load_file("nrngui.hoc")
use_mcell_ran4(1)
cvode_active(1)
numaxon=1
numsoma=1
numbasal=52
numapical=70
numtrunk=49
numuser5=numtrunk
numdendr=numbasal
numapdendr=numapical
low=50
high=400
high2=300
nsyn=50
tstop=300
Ih_rid=0
xopen("geo5038804.hoc")
xopen("fixnseg.hoc")
Rm = 28000
RmDend = Rm
RmSoma = Rm
RmAx = Rm
Cm = 1
CmSoma= Cm
CmAx = Cm
CmDend = Cm
RaAll= 150
RaSoma=150
RaAx = 50
Vrest = -65
dt = 0.1
gna_ax=.025
gna = .025
AXONM = 5
gkdr = 0.01
celsius = 35.0
KMULTPax = 0.03
ghd=0.00005
objref vec, diversi, apc, perc
objref ra, rb, rc, syn[nsyn], nc[nsyn], s[nsyn]
objref rd, syn2[nsyn],nc2[nsyn], s2[nsyn], weight_vec2, ritardo_vec, r
objref dann, weight_vec, riagg_vec
weight_vec=new Vector(11)
weight_vec.x[0]=0.875e-3
for i=0,9{
weight_vec.x[i+1]=weight_vec.x[i]+0.0625e-3}
weight_vec2=new Vector(11)
for j=0,10{
weight_vec2.x[j]=weight_vec.x[j]/3}
dann=new Vector()
dann.append(0,10,20,30,40,50,60,70,80,90,100,110,120,130,140,150)
riagg_vec=new Vector()
riagg_vec.append(10/10, 5/10, 6/10, 7/10)
ritardo_vec=new Vector()
ritardo_vec.append(5)
KA_rid_sper=60
kdr_rid_sper=40
Na_rid_sper=50
pes_rid_sper=50
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}
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}
soma{
apc=new APCount(.5)
apc.thresh=-10
geom_nseg()
tot=0
forall {tot=tot+nseg}
distance()
}
forsec "axon" {
insert nax gbar_nax=gna_ax * AXONM
insert kdr gkdrbar_kdr=gkdr
insert kap gkabar_kap = KMULTPax
}
forsec "soma" {
insert hd ghdbar_hd=ghd vhalfl_hd=-73
insert na3 gbar_na3=gna
insert kdr gkdrbar_kdr=gkdr
insert kap
}
for i=0, numbasal-1 dendrite[i] {
insert hd ghdbar_hd=ghd vhalfl_hd=-73
insert na3 gbar_na3=gna
insert kdr gkdrbar_kdr=gkdr
insert kap
insert kad
for (x) if (x>0 && x<1) { xdist = distance(x)
ghdbar_hd(x) = ghd*(1+3*xdist/100)
if (xdist > 100){
vhalfl_hd=-81
} else {
vhalfl_hd=-73
}
}
}
forsec "apical_dendrite" {
insert ds
insert hd ghdbar_hd=ghd
insert na3 gbar_na3=gna
insert kdr gkdrbar_kdr=gkdr
insert kap
insert kad
for (x) if (x>0 && x<1) { xdist = distance(x)
ghdbar_hd(x) = ghd*(1+3*xdist/100)
if (xdist > 100){
vhalfl_hd=-81
} else {
vhalfl_hd=-73
}
}
}
forsec "user5" {
insert ds
insert hd ghdbar_hd=ghd
insert na3 gbar_na3=gna
insert kdr gkdrbar_kdr=gkdr
insert kap
insert kad
for (x) if (x>0 && x<1) { xdist = distance(x)
ghdbar_hd(x) = ghd*(1+3*xdist/100)
if (xdist > 100){
vhalfl_hd=-81
} else {
vhalfl_hd=-73
}
}
}
proc membrane_area() {
vec = new Vector(172)
perc = new Vector()
{access soma[0]
tot=0
for(x,0) tot=tot+area(x)
vec.x[0]=tot
totsoma=tot}
totuser5=0
for i=0, numuser5-1 {access user5[i]
tot=0
for(x,0) tot=tot+area(x)
vec.x[i+numsoma]=tot
totuser5=totuser5+tot}
totdend=0
for i=0, numdendr-1 {access dendrite[i]
tot=0
for(x,0) tot=tot+area(x)
vec.x[i+numsoma+numuser5]=tot
totdend=totdend+tot}
tot_apdend=0
for i=0, numapdendr-1 {access apical_dendrite[i]
tot=0
for(x,0) tot=tot+area(x)
vec.x[i+numsoma+numuser5+numdendr]=tot
tot_apdend=tot_apdend+tot}
totarea=totsoma+totuser5+totdend+tot_apdend
zp=0
dp=totarea*10/100
vp=totarea*20/100
tp=totarea*30/100
qp=totarea*40/100
cp=totarea*50/100
sp=totarea*60/100
stp=totarea*70/100
op=totarea*80/100
np=totarea*90/100
cpc=55559.840
perc.append(zp, dp, vp, tp, qp, cp, sp, stp, op, np, cpc)
}
proc alzheimer(){
KMULT = 0.03
KMULTP = 0.03
KA_mir = riagg_vec.x[riagg]
forsec "soma" {
ghdbar_hd=ghd vhalfl_hd=-73
gbar_na3=gna
gkdrbar_kdr=gkdr
gkabar_kap = KMULTP
}
for i=0, numbasal-1 dendrite[i] {
ghdbar_hd=ghd vhalfl_hd=-73
gbar_na3=gna
gkdrbar_kdr=gkdr
gkabar_kap=0
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)
}
}
}
forsec "apical_dendrite" {
ghdbar_hd=ghd
gbar_na3=gna
gkdrbar_kdr=gkdr
gkabar_kap=0
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)
}
}
}
forsec "user5" {
ghdbar_hd=ghd
gbar_na3=gna
gkdrbar_kdr=gkdr
gkabar_kap=0
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)
}
}
}
diversi= new Vector()
areasottr=0
while (areasottr<percento) {
compsottrpr=int(r.repick())
if (diversi.contains(compsottrpr)==0){
compsottr=compsottrpr
diversi.append(compsottr)
Na_rid=Na_rid_sper*dann.x[rid]/100
kdr_rid=kdr_rid_sper*dann.x[rid]/100
KA_rid=KA_rid_sper*dann.x[rid]/100
if (compsottr<numsoma) {
soma[0] {
ghdbar_hd=ghd
gbar_na3=gna*(1-Na_rid/100)
gkdrbar_kdr=gkdr*(1-kdr_rid/100)
gkabar_kap = KMULTP*(1-KA_rid/100)*KA_mir
}
}
if (compsottr>=numsoma && compsottr<numsoma+numuser5){
user5[compsottr-numsoma] {
ghdbar_hd=ghd
gbar_na3=gna*(1-Na_rid/100)
gkdrbar_kdr=gkdr*(1-kdr_rid/100)
for (x) if (x>0 && x<1) { xdist = distance(x)
ghdbar_hd(x) = ghd*(1+3*xdist/100)
if (xdist > 100){
gkabar_kad(x) = KMULT*(1+xdist/100)*(1-KA_rid/100)*KA_mir
} else {
gkabar_kap(x) = KMULTP*(1+xdist/100)*(1-KA_rid/100)*KA_mir
}
}
}
}
if (compsottr>=numsoma+numuser5 && compsottr<numsoma+numuser5+numdendr){
dendrite[compsottr-numsoma-numuser5]{
ghdbar_hd=ghd
gbar_na3=gna*(1-Na_rid/100)
gkdrbar_kdr=gkdr*(1-kdr_rid/100)
for (x) if (x>0 && x<1) { xdist = distance(x)
ghdbar_hd(x) = ghd*(1+3*xdist/100)
if (xdist > 100){
gkabar_kad(x) = KMULT*(1+xdist/100)*(1-KA_rid/100)*KA_mir
} else {
gkabar_kap(x) = KMULTP*(1+xdist/100)*(1-KA_rid/100)*KA_mir
}
}
}
}
if (compsottr>=numsoma+numuser5+numdendr && compsottr<numsoma+numuser5+numdendr+numapdendr){
apical_dendrite[compsottr-numsoma-numuser5-numdendr]{
ghdbar_hd=ghd
gbar_na3=gna*(1-Na_rid/100)
gkdrbar_kdr=gkdr*(1-kdr_rid/100)
for (x) if (x>0 && x<1) { xdist = distance(x)
ghdbar_hd(x) = ghd*(1+3*xdist/100)
if (xdist > 100){
gkabar_kad(x) = KMULT*(1+xdist/100)*(1-KA_rid/100)*KA_mir
} else {
gkabar_kap(x) = KMULTP*(1+xdist/100)*(1-KA_rid/100)*KA_mir
}
}
}
}
areasottr=areasottr+vec.x[compsottr]
}
}
}
proc sinapsirandom(){
ritardo=ritardo_vec.x[rit]
rc.MCellRan4($1)
rc.normal(50, 5)
rd.MCellRan4($2)
rd.normal(50, 5)
objref nc[nsyn],nc2[nsyn]
objref s[nsyn], syn[nsyn] ,s2[nsyn], syn2[nsyn]
access soma
for i=0, nsyn-1{
s[i]=new NetStim(.5)
s[i].number=1
syn[i]=new Exp2Syn(.5)
syn[i].e=0
syn[i].tau1=.5
syn[i].tau2=3
s[i].start=rc.repick()+ritardo
nc[i]=new NetCon(s[i], syn[i], 0, 0, weight_vec.x[pes])
}
for i=0, nsyn-1{
s2[i]=new NetStim(.5)
s2[i].number=1
syn2[i]=new Exp2Syn(.5)
syn2[i].e=0
syn2[i].tau1=.5
syn2[i].tau2=10
s2[i].start=rd.repick()
nc2[i]=new NetCon(s2[i], syn2[i], 0, 0, weight_vec2.x[pes])
}
for i=0, nsyn-1{
j=0
while(j==0){
location=int(ra.repick())
tmp=rb.repick()
pes_rid=pes_rid_sper*dann.x[rid]/100
if(location>=numsoma && location<numsoma+numuser5){j=0}
if(location>=numsoma+numuser5 && location<numsoma+numuser5+numdendr){j=0}
if(location>=numsoma+numuser5+numdendr && location<numsoma+numuser5+numdendr+numapdendr){
apical_dendrite[location-numsoma-numuser5-numdendr]{
j=1
syn[i].loc(tmp)
if (diversi.contains(location)==1){nc[i].weight=weight_vec.x[pes]*(1-pes_rid/100)}
}
}
}
}
for i=0, nsyn-1{
j=0
while(j==0){
location=int(ra.repick())
tmp=rb.repick()
pes_rid=pes_rid_sper*dann.x[rid]/100
if(location>=numsoma && location<numsoma+numuser5){
user5[location-numsoma]{
if ( distance(tmp)<=high2) {j=0}else{
j=1
syn2[i].loc(tmp)
if (diversi.contains(location)==1){nc2[i].weight=weight_vec2.x[pes]*(1-pes_rid/100)
}
}
}
}
if(location>=numsoma+numuser5 && location<numsoma+numuser5+numdendr){j=0}
if(location>=numsoma+numuser5+numdendr && location<numsoma+numuser5+numdendr+numapdendr){j=0}
}
}
}
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
}
proc superrun() {
r= new Random()
r.uniform(0, 172)
ra=new Random()
ra.uniform(0,172)
rb=new Random()
rb.uniform(0,1)
rc=new Random()
rd=new Random()
r.MCellRan4(seed)
ra.MCellRan4(seeda)
rb.MCellRan4(seedb)
membrane_area()
percento=perc.x[amp]
alzheimer()
sinapsirandom(seedc,seedd)
run()
}
load_file("10sim.ses")
PlotShape[0].exec_menu("Shape Plot")
PlotShape[0].exec_menu("Show Diam")
rit=0
rid=10
pes=5
proc control() {
Graph[0].erase()
loop=0
nspike=0
seeda=70
seedb=70+5
seedc=70+10
seedd=90
amp=0
riagg=0
print "CONTROL"
for(loop==0; loop<=9; loop=loop+1) {
seed=seed+100
seeda=seeda+100
seedb=seedb+100
seedc=seedc+100
seedd=seedd+100
superrun()
if (apc.n==0) {print "sim ", loop+1, ": no spike"} else {print "sim ", loop+1, ": spike"}
nspike=nspike+apc.n}
print " number of spikes = ", nspike
}
proc AD(){
Graph[0].erase()
loop=0
nspike=0
seeda=70
seedb=70+5
seedc=70+10
seedd=90
amp=9
riagg=0
print "AD"
for(loop==0; loop<=9; loop=loop+1) {
seed=seed+100
seeda=seeda+100
seedb=seedb+100
seedc=seedc+100
seedd=seedd+100
superrun()
if (apc.n==0) {print "sim ", loop+1, ": no spike"} else {print "sim ", loop+1, ": spike"}
nspike=nspike+apc.n}
print " number of spikes = ", nspike
}
proc AD_KA(){
Graph[0].erase()
loop=0
nspike=0
seeda=70
seedb=70+5
seedc=70+10
seedd=90
amp=9
riagg=2
print "KA-TREATMENT"
for(loop==0; loop<=9; loop=loop+1) {
seed=seed+100
seeda=seeda+100
seedb=seedb+100
seedc=seedc+100
seedd=seedd+100
superrun()
if (apc.n==0) {print "sim ", loop+1, ": no spike"} else {print "sim ", loop+1, ": spike"}
nspike=nspike+apc.n}
print " number of spikes = ", nspike
}
