/*Reproduces Fig.10B */

/* 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 = -69.953008
vcseries = 0
clamp = 0                     /* switch for voltage clamp*/
restart = 0                      /* switch for initializing from state.old */
tstart = 0
if(vcseries) tstop = 800 else tstop = 5000
if(clamp && !vcseries) tstop= 600
if(timecon) tstop = 800
nsyn = 1			/* The number of synapses */
soma_len= 25.0 
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  
if(timecon) dt = 0.01
nainit=  4.000
vsolder=v_init
vdolder=v_init
vsold=v_init
vdold=v_init
ourgampa=0.0
ourPnmda=0.0

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
objref ff
objref vec1,vec2
cvode = new CVode(1) /* 0 for clamp*/
x= cvode.active(1)
ff = new File()
vec1 = new Vector(900001)
ff.ropen("fig10AMPA.dat")
n = vec1.scanf(ff, 900000)
ff.close()
ff = new File()
vec2 = new Vector(900001)
ff.ropen("fig10NMDA.dat")
n = vec2.scanf(ff, 900000)
ff.close()
samplestep = 0.1
objref tvec1,tvec2
tvec1 = vec1.c.indgen(samplestep)
tvec2 = vec2.c.indgen(samplestep)
vec1.play(&ourgampa,tvec1,1)
vec2.play(&ourPnmda,tvec2,1)

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 nabalan nainit_nabalan = 5.8868235 f_nabalan = 4.0}
        {insert hh3 gkabar_hh3 = 100.0e-6
          miv_hh3 = 44.6 hiv_hh3 = 66.8 htv1_hh3 = 39.0 htv2_hh3 = 59.0}
        {insert pump ipumpmax_pump = 0.0036}
        {insert leak gcabar_leak = 0.6e-6 ggabaa_leak = 300.0e-6 /*when changing
         change the corresponding parameter in dend and prox with ratio g_prox=g_dend=g_soma/10 */}
        {insert cabalan cainit_cabalan = 0.00025269677 }
        {insert cachan}
        {insert kca gkbar_kca = 800.0e-6}
        {insert capump}
if (!clamp) {
        istim = 0.0
        stim = new MyIClamp(.5)
        {stim.del = 0 stim.dur = 200000 stim.amp = 0.0  /*in nA, -0.180nA=-180pA*/
         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 nabalan nainit_nabalan = 11.854643 f_nabalan = 1.0}
	{insert hh3 gkabar_hh3 = 300.0e-6
          miv_hh3 = 34.6 hiv_hh3 = 56.8 htv1_hh3 = 29.0 htv2_hh3 = 49.0}
	{insert pump ipumpmax_pump = 0.0072}
	{insert leak gcabar_leak = 0.0e-6 ggabaa_leak = 30.0e-6 }
        {insert nmda}
        {insert ampa ratio_ampa = 2}
          
forall cm = global_cm
forall Ra = global_ra
g_celsius = 35
    }
 
     for i = 0, ndend-1 prox[i] {
      prox[i] for (x,0) { 
        setpointer caisoma_nmda(x), soma.cai(0.5)
        setpointer nmdasyn_nmda(x), ourPnmda 
        setpointer ampasyn_ampa(x), ourgampa
	  }
        } 
         
      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 nabalan nainit_nabalan = 9.9269572 f_nabalan = 1.0}
	{insert hh3 gkabar_hh3 = 1000.0e-6
           miv_hh3 = 26.6 hiv_hh3 = 48.8 htv1_hh3 = 21 htv2_hh3 = 41.0}
        {insert pump ipumpmax_pump = 0.009}
        {insert leak gcabar_leak = 0.0e-6 ggabaa_leak = 30.0e-6 }
        {insert nmda}
	{insert ampa ratio_ampa = 2}
    
forall cm = global_cm
forall Ra = global_ra
g_celsius = 35
    }

   for i = 0, nbranch*ndend - 1 dend[i] {
      dend[i] for (x,0) { 
        setpointer caisoma_nmda(x), soma.cai(0.5)
        setpointer nmdasyn_nmda(x), ourPnmda
	setpointer ampasyn_ampa(x), ourgampa  
	  }
          }
   
 /* 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("state10b.old")
           ss.fread(f1)
           f1.close
           finitialize(v_init)
           ss.restore(1)
           t=tstart
           if(cvode.active()){
           cvode.re_init()

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

init()
if(back){
if(!clamp ||verbose) {print t,soma.v(0.5),soma.nai(0.5),prox.nai(0.5),dend.nai(0.5),soma.cai(0.5)}
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-dt){
          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),soma.nai(0.5),prox.nai(0.5),dend.nai(0.5),soma.cai(0.5)
               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),soma.nai(0.5),prox.nai(0.5),dend.nai(0.5),soma.cai(0.5)
if(clamp && !vcseries && !verbose) print t,vc.i,soma.cai(0.5),soma.v(0.5)
                          }
                 }
              print t,soma.v(0.5),soma.nai(0.5),prox.nai(0.5),dend.nai(0.5),soma.cai(0.5)
if(vcseries) print vc.amp1,vc.i
f2.wopen("state10b.new")
ss.save()
ss.fwrite(f2)
f2.close
} else{ if(clamp) {xopen("clamp.ses")} else {xopen("fig10b.ses")}
                   forall Ra = global_ra
                   forall cm = global_cm
                   prox{ forall cm = global_cm}
                   dend{ forall cm = global_cm}
                   celsius = g_celsius
       }