

hhABD =75 // for Ina and *2 for kdrDA (ABD : hetero)
CaABD = 1// for Ica and *x (ABD: hetero)
KCAABD =0.1

  
  soma {
    insert Na12
      gbar_Na12 = hhN
   insert kdrDA
      gbar_kdrDA = hhN*2 
    insert pasnts
      g_pasnts = 1e-05
      e_pasnts = -50
insert kaDasoma
gbar_kaDasoma = 150
insert Ih
gbar_Ih = 3
insert CAV13
gbar_CAV13 = CaN
insert cad
insert kca
gbar_kca = KCA


ena=60
ek=-90
  }
  dend1 {
    insert Na12
      gbar_Na12 = hhN
insert kdrDA
      gbar_kdrDA = hhN*2
   insert pasnts
      g_pasnts = 1e-05
      e_pasnts = -50
insert kaDa
gbar_kaDa = 100
insert Ih
gbar_Ih = 3
insert CAV13
gbar_CAV13 = CaABD
insert cad
insert kca
gbar_kca = KCAABD

ena=60
ek=-90
  }
  dend1[1] {
    insert Na12
      gbar_Na12 = hhN
   insert kdrDA
      gbar_kdrDA = hhN*2
    insert pasnts
      g_pasnts = 1e-05
      e_pasnts = -50
 insert kaDa
gbar_kaDa = 100
insert Ih
gbar_Ih = 3
insert CAV13
gbar_CAV13 = CaABD
insert cad
insert kca
gbar_kca = KCAABD

ena=60
ek=-90
  }
  dend1[2] {
    insert Na12
      gbar_Na12 = hhN
    insert kdrDA
      gbar_kdrDA = hhN*2
    insert pasnts
      g_pasnts = 1e-05
      e_pasnts = -50
insert kaDa
gbar_kaDa = 100
insert Ih
gbar_Ih = 3
insert CAV13
gbar_CAV13 = CaABD
insert cad
insert kca
gbar_kca = KCAABD

ena=60
ek=-90
  }
  dend1_1 {
    insert pasnts
      g_pasnts = 1e-05
      e_pasnts = -50
    insert Na12
      gbar_Na12 = hhN
    insert kdrDA
      gbar_kdrDA = hhN*2
insert kaDa
gbar_kaDa = 100
insert Ih
gbar_Ih = 3
insert CAV13
gbar_CAV13 = CaABD
insert cad
insert kca
gbar_kca = KCAABD

ena=60
ek=-90
  }
  dend1_1[1] {
    insert Na12
      gbar_Na12 = hhN
    insert kdrDA
      gbar_kdrDA = hhN*2
    insert pasnts
      g_pasnts = 1e-05
      e_pasnts = -50
insert kaDa
gbar_kaDa = 100
insert Ih
gbar_Ih = 3
insert CAV13
gbar_CAV13 = CaABD
insert cad
insert kca
gbar_kca = KCAABD

ena=60
ek=-90
  }
  dend1_1[2] {
    insert pasnts
      g_pasnts = 1e-05
      e_pasnts = -50
    insert kdrDA
      gbar_kdrDA = hhN*2
    insert Na12
      gbar_Na12 = hhN
insert kaDa
gbar_kaDa = 100
insert Ih
gbar_Ih = 3
insert CAV13
gbar_CAV13 = CaABD
insert cad
insert kca
gbar_kca = KCAABD

ena=60
ek=-90
  }
  dend2 {
    insert pasnts
      g_pasnts = 1e-05
      e_pasnts = -50
    insert Na12
      gbar_Na12 = hhN
    insert kdrDA
      gbar_kdrDA = hhN*2
 insert kaDa
gbar_kaDa = 100
insert Ih
gbar_Ih = 3
insert CAV13
gbar_CAV13 = CaABD
insert cad
insert kca
gbar_kca = KCAABD

ena=60
ek=-90
  }
  dend2[1] {
    insert pasnts
      g_pasnts = 1e-05
      e_pasnts = -50
    insert kdrDA
      gbar_kdrDA = hhN*2
    insert Na12
      gbar_Na12 = hhN
 insert kaDa
gbar_kaDa = 100
insert Ih
gbar_Ih = 3
insert CAV13
gbar_CAV13 = CaABD
insert cad
insert kca
gbar_kca = KCAABD

ena=60
ek=-90
  }
  dend2[2] {
    insert pasnts
      g_pasnts = 1e-05
      e_pasnts = -50
    insert Na12
      gbar_Na12 = hhN
    insert kdrDA
      gbar_kdrDA = hhN*2
insert kaDa
gbar_kaDa = 100
insert Ih
gbar_Ih = 3
insert CAV13
gbar_CAV13 = CaABD
insert cad
insert kca
gbar_kca = KCAABD

ena=60
ek=-90
  }
  dend2[3] {
    insert pasnts
      g_pasnts = 1e-05
      e_pasnts = -50
    insert kdrDA
      gbar_kdrDA = hhN*2
    insert Na12
      gbar_Na12 = hhN
insert kaDa
gbar_kaDa = 100
insert Ih
gbar_Ih = 3
insert CAV13
gbar_CAV13 = CaABD
insert cad
insert kca
gbar_kca = KCAABD

ena=60
ek=-90
  }
   dend2[4] {
    insert pasnts
      g_pasnts = 1e-05
      e_pasnts = -50
    insert Na12
      gbar_Na12 = hhN
    insert kdrDA
      gbar_kdrDA = hhN*2
insert kaDa
gbar_kaDa = 100
insert Ih
gbar_Ih = 3
insert CAV13
gbar_CAV13 = CaABD
insert cad
insert kca
gbar_kca = KCAABD

ena=60
ek=-90
  }
  SDI {
insert pasnts
      g_pasnts = 1e-05
      e_pasnts = -50
        insert Na12
      gbar_Na12 = hhN
  insert kdrDA
      gbar_kdrDA = hhN*2
	  insert kaDa
gbar_kaDa = 100
insert Ih
gbar_Ih = 3
insert CAV13
gbar_CAV13 = CaABD
insert cad
insert kca
gbar_kca = KCAABD

ena=60
ek=-90
  }
  SIprox {
insert pasnts
      g_pasnts = 1e-05
      e_pasnts = -50
      insert Na12
      gbar_Na12 = 2000
	  
    insert kdrDA
      gbar_kdrDA = 1000

ena=60
ek=-90
  }
  SIdistal {
insert pasnts
      g_pasnts = 1e-05
      e_pasnts = -50
       insert Na12
      gbar_Na12 = 2000
	   
        insert kdrDA
      gbar_kdrDA =1000
ena=60
ek=-90
  }
  axon {
    insert Na12
      gbar_Na12 = 400
	   
    insert kdrDA
      gbar_kdrDA = 400
    insert pasnts
      g_pasnts = 1e-05
      e_pasnts = -50
ena=60
ek=-90
  }
}