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

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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;
load_file("dopaminergic.hoc")


load_file("fixnseg.hoc")

v_init = -62.6

clamp = 0                     /* switch for voltage clamp*/

tstart = 0
tstop = 500    /*time in msec*/

Dtmax = 1.0  
Dt = 1.00

dt = 5e-1 /*5e-4*/  

nainit=  4.075
vsolder=v_init
vsold=v_init

/*PARAMETERS*/
na_cond_s = 550.0e-6 
na_cond_d = 550.0e-6 
kdr_cond = 665.0e-6 
ca_cond = 11.196e-6
kca_cond = 0.20*59.0e-6  /* 0.20 change from Kuznetsova */
a_cond_s = 570.e-6     
a_cond_p = 285.0e-6 
a_cond_d = 266e-6   
/*stronger gA *1.28 =  729.6, 364.8, 340.48*/
iapl = 0 /*in nA, -0.180nA=-180pA*/

global_ra = 100   /* change from Kuznetsova */    
forall Ra = global_ra
global_cm = 0.75
forall cm = global_cm
g_celsius = 35
celsius = g_celsius
forall ion_style("na_ion", 2,2,0,0,0)
access soma			/* All default references are to soma */

objectvar vc
objref cvode
cvode = new CVode(1) /* 0 for clamp*/
x= cvode.active(1)

ourgampa=0.0
ourPnmda=0.0




proc init_cell() {


forsec  somatic {
	{insert nabalan}
        {insert hh3 gnabar_hh3 = na_cond_s gkhhbar_hh3 = kdr_cond gkabar_hh3 = a_cond_s
          qs_hh3 = 8.0 qv_hh3 = 56.0}
        {insert pump}
        {insert leak}
        {insert cabalan}
        {insert cachan gcalbar_cachan = ca_cond gkbar_cachan = 0.0}
        {insert kca gkbar_kca = kca_cond}
        // {insert capump} 

    }


forsec  basal {
	
	{insert nabalan}
	{insert hh3 gnabar_hh3 = na_cond_d  gkhhbar_hh3 = kdr_cond gkabar_hh3 = a_cond_d
          qv_hh3 = 60.0 qs_hh3 = 5.0}
	{insert pump}
        {insert leak}       
        {insert cabalan}
        {insert cachan gcalbar_cachan = ca_cond gkbar_cachan = 0.0 }
        {insert kca gkbar_kca = kca_cond}
        
	}

forsec excitozone {
        
	{insert nabalan}
	{insert hh3 gnabar_hh3 = 50*na_cond_s  gkhhbar_hh3 = 30*kdr_cond gkabar_hh3 = a_cond_d
          qv_hh3 = 60.0 qs_hh3 = 5.0 shift_hh3 = 5 sshift_hh3 = -4}
	{insert pump}
        {insert leak}       
        {insert cabalan}
        {insert cachan gcalbar_cachan = ca_cond gkbar_cachan = 0.0 }
        {insert kca gkbar_kca = kca_cond}

        }

forsec axonal {
	
	{insert nabalan}
	{insert hh3 gnabar_hh3 = na_cond_d  gkhhbar_hh3 = kdr_cond gkabar_hh3 = a_cond_d
          qv_hh3 = 60.0 qs_hh3 = 5.0}
	{insert pump}
        {insert leak}       
        {insert cabalan}
        {insert cachan gcalbar_cachan = ca_cond gkbar_cachan = 0.0 }
        {insert kca gkbar_kca = kca_cond}

        }   

forall cm = global_cm
forall Ra = global_ra
g_celsius = 35

    }
tot=0
forall {tot=tot+nseg}
print "segments before ", tot
nseg=1

// Increase number of segments
geom_nseg()
tot=0
forall {tot=tot+nseg}
print "segments after ", tot

init_cell()

load_file("sesion.ses")

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