load_file("nrngui.hoc")
tstop=50
sim=14 // sim=49 in the paper; it was changed here to speed up simulations
nsyn=40
nfs=105
nrs=170
xopen("c20465.hoc")
rs_sil=0.0006
fs_sil=0.0006
MODELTYPE = 0
use_mcell_ran4(1)
lowindex = 1001
mcell_ran4_init(lowindex)
highindex = 1
print "---------------------------SIM running-----------------------------"
NMDAFLAG = 0
if (NMDAFLAG == 0) { //only AMPA-R
wtAmpa = 1
wtNmda = 0
} else { //NMDAFLAG = 1, with both AMPA-R, NMDA-R
wtAmpa = 0.8
wtNmda = 0.2
}
soma area(0.5)
TOTALDEND = APIDENDMAX + BASDENDMAX + 3 //"3": counting start at 0
objref dend[TOTALDEND],apc,rc,rd,fs,rs,rex,rob,rtrp,ror,rexfs,rexrs,pc,rci,h,u, Ens[3000], syn[3000], nc[3000],Ensi[3000], syni[3000], nci[3000],Ensii[3000], synii[3000], ncii[3000]
strdef dend2, trunk
index = 0
forsec "dendrite" { //this will includes both dendrites and apical-dendrites
dend[index] = new SectionRef()
index += 1
}
//quadratic function fitting result A and B are set in cell's hoc file
A = 0.0036
B = 156
//synapses rise and decay time constants from andrasfalvy mody
TAU1e=0.5
TAU2e=5.5
TAU1i=0.73
TAU2i=6.5
dist=1
rel=0.1
Rm = 28000 //unit: Ohm-cm^2
RmDend = Rm/1
RmSoma = Rm
RmAx = Rm
Cm = 1
CmSoma= Cm
CmAx = Cm
CmDend = Cm*1
RaAll= 50 //unit: Ohm-cm
RaSoma=50
RaAx = 50
Vrest = -65
gna = .02
AXONM = 2
gkdr = 0.01
celsius = 35.0
KMULT = 0.025
KMULTP = 0.025
ghd=0.00005
nash=0
forsec "axon" {insert pas e_pas=Vrest g_pas = 1/RmAx Ra=RaAx cm=CmAx}
forsec "soma" {
insert pas e_pas=Vrest g_pas = 1/RmSoma Ra=RaSoma cm=CmSoma
insert ds
}
forsec "dendrite" {insert pas e_pas=Vrest g_pas = 1/RmDend Ra=RaAll cm=CmDend}
forsec "user5" {insert pas e_pas=Vrest g_pas = 1/RmDend Ra=RaAll cm=CmDend}
access soma
freq=50
load_file("fixnseg.hoc")
geom_nseg()
tot=0
forall {tot=tot+nseg}
distance()
maxdist=0
forsec "user5" for(x) {if (distance(x)>maxdist) {maxdist=distance(x)}}
forsec "axon" {
insert nax gbar_nax=gna * AXONM sh_nax=nash
insert kdr gkdrbar_kdr=gkdr
insert kap gkabar_kap = KMULTP*0.2
}
forsec "soma" {
insert hd ghdbar_hd=ghd vhalfl_hd=-73
insert na3 ar_na3=1 sh_na3=nash gbar_na3=gna
insert kdr gkdrbar_kdr=gkdr
insert kap gkabar_kap = KMULTP
}
/*---------------------setting up apical oblique dendrite channel kinetics--------*/
for (i=0; i<= APIDENDMAX; i += 1) {
access apical_dendrite[i] {
insert ds
if (diam>0.35) {factor=1} else {factor=1}
insert hd ghdbar_hd=ghd
insert na3 ar_na3=1 gbar_na3=gna*factor sh_na3=nash
insert kdr gkdrbar_kdr=gkdr*factor
insert kap gkabar_kap=0
insert kad gkabar_kad=0
for (x) if (x>0 && x<1) { xdist = distance(x)
ghdbar_hd(x) = factor*ghd*(1+3*xdist/100)
if (xdist > 100){
vhalfl_hd=-81
gkabar_kad(x) = factor*KMULT*(1+xdist/100)
} else {
vhalfl_hd=-73
gkabar_kap(x) = factor*KMULTP*(1+xdist/100)
}
}
}
}
/*---------------------setting up basal dendrite channel kinetics--------*/
for (i=0; i <= BASDENDMAX; i += 1) {
access dendrite[i] {
if (diam>0.35) {factor=1} else {factor=1}
insert hd ghdbar_hd=ghd
insert na3 ar_na3=1 gbar_na3=gna*factor sh_na3=nash
insert kdr gkdrbar_kdr=gkdr*factor
insert kap gkabar_kap=0
insert kad gkabar_kad=0
for (x) if (x>0 && x<1) { xdist = distance(x)
ghdbar_hd(x) = factor*ghd*(1+3*xdist/100)
if (xdist > 100){
vhalfl_hd=-81
gkabar_kad(x) = factor*KMULT*(1+xdist/100)
} else {
vhalfl_hd=-73
gkabar_kap(x) = factor*KMULTP*(1+xdist/100)
}
}
}
}
/*----------------------------setting up main trunk channel kinetics-------------*/
forsec "user5" { // the main trunk
insert ds
insert hd ghdbar_hd=ghd
insert na3 ar_na3=1 gbar_na3=gna sh_na3=nash
insert kdr gkdrbar_kdr=gkdr
insert kap gkabar_kap=0
insert kad gkabar_kad=0
for (x) if (x>0 && x<1) { xdist = distance(x)
ghdbar_hd(x) = ghd*(1+3*xdist/100)
if (xdist > 100){
vhalfl_hd=-81
gkabar_kad(x) = KMULT*(1+xdist/100)
} else {
vhalfl_hd=-73
gkabar_kap(x) = KMULTP*(1+xdist/100)
}
}
}
// ---------------------- Graph ---------------------------------
h = new VBox()
h.intercept(1)
u = new Graph()
u.size(0, 700, 0, 1)
u.beginline()
xpanel("")
xpanel()
h.intercept(0)
h.map()
// ---------------------- End Graph ---------------------------------
access soma
proc init() {
t=0
forall {
v=Vrest
if (ismembrane("nax") || ismembrane("na3")) {ena=55}
if (ismembrane("kdr") || ismembrane("kap") || ismembrane("kad")) {ek=-90}
if (ismembrane("hd") ) {ehd_hd=-30}
}
finitialize(Vrest)
fcurrent()
forall {
for (x) {
if (ismembrane("na3")||ismembrane("nax")){e_pas(x)=v(x)+(ina(x)+ik(x))/g_pas(x)}
if (ismembrane("hd")) {e_pas(x)=e_pas(x)+i_hd(x)/g_pas(x)}
}
}
cvode.re_init()
cvode.event(tstop)
access soma
}
dt = 0.1
steps_per_ms = 1/dt
choice = 1
if (choice == 1 || choice == 2) {
BEGINSECTION= 0
ENDSECTION= TOTALDEND - 1
} else {
BEGINSECTION= 0
ENDSECTION= BASDENDMAX
}
rc = new Random()
rc.MCellRan4(highindex+1)
rc.uniform(BEGINSECTION, ENDSECTION)
rd = new Random()
rd.MCellRan4(highindex+2)
rd.uniform(0,1)
pc = new Random()//
pc.MCellRan4(highindex+6)
pc.normal(5,5)
fs = new Random() // basket
fs.MCellRan4(highindex+5)
fs.normal(2.5,0.85) // variance= SEM*sqrt(n) from scanziani sem=.2 n=18
rs = new Random()// bistratified
rs.MCellRan4(highindex+7)
rs.normal(4.2,1.75) // variance= SEM*sqrt(n) from scanziani sem=.3 n=34
rex = new Random()
rex.MCellRan4(highindex+8)
rex.uniform(0, 28858)
rexfs = new Random()
rexfs.MCellRan4(highindex+9)
rexfs.uniform(0,nfs)
rexrs = new Random()
rexrs.MCellRan4(highindex+9)
rexrs.uniform(0,nrs)
rob = new Random()
rob.MCellRan4(highindex+10)
rob.uniform(0, APIDENDMAX-1)
rtrp = new Random()
rtrp.MCellRan4(highindex+11)
rtrp.uniform(0, USER5MAX-1)
ror = new Random()
ror.MCellRan4(highindex+12)
ror.uniform(0, BASDENDMAX-1)
totSyn=28868+1379
access soma
soma distance()
proc advance() {
fadvance()
doNotify()
}
while(nsyn<650){
for r=0, sim{ // how many sims per syn #
fssin=int((27.771*log(nsyn) - 65.645)*nfs*0.01)
rssin=int((39.959*log(nsyn) - 160.57)*nrs*0.01)
if (fssin<=0){fssin=0}
if (fssin>=nfs){fssin=nfs}
if (rssin<=0){rssin=0}
if (rssin>=nrs){rssin=nrs}
for (j=0; j <= nsyn-1; j +=1) {
c=int(rex.repick())
loc=rd.repick()
if (c<14425){ //obliques exc
den=int(rob.repick())
apical_dendrite[den]{
Ens[j] = new NetStim(loc)
syn[j] = new Exp2Syn(loc)
nc[j] = new NetCon(Ens[j], syn[j],0,0,((A*distance(loc)^2)+B)*1.e-6)
}
}
if (c>14424 && c<14429){// trunk apical prox exc
den=int(rtrp.repick())
access user5[den]
if (distance(loc)<100){
user5[den]{
Ens[j] = new NetStim(loc)
syn[j] = new Exp2Syn(loc)
nc[j] = new NetCon(Ens[j], syn[j],0,0,((A*distance(loc)^2)+B)*1.e-6)
}}else{j=j-1}}
if (c>14428 && c<14706){ //trunk apical med exc
den=int(rtrp.repick())
access user5[den]
if (distance(loc)>100 && distance(loc)<350){
user5[den]{
Ens[j] = new NetStim(loc)
syn[j] = new Exp2Syn(loc)
nc[j] = new NetCon(Ens[j], syn[j],0,0,((A*distance(loc)^2)+B)*1.e-6)
}}else{j=j-1}
}
if (c>14705 && c<16877){ //trunk apical distal exc
den=int(rtrp.repick())
access user5[den]
if (distance(loc)>350 && distance(loc)<550){
user5[den]{
Ens[j] = new NetStim(loc)
syn[j] = new Exp2Syn(loc)
nc[j] = new NetCon(Ens[j], syn[j],0,0,((A*distance(loc)^2)+B)*1.e-6)
}}else{j=j-1}
}
if (c>16876 && c<17123){//basal prox exc
den=int(ror.repick())
access dendrite[den]
if (distance(loc)<50){
dendrite[den]{
Ens[j] = new NetStim(loc)
syn[j] = new Exp2Syn(loc)
nc[j] = new NetCon(Ens[j], syn[j],0,0,((A*distance(loc)^2)+B)*1.e-6)
}}else{j=j-1}
}
if (c>17122){ //basal distal exc
den=int(ror.repick())
access dendrite[den]
if (distance(loc)>50){
dendrite[den]{
Ens[j] = new NetStim(loc)
syn[j] = new Exp2Syn(loc)
nc[j] = new NetCon(Ens[j], syn[j],0,0,((A*distance(loc)^2)+B)*1.e-6)
}}else{j=j-1}
}
Ens[j].number = 1
Ens[j].start=pc.repick()
Ens[j].interval=0
Ens[j].noise=0
syn[j].e=0
syn[j].tau1 = TAU1e
syn[j].tau2 = TAU2e
}
for (y=0; y <= fssin-1; y +=1) {
loci=rd.repick()
d=int(rexfs.repick())
if (d<193){ // trunk apical prox inhi
den=int(rtrp.repick())
access user5[den]
if (distance(loci)<100){ //FS
user5[den]{
Ensi[y] = new NetStim(loci)
Ensi[y].number = 1
Ensi[y].interval = 0
Ensi[y].start=fs.repick()
Ensi[y].noise=0
syni[y] = new Exp2Syn(loci)
syni[y].e=-80
syni[y].tau1 = TAU1i
syni[y].tau2 = TAU2i
nci[y] = new NetCon(Ensi[y],syni[y],0,0,fs_sil)
}}else{y=y-1}}else{
den=int(ror.repick())//basal prox inhi
access dendrite[den]
if (distance(loci)<50){ //FS
dendrite[den]{
Ensi[y] = new NetStim(loci)
Ensi[y].number = 1
Ensi[y].interval = 0
Ensi[y].start=fs.repick()
Ensi[y].noise=0
syni[y] = new Exp2Syn(loci)
syni[y].e=-80
syni[y].tau1 = TAU1i
syni[y].tau2 = TAU2i
nci[y] = new NetCon(Ensi[y],syni[y],0,0,fs_sil)
}}else{y=y-1}}}
for (q=0; q <= rssin-1; q +=1) {
loci=rd.repick()
m=int(rexrs.repick())
if (m<438){
den=int(rob.repick()) //obliques inhi
apical_dendrite[den]{
Ensii[q] = new NetStim(loci)
Ensii[q].number = 1
Ensii[q].interval = 0
Ensii[q].noise=0
synii[q] = new Exp2Syn(loci)
synii[q].e=-80
synii[q].tau1 = TAU1i
synii[q].tau2 = TAU2i
if (distance(loci)>100){
Ensii[q].start=fs.repick()
ncii[q] = new NetCon(Ensii[q],synii[q],0,0,rs_sil)
}else{
Ensii[q].start=fs.repick()
ncii[q] = new NetCon(Ensii[q],synii[q],0,0,fs_sil)
}
}
}
if (m>437 && m<485){ //trunk dist inhi
den=int(rtrp.repick())
access user5[den]
if (distance(loci)>350 && distance(loci)<550){
user5[den]{
Ensii[q] = new NetStim(loci)
Ensii[q].number = 1
Ensii[q].interval = 0
Ensii[q].start=fs.repick()
Ensii[q].noise=0
synii[q] = new Exp2Syn(loci)
synii[q].e=-80
synii[q].tau1 = TAU1i
synii[q].tau2 = TAU2i
ncii[q] = new NetCon(Ensii[q],synii[q],0,0,rs_sil)
}}else{q=q-1}
}
if (m>484 && m<890){ // oriens dist inhi
den=int(ror.repick())
access dendrite[den]
if (distance(loci)>50){
dendrite[den]{
Ensii[q] = new NetStim(loci)
Ensii[q].number = 1
Ensii[q].interval = 0
Ensii[q].start=fs.repick()
Ensii[q].noise=0
synii[q] = new Exp2Syn(loci)
synii[q].e=-80
synii[q].tau1 = TAU1i
synii[q].tau2 = TAU2i
ncii[q] = new NetCon(Ensii[q],synii[q],0,0,rs_sil)
}}else{q=q-1}
}
if (m>889){ //trunk dist inhi
den=int(rtrp.repick())
access user5[den]
if (distance(loci)>100 && distance(loci)<350){
user5[den]{
Ensii[q] = new NetStim(loci)
Ensii[q].number = 1
Ensii[q].interval = 0
Ensii[q].start=fs.repick()
Ensii[q].noise=0
synii[q] = new Exp2Syn(loci)
synii[q].e=-80
synii[q].tau1 = TAU1i
synii[q].tau2 = TAU2i
ncii[q] = new NetCon(Ensii[q], synii[q],0,0,rs_sil)
}}else{q=q-1}
}}
for (q=0; q <= rssin-1; q +=1) {
loci=rd.repick()
m=int(rexrs.repick())
if (m<438){
den=int(rob.repick()) //obliques inhi
apical_dendrite[den]{
Ensii[q] = new NetStim(loci)
synii[q] = new Exp2Syn(loci)
if (distance(loci)>100){
Ensii[q].start=fs.repick()
ncii[q] = new NetCon(Ensii[q], synii[q],0,0,rs_sil)
}else{
Ensii[q].start=fs.repick()
ncii[q] = new NetCon(Ensii[q],synii[q],0,0,fs_sil)
}
}
}
if (m>437 && m<485){ //trunk dist inhi
den=int(rtrp.repick())
access user5[den]
if (distance(loci)>350 && distance(loci)<550){
user5[den]{
Ensii[q] = new NetStim(loci)
Ensii[q].start=fs.repick()
synii[q] = new Exp2Syn(loci)
ncii[q] = new NetCon(Ensii[q], synii[q],0,0,rs_sil)
}}else{q=q-1}
}
if (m>484 && m<890){ // oriens dist inhi
den=int(ror.repick())
access dendrite[den]
if (distance(loci)>50){
dendrite[den]{
Ensii[q] = new NetStim(loci)
Ensii[q].start=fs.repick()
synii[q] = new Exp2Syn(loci)
ncii[q] = new NetCon(Ensii[q], synii[q],0,0,rs_sil)
}}else{q=q-1}
}
if (m>889){ //trunk dist inhi
den=int(rtrp.repick())
access user5[den]
if (distance(loci)>100 && distance(loci)<350){
user5[den]{
Ensii[q] = new NetStim(loci)
Ensii[q].start=fs.repick()
synii[q] = new Exp2Syn(loci)
ncii[q] = new NetCon(Ensii[q], synii[q],0,0,rs_sil)
}}else{q=q-1}
}
Ensii[q].number = 1
Ensii[q].interval = 0
Ensii[q].noise=0
synii[q].e=-80
synii[q].tau1 = TAU1i
synii[q].tau2 = TAU2i
}
forsec "soma" {
apc = new APCount(.5)
apc.thresh=-20
}
run()
apcc=apcc+apc.n
print "sim# = ", r+1, "#syn = ", nsyn," Spike Prob. (%) = ",apcc/(r+1)
}
u.line(nsyn, apcc/(r+1))
u.flush()
nsyn=nsyn+80 // nsyn=nsyn+1 to replicate the paper, it was changed to speed up simulations
apcc=0
}
forall delete_section()
