Regulation of the firing pattern in dopamine neurons (Komendantov et al 2004)

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Accession:83547
Midbrain dopaminergic (DA) neurons in vivo exhibit two major firing patterns: single-spike firing and burst firing. The firing pattern expressed is dependent on both the intrinsic properties of the neurons and their excitatory and inhibitory synaptic inputs. Experimental data suggest that the activation of NMDA and GABAA receptors is crucial contributor to the initiation and suppression of burst firing, respectively, and that blocking calcium-activated potassium channels can facilitate burst firing. This multi-compartmental model of a DA neuron with a branching structure was developed and calibrated based on in vitro experimental data to explore the effects of different levels of activation of NMDA and GABAA receptors as well as the modulation of the SK current on the firing activity.
Reference:
1 . Komendantov AO, Komendantova OG, Johnson SW, Canavier CC (2004) A modeling study suggests complementary roles for GABAA and NMDA receptors and the SK channel in regulating the firing pattern in midbrain dopamine neurons. J Neurophysiol 91:346-57 [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Electrogenic pump;
Brain Region(s)/Organism:
Cell Type(s): Substantia nigra pars compacta DA cell;
Channel(s): I A; I K; I K,Ca; I Sodium; I Calcium; Na/K pump;
Gap Junctions:
Receptor(s): GabaA; NMDA;
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Activity Patterns; Bursting; Detailed Neuronal Models; Sodium pump;
Implementer(s): Kuznetsova, Anna [anna.kuznetsova at utsa.edu];
Search NeuronDB for information about:  Substantia nigra pars compacta DA cell; GabaA; NMDA; I A; I K; I K,Ca; I Sodium; I Calcium; Na/K pump;
/* Driver Program for Midbrain Dopaminergic Neuron model */

/* The following command loads the standard run library functions into
 * the simulator.  These library functions are used to initialize the
 * simulator, begin and end simulations, and plot variables during a
 * simulation. */
timecon = 0
back= 0                         /* 1 switch for running in the background */
sakmann=0
if(!back)load_file("nrngui.hoc")
verbose=0
v_init = -60
vcseries = 0
clamp = 0                     /* switch for voltage clamp*/
restart = 0                      /* switch for initializing from state.old */
tstart = 0
if(vcseries) tstop = 800 else tstop = 10000
if(clamp && !vcseries) tstop= 600
/*if(timecon) tstop = 100*/
if(timecon) tstop = 800
nsyn = 1			/* The number of synapses */
soma_len= 25.0 /*25*/
soma_diam= 15.0
ndend=4
nbranch=2
dend_diam= 1.5  /* 1.5 need to make dendrite taper */
prox_diam= 3.0  /* 3.0 need to make dendrite taper */
taper = 1.0
dend_len = 500.0
prox_len = 150.0
Dtmax =   1.0  
Dt =   1.00
if(timecon) Dtmax = 1.0 
dt = 5e-4  /*0.1 5e-9 */
if(timecon) dt = 0.01
nainit=  4.000
vsolder=v_init
vdolder=v_init
vsold=v_init
vdold=v_init

create dummy,soma, prox[ndend], dend[nbranch*ndend]	/* Create all of the cell's sections */
global_ra = 400
forall Ra = global_ra
global_cm = 1.0
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 syn[nsyn]		/* Declare the object variables for
				 * the three synapses */
objectvar stim
objectvar vc
objref cvode
cvode = new CVode(1) /* 0 for clamp*/
x= cvode.active(1)

proc init_cell() {
/* First set all of the dimensions and insert the channels into each
 * section. */
    dummy{
      L=1
      d=1
    }
    soma {
	nseg = 1		/* # of compartments */
	diam = soma_diam		/* Set the diameter of the soma (in um) */
	L = soma_len			/* Set the length of the soma (in um) */
        
	{insert nadifl D_nadifl = 0.60 nainit_nadifl = 2.4 f_nadifl = 4.0}
        {insert hh3 gnabar_hh3 = 5500.0e-6 gkabar_hh3 = 100.0e-6 gkhhbar_hh3 = 1000.0e-6
          miv_hh3 = 44.6 htv1_hh3 = 39.0 hiv_hh3 = 66.8 htv2_hh3 = 59.0}
        {insert pump ipumpmax_pump = 0.0036 km_pump = 10.0  }
        {insert leak gkbar_leak = 18.0e-6  gnabar_leak = 9.5e-6  
          ggabaa_leak = 350.0e-6 gcabar_leak = 0.6e-6 }
        /*{insert cadifus TotalBuffer_cadifus = 0.300 cainit_cadifus = 0.000057 }*/
        {insert cadifus fCa_cadifus = 0.005 cainit_cadifus = 0.000116 }
       {insert calcha gcatbar_calcha = 1044.0e-6 gcanbar_calcha = 171.0e-6 
          gcalbar_calcha = 216.0e-6 gcahvabar_calcha = 0.0e-6}
        {insert gkca gkbar_gkca = 0.0e-6 ek_gkca = -100 km_gkca = 0.00019
          n_gkca = 4.0}
        {insert capump icapumpmax_capump = 0.0312 km_capump = 0.0005}
        /*{insert gaba ggabaa_gaba = 350.0e-6 ecl_gaba = -70.0}*/
if (!clamp) {
        istim = 0.0 /* 0.015 nA=15pA   0.07 nA=70pA*/
        stim = new MyIClamp(.5)
        {stim.del = 0 stim.dur = 200000 stim.amp = -0.180
        /* stim.amp = istim*3.1416*diam*L*(0.01) */
         stim.amp2 = 0}
if(timecon) stim.dur = 600  /*(ms)*/
if (sakmann) stim.amp2 = -0.050
if(timecon) stim.amp2 = -0.020 
if(timecon) stim.del = 100
     } else {
	vc = new SEClamp(.5)
        if(!vcseries) vc.amp1 = -60.0 else vc.amp1 = -130
	vc.dur1 =  50
	vc.amp2 = -30.0
	vc.dur2 = 350
	vc.amp3 = -60.0
	vc.dur3 = 201
    }

	pt3dclear()
	pt3dadd(0,0,0,soma_diam)
	pt3dadd(soma_len,0,0,soma_diam)

    }
 
    for i = 0, ndend-1 prox[i] {
	nseg = 1	/* # of compartments */
	L = prox_len			/* Set the length of the dendrite (in um) */
     
	{insert nadifl D_nadifl = 0.60  nainit_nadifl = 3.0  f_nadifl = 1.0}
	{insert hh3 gnabar_hh3 = 5500.0e-6 gkabar_hh3 = 300.0e-6 gkhhbar_hh3 = 1000.0e-6
          miv_hh3 = 34.6 htv1_hh3 = 29.0 hiv_hh3 = 56.8 htv2_hh3 = 49.0}
	{insert pump ipumpmax_pump = 0.0072  km_pump = 10.0}
	{insert leak gkbar_leak = 18.0e-6 gnabar_leak = 9.5e-6 
          ggabaa_leak = 35.0e-6 gcabar_leak = 0.0e-6 }
      /*{insert cadifus cainit_cadifus = 0.000050 }
        {insert calcha gcatbar_calcha = 0 gcanbar_calcha = 2.8e-6 
          gcalbar_calcha = 3.6e-6 gcahvabar_calcha = 6.2e-6}
        {insert gkca gkbar_gkca = 0.0000 km_gkca = 0.00030 slope_gkca  = 0.00003}
        {insert capump icapumpmax_capump = 0.00036 km_capump = 0.0005}*/
	/*{insert gaba ggabaa_gaba = 35.0e-6 ecl_gaba = -70.0}*/       
        {insert nmda Pbar_nmda = 0.75e-6  /*0.23e-6*10.503/2.2237=1.086e-6 2.2237=IEI 
				Multiply both Pnmda and gampa when changing intensity*/ 
	   }
        {insert ampa gampa_ampa = 0.0e-6 /*2.68e-6*3.626/2.2237*/ 
          gampak_ampa = 0.0e-6 ek_ampa = -100.0 ratio = 1}
          
forall cm = global_cm
forall Ra = global_ra
g_celsius = 35
    }
 
    for i = 0, nbranch*ndend - 1 dend[i] {
	nseg = 1	/* # of compartments */
	L = dend_len - prox_len 			/* Set the length of the dendrite (in um) */
        
	{insert nadifl D_nadifl = 0.60 nainit_nadifl = 4.59 f_nadifl = 1.0}
	{insert hh3 gnabar_hh3 = 5500.0e-6 gkabar_hh3 = 1000.0e-6 gkhhbar_hh3 = 1000e-6
           miv_hh3 = 26.6 htv1_hh3 = 21 hiv_hh3 = 48.8 htv2_hh3 = 41.0}
        {insert pump ipumpmax_pump = 0.009  km_pump = 10.0}
        {insert leak gkbar_leak = 18.0e-6 gnabar_leak = 9.5e-6  
           ggabaa_leak = 35.0e-6 gcabar_leak = 0.0e-6 }
      /*{insert cadifus cainit_cadifus = 0.000263}
        {insert calcha gcatbar_calcha = 0 gcanbar_calcha = 2.8e-6 
           gcalbar_calcha = 3.6e-6 gcahvabar_calcha = 6.2e-6}
        {insert gkca gkbar_gkca = 0.00002 km_gkca = 0.00025 slope_gkca = 0.00003}
        {insert capump icapumpmax_capump = 0.00288 km_capump = 0.0005}*/
        /*{insert gaba ggabaa_gaba = 35.0e-6 ecl_gaba = -70.0}*/
	{insert nmda Pbar_nmda = 0.75e-6 /*0.23e-6*10.503/2.2237=1.086e-6 */
           }
	{insert ampa  gampa_ampa = 0.0e-6 /*2.68e-6*3.626/2.2237*/ 
	   gampak_ampa = 0.0e-6 ek_ampa = -100.0}
    

forall cm = global_cm
forall Ra = global_ra
g_celsius = 35
    }

/* Next we construct the topology by connecting each of the sections
 * together. */
    connect soma(0),dummy(1)
    connect prox[0](0),soma(0)
    connect prox[1](0), soma(1)
    connect prox[2](0), soma(0.5)
    connect prox[3](0), soma(0.5) 
    for j = 0, ndend-1 {
    for i = 0, nbranch-1 {
    connect dend[j+i*ndend](0), prox[j](1)}}

        dummy{
	pt3dclear()
	pt3dadd(0.5*soma_len,0,1,1)
	pt3dadd(0.5*soma_len,0,0,1)
               }
        prox[0]{
	pt3dclear() 
	pt3dadd(0,0,0,prox_diam)
	pt3dadd(-prox_len,0,0,prox_diam)
               }
        dend[0]{
	pt3dclear() 
	pt3dadd(-prox_len,0,0,dend_diam)
	pt3dadd(-dend_len,0,0,dend_diam/taper)
               }
        if(nbranch==2) dend[4]{
	pt3dclear() 
	pt3dadd(-prox_len,0,0,dend_diam)
	pt3dadd(-prox_len,dend_len-prox_len,0,dend_diam/taper)
               }
        prox[1]{
	pt3dclear() 
	pt3dadd(soma_len,0,0,prox_diam)
	pt3dadd(soma_len+prox_len,0,0,prox_diam)
               }
        dend[1]{
	pt3dclear() 
	pt3dadd(soma_len+prox_len,0,0,dend_diam)
	pt3dadd(soma_len+dend_len,0,0,dend_diam/taper)
               }
        if(nbranch==2) dend[5]{
	pt3dclear() 
	pt3dadd(soma_len+prox_len,0,0,dend_diam)
	pt3dadd(soma_len+prox_len,prox_len-dend_len,0,dend_diam/taper)
               }
        prox[2]{
	pt3dclear() 
	pt3dadd(0,soma_diam/2,0,prox_diam)
	pt3dadd(0,(soma_diam/2 + prox_len),0,prox_diam)
               }
        dend[2]{
	pt3dclear() 
	pt3dadd(0,(soma_diam/2 + prox_len),0,dend_diam)
	pt3dadd(0,soma_diam/2 + dend_len,0,dend_diam/taper)
               }
        if(nbranch==2) dend[6]{
	pt3dclear() 
	pt3dadd(0,(soma_diam/2 + prox_len),0,dend_diam)
	pt3dadd(dend_len-prox_len,soma_diam/2 + prox_len,0,dend_diam/taper)
               }
        prox[3]{
	pt3dclear() 
	pt3dadd(0,-soma_diam/2,0,prox_diam)
	pt3dadd(0,(-soma_diam/2 - prox_len),0,prox_diam)
               }
        dend[3]{
	pt3dclear() 
	pt3dadd(0,-soma_diam/2 - prox_len,0,dend_diam)
	pt3dadd(0,-soma_diam/2 - dend_len,0,dend_diam/taper)
               }
        if(nbranch==2) dend[7]{
	pt3dclear() 
	pt3dadd(0,-soma_diam/2 - prox_len,0,dend_diam)
	pt3dadd(prox_len-dend_len,-soma_diam/2 - prox_len,0,dend_diam/taper)
               }
}


topology()

init_cell()			/* Call the function to initialize our
				 * cell. */
objref ss,f1,f2
ss = new SaveState()
f1 = new File()
f2 = new File()



proc init() {local i
if(!restart){
             finitialize(v_init)
             fcurrent()
             }
if(restart){ 
           f1.ropen("state.old")
           ss.fread(f1)
           f1.close
           finitialize(v_init)
           ss.restore()
           t=tstart
           if(cvode.active()){
           cvode.re_init()

} else {
           fcurrent()
        }
 frecord_init()
           }
        t = tstart
}




/*proc continuerun() {local rt
	eventcount=0
	eventslow=1
	stoprun = 0
        startsw()
	while(t < $1 && stoprun == 0) {
		step()
		rt = stopsw()
		if (rt > realtime) {
			realtime = rt
			fastflushPlot()
			doNotify()
			if (realtime == 2 && eventcount > 50) {
				eventslow = int(eventcount/50) + 1
			}
			eventcount = 0
		}else{
			eventcount = eventcount + 1
			if ((eventcount%eventslow) == 0) {
				doEvents()
			}
		}
	}
f2.wopen("state.new")
ss.save()
ss.fwrite(f2)
f2.close
flushPlot()
}*/
init()
/*startsw()
flushPlot()*/
if(back){
if(!clamp ||verbose) {print t,soma.v(0.5),dend[1].v(0.99),soma.nai(0.5), dend[1].nai(0.99),soma.cai(0.5),dend[1].inapump_pump(0.99), dend[1].inmda_nmda(0.99)}
if(clamp && !vcseries && !verbose) print t,vc.i,soma.cai(0.5),soma.v(0.5)
if(vcseries) j= 10 else j = 0
for i = 0, j { if (vcseries) vc.amp1 = vc.amp1 + 10}
if(vcseries) init()
next = t + Dt
flag1=0
flag2=0
hold = 0
while (t<tstop){
          vsolder=vsold
          vdolder=vdold
          vsold=soma.v(0.5)
          vdold=dend[1].v(0.99)
          fadvance()
           if(!clamp||verbose){
          if((vsolder<vsold &&soma.v(0.5) <vsold)||(vsolder>vsold && soma.v(0.5)>vsold)||(vdolder<vdold &&dend[1].v(0.99) <vdold)|| (vdolder>vdold && dend[1].v(0.99)>vdold)) {
          vsolder=soma.v(0.5)
          vdolder=dend[1].v(0.99)
                           print t,soma.v(0.5),dend[1].v(0.99),soma.nai(0.5), dend[1].nai(0.99),soma.cai(0.5), dend[1].inapump_pump(0.99),dend[1].inmda_nmda(0.99)
               next = t + Dt
                           flag2=1
                           hold=dt
          soma.v(0.5)=vsolder
          dend[1].v(0.99)=vdolder
                            }
                            }   
               if(t>=next){
               Dt = 100*dt
               if(Dt>Dtmax) Dt = Dtmax
               if (Dt<.1) Dt = .1
               next = t + Dt
         if(!clamp||verbose) print t,soma.v(0.5),dend[1].v(0.99),soma.nai(0.5), dend[1].nai(0.99),soma.cai(0.5), dend[1].inapump_pump(0.99),dend[1].inmda_nmda(0.99)
if(clamp && !vcseries && !verbose) print t,vc.i,soma.cai(0.5),soma.v(0.5)
                          }
                 }
if(vcseries) print vc.amp1,vc.i
f2.wopen("state.new")
ss.save()
ss.fwrite(f2)
f2.close
} else{ if(clamp) {xopen("clamp.ses")} else {xopen("new.ses")}
                   forall Ra = global_ra
                   forall cm = global_cm
                   prox{ forall cm = global_cm}
                   dend{ forall cm = global_cm}
                   celsius = g_celsius
       }