#hoc-code based on implementation https://senselab.med.yale.edu/modeldb/showModel.cshtml?model=151825
#(CC BY 3.0) Tuomo Maki-Marttunen
from neuron import h
import matplotlib
matplotlib.use('Agg')
import numpy
from pylab import *
import mytools
import pickle
import time
import sys
v0 = -62
ca0 = 0.0001
proximalpoint = 400
distalpoint = 620
#distalpoint = 960
BACdt = 5.0
fs = 8
coeffCoeffs = [[0.25,0],[0.125,0],[0.5,0],[0.5,1.0/3],[0.5,2.0/3],[0.5,1.0],[-0.25,0],[-0.125,0],[-0.5,0]]
import mutation_stuff
MT = mutation_stuff.getMT()
defVals = mutation_stuff.getdefvals()
keyList = defVals.keys()
mySuffixes = mutation_stuff.getsuffixes()
mySuffixExceptions = mutation_stuff.getsuffixexceptions()
unpicklefile = open('scalings.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
theseCoeffsAll = unpickledlist[0]
theseMutValsAll = unpickledlist[2]
spTimesAll = []
timesAll = []
VsomasAll = []
CasomasAll = []
VdendsAll = []
CadendsAll = []
ISIs_all = []
InasomasAll = []
IcahvasomasAll = []
IcalvasomasAll = []
IhsomasAll = []
IsksomasAll = []
IbksomasAll = []
InadendsAll = []
IcahvadendsAll = []
IcalvadendsAll = []
IhdendsAll = []
IskdendsAll = []
IbkdendsAll = []
h("""
load_file("myrun.hoc")
objref cvode
cvode = new CVode()
cvode.active(1)
cvode.atol(0.001)
access a_soma
objref st1,syn1, sl
a_soma st1 = new IClamp(0.5)
double siteVec[2]
sl = new List()
sl=locateSites("apic",620)
maxdiam = 0
for(i=0;i<sl.count();i+=1){
dd1 = sl.o[i].x[1]
dd = apic[sl.o[i].x[0]].diam(dd1)
if (dd > maxdiam) {
j = i
maxdiam = dd
}
}
siteVec[0] = sl.o[j].x[0]
siteVec[1] = sl.o[j].x[1]
apic[siteVec[0]] syn1 = new AlphaSynapse(siteVec[1])
//apic[41] syn1 = new AlphaSynapse(0.5)
syn1.onset = 3400
syn1.tau = 3
syn1.gmax = 0.0
syn1.e = 50
objref vsoma, vdend, casoma, cadend, tvec, inasoma, icahvasoma, icalvasoma, ihsoma, isksoma, ibksoma, inadend, icahvadend, icalvadend, ihdend, iskdend, ibkdend, iktsoma, ikpsoma, iktdend, ikpdend
vsoma = new Vector()
vdend = new Vector()
casoma = new Vector()
cadend = new Vector()
inasoma = new Vector()
icahvasoma = new Vector()
icalvasoma = new Vector()
ihsoma = new Vector()
isksoma = new Vector()
ibksoma = new Vector()
inadend = new Vector()
icahvadend = new Vector()
icalvadend = new Vector()
ihdend = new Vector()
iskdend = new Vector()
ibkdend = new Vector()
iktsoma = new Vector()
ikpsoma = new Vector()
iktdend = new Vector()
ikpdend = new Vector()
tvec = new Vector()
a_soma cvode.record(&v(0.5),vsoma,tvec)
a_soma cvode.record(&cai(0.5),casoma,tvec)
a_soma cvode.record(&ina_na(0.5),inasoma,tvec)
a_soma cvode.record(&ica_cah(0.5),icahvasoma,tvec)
a_soma cvode.record(&ica_car(0.5),icalvasoma,tvec)
a_soma cvode.record(&ih_iH(0.5),ihsoma,tvec)
a_soma cvode.record(&ik_sk(0.5),isksoma,tvec)
a_soma cvode.record(&ik_bk(0.5),ibksoma,tvec)
a_soma cvode.record(&ik_iA(0.5),iktsoma,tvec)
a_soma cvode.record(&ik_kslow(0.5),ikpsoma,tvec)
apic[siteVec[0]] cvode.record(&v(siteVec[1]),vdend,tvec)
apic[siteVec[0]] cvode.record(&cai(siteVec[1]),cadend,tvec)
apic[siteVec[0]] cvode.record(&ina_na(siteVec[1]),inadend,tvec)
apic[siteVec[0]] cvode.record(&ica_cah(siteVec[1]),icahvadend,tvec)
apic[siteVec[0]] cvode.record(&ica_car(siteVec[1]),icalvadend,tvec)
apic[siteVec[0]] cvode.record(&ih_iH(siteVec[1]),ihdend,tvec)
apic[siteVec[0]] cvode.record(&ik_sk(siteVec[1]),iskdend,tvec)
apic[siteVec[0]] cvode.record(&ik_bk(siteVec[1]),ibkdend,tvec)
apic[siteVec[0]] cvode.record(&ik_iA(0.5),iktdend,tvec)
apic[siteVec[0]] cvode.record(&ik_kslow(0.5),ikpdend,tvec)
v_init = -62
dt = 0.025
tstop = 1000
""")
counter = -1
for igene in range(0,len(MT)):
spTimesThisGene = []
timesThisGene = []
VsomasThisGene = []
CasomasThisGene = []
VdendsThisGene = []
CadendsThisGene = []
InasomasThisGene = []
IcahvasomasThisGene = []
IcalvasomasThisGene = []
IhsomasThisGene = []
IsksomasThisGene = []
IbksomasThisGene = []
InadendsThisGene = []
IcahvadendsThisGene = []
IcalvadendsThisGene = []
IhdendsThisGene = []
IskdendsThisGene = []
IbkdendsThisGene = []
for imut in range(0,len(MT[igene])):
spTimesThisMut = []
timesThisMut = []
VsomasThisMut = []
CasomasThisMut = []
VdendsThisMut = []
CadendsThisMut = []
InasomasThisMut = []
IcahvasomasThisMut = []
IcalvasomasThisMut = []
IhsomasThisMut = []
IsksomasThisMut = []
IbksomasThisMut = []
InadendsThisMut = []
IcahvadendsThisMut = []
IcalvadendsThisMut = []
IhdendsThisMut = []
IskdendsThisMut = []
IbkdendsThisMut = []
IktsomasThisMut = []
IkpsomasThisMut = []
IktdendsThisMut = []
IkpdendsThisMut = []
nVals = len(MT[igene][imut])*[0]
thesemutvars = []
theseCoeffs = theseCoeffsAll[igene][imut]
for imutvar in range(0,len(MT[igene][imut])):
thesemutvars.append(MT[igene][imut][imutvar][0])
if type(MT[igene][imut][imutvar][1]) is int or type(MT[igene][imut][imutvar][1]) is float:
MT[igene][imut][imutvar][1] = [MT[igene][imut][imutvar][1]]
nVals[imutvar] = len(MT[igene][imut][imutvar][1])
cumprodnVals = cumprod(nVals)
allmutvars = cumprodnVals[len(MT[igene][imut])-1]*[thesemutvars]
allmutvals = []
for iallmutval in range(0,cumprodnVals[len(MT[igene][imut])-1]):
allmutvals.append([0]*len(thesemutvars))
for iallmutval in range(0,cumprodnVals[len(MT[igene][imut])-1]):
for imutvar in range(0,len(MT[igene][imut])):
if imutvar==0:
allmutvals[iallmutval][imutvar] = MT[igene][imut][imutvar][1][iallmutval%nVals[imutvar]]
else:
allmutvals[iallmutval][imutvar] = MT[igene][imut][imutvar][1][(iallmutval/cumprodnVals[imutvar-1])%nVals[imutvar]]
for iallmutval in range(0,cumprodnVals[len(MT[igene][imut])-1]):
counter = counter + 1
if len(sys.argv) > 1 and int(float(sys.argv[1])) != counter:
continue
spTimesThisMutVal = []
timesThisMutVal = []
VsomasThisMutVal = []
CasomasThisMutVal = []
VdendsThisMutVal = []
CadendsThisMutVal = []
InasomasThisMutVal = []
IcahvasomasThisMutVal = []
IcalvasomasThisMutVal = []
IhsomasThisMutVal = []
IsksomasThisMutVal = []
IbksomasThisMutVal = []
InadendsThisMutVal = []
IcahvadendsThisMutVal = []
IcalvadendsThisMutVal = []
IhdendsThisMutVal = []
IskdendsThisMutVal = []
IbkdendsThisMutVal = []
IktsomasThisMutVal = []
IkpsomasThisMutVal = []
IktdendsThisMutVal = []
IkpdendsThisMutVal = []
for iter in [0, 2, 5, 6, 8, -1]:
if iter >= 0:
thisCoeff = coeffCoeffs[iter][0]*theseCoeffs[iallmutval] + coeffCoeffs[iter][1]*(1.0 - 0.5*theseCoeffs[iallmutval])
else:
thisCoeff = 0
if iter == -1 and (igene > 0 or imut > 0 or iallmutval > 0):
continue # do the control only once!
mutText = ""
for imutvar in range(0,len(MT[igene][imut])):
if imutvar > 0 and imutvar%2==0:
mutText = mutText+"\n"
mutvars = allmutvars[iallmutval][imutvar]
mutvals = allmutvals[iallmutval][imutvar]
if type(mutvars) is str:
mutvars = [mutvars]
mutText = mutText + str(mutvars) + ": "
for kmutvar in range(0,len(mutvars)):
mutvar = mutvars[kmutvar]
if (mutvars[kmutvar].find('off') > -1 and mutvars[kmutvar].find('offc') < 0) or mutvars[kmutvar].find('eh') > -1:
newVal = defVals[mutvar]+mutvals*thisCoeff
if mutvals >= 0 and kmutvar==0:
mutText = mutText + "+" + str(mutvals) +" mV"
elif kmutvar==0:
mutText = mutText + str(mutvals) +" mV"
else:
newVal = defVals[mutvar]*(mutvals**thisCoeff)
if kmutvar==0:
mutText = mutText + "*" + str(mutvals)
if kmutvar < len(mutvars)-1:
mutText = mutText + ", "
mySuffix = mutvars[kmutvar][mutvars[kmutvar].find('_')+1:len(mutvars[kmutvar])]
mySuffixInd = next((i for i,x in enumerate(mySuffixes) if x.find(mySuffix) > -1))
isException = 0
for jsuffe in range(0,len(mySuffixExceptions[mySuffixInd])):
if mySuffixExceptions[mySuffixInd][jsuffe][0].find(mutvars[kmutvar]) > -1:
isException = 1
exceptionInd = jsuffe
if not isException:
print ("""forall if(ismembrane(\""""+mySuffix+"""\")) """+mutvars[kmutvar]+""" = """+str(newVal))
h("""forall if(ismembrane(\""""+mySuffix+"""\")) """+mutvars[kmutvar]+""" = """+str(newVal))
else:
print ("""forall if(ismembrane(\""""+mySuffix+"""\")) """+mySuffixExceptions[isuffix][j][1]+""" = """+str(newVal))
h("""forall if(ismembrane(\""""+mySuffix+"""\")) """+mySuffixExceptions[isuffix][j][1]+""" = """+str(newVal))
print mutText
tstop = 4000.0
squareAmp = 0.8
squareDur = 3800.0
h("""
tstop = """+str(tstop)+"""
v_init = """+str(v0)+"""
cai0_ca_ion = """+str(ca0)+"""
st1.amp = """+str(squareAmp)+"""
st1.del = 200
st1.dur = """+str(squareDur)+"""
syn1.gmax = 0
""")
h.init()
h.run()
times=np.array(h.tvec)
Vsoma=np.array(h.vsoma)
Vdend=np.array(h.vdend)
Casoma=np.array(h.casoma)
Cadend=np.array(h.cadend)
Inasoma=np.array(h.inasoma)
Icahvasoma=np.array(h.icahvasoma)
Icalvasoma=np.array(h.icalvasoma)
Ihsoma=np.array(h.ihsoma)
Isksoma=np.array(h.isksoma)
Ibksoma=np.array(h.ibksoma)
Inadend=np.array(h.inadend)
Icahvadend=np.array(h.icahvadend)
Icalvadend=np.array(h.icalvadend)
Ihdend=np.array(h.ihdend)
Iskdend=np.array(h.iskdend)
Ibkdend=np.array(h.ibkdend)
Iktsoma=np.array(h.iktsoma)
Ikpsoma=np.array(h.ikpsoma)
Iktdend=np.array(h.iktdend)
Ikpdend=np.array(h.ikpdend)
spikes = mytools.spike_times(times,Vsoma,-50,-50)
spTimesThisCoeff = spikes[:]
nSpikes1 = len(spikes)
if nSpikes1 > 7:
spts = spikes[len(spikes)-6:len(spikes)]
istart = next((i for i,x in enumerate(times) if x > spts[0]))
iend = next((i for i,x in enumerate(times) if x > spts[4]))+7
nsteps = iend-istart-1
tdiff = [y-x for x,y in zip(times[istart:iend-1],times[istart+1:iend])]
cadiff = [y-x for x,y in zip(Casoma[istart:iend-1],Casoma[istart+1:iend])]
caddiff = [y-x for x,y in zip(Cadend[istart:iend-1],Cadend[istart+1:iend])]
caderiv1 = [y/x for x,y in zip(tdiff[0:nsteps-1],cadiff[0:nsteps-1])]
caderiv2 = [y/x for x,y in zip(tdiff[1:nsteps],cadiff[1:nsteps])]
caderiv = [(x+y)/2.0 for x,y in zip(caderiv1,caderiv2)]
cadderiv = [y/x for x,y in zip(tdiff,caddiff)]
#Restore default values:
for imutvar in range(0,len(MT[igene][imut])):
mutvars = allmutvars[iallmutval][imutvar]
mutvals = allmutvals[iallmutval][imutvar]
if type(mutvars) is str:
mutvars = [mutvars]
for kmutvar in range(0,len(mutvars)):
newVal = defVals[mutvars[kmutvar]]
mySuffix = mutvars[kmutvar][mutvars[kmutvar].find('_')+1:len(mutvars[kmutvar])]
mySuffixInd = next((i for i,x in enumerate(mySuffixes) if x.find(mySuffix) > -1))
isException = 0
for jsuffe in range(0,len(mySuffixExceptions[mySuffixInd])):
if mySuffixExceptions[mySuffixInd][jsuffe][0].find(mutvars[kmutvar]) > -1:
isException = 1
exceptionInd = jsuffe
if not isException:
h("""forall if(ismembrane(\""""+mySuffix+"""\")) """+mutvars[kmutvar]+""" = """+str(defVals[mutvars[kmutvar]]))
else:
h("""forall if(ismembrane(\""""+mySuffix+"""\")) """+mySuffixExceptions[isuffix][j][1]+""" = """+str(defVals[mutvars[kmutvar]]))
spTimesThisMutVal.append(spTimesThisCoeff[:])
timesThisMutVal.append(times[:])
VsomasThisMutVal.append(Vsoma[:])
CasomasThisMutVal.append(Casoma[:])
VdendsThisMutVal.append(Vdend[:])
CadendsThisMutVal.append(Cadend[:])
InasomasThisMutVal.append(Inasoma[:])
IcahvasomasThisMutVal.append(Icahvasoma[:])
IcalvasomasThisMutVal.append(Icalvasoma[:])
IhsomasThisMutVal.append(Ihsoma[:])
IsksomasThisMutVal.append(Isksoma[:])
IbksomasThisMutVal.append(Ibksoma[:])
InadendsThisMutVal.append(Inadend[:])
IcahvadendsThisMutVal.append(Icahvadend[:])
IcalvadendsThisMutVal.append(Icalvadend[:])
IhdendsThisMutVal.append(Ihdend[:])
IskdendsThisMutVal.append(Iskdend[:])
IbkdendsThisMutVal.append(Ibkdend[:])
IktsomasThisMutVal.append(Iktsoma[:])
IkpsomasThisMutVal.append(Ikpsoma[:])
IktdendsThisMutVal.append(Iktdend[:])
IkpdendsThisMutVal.append(Ikpdend[:])
if iter==-1:
picklelist = [theseCoeffsAll,times,Vsoma,Casoma,Vdend,Cadend,Inasoma, Icahvasoma, Icalvasoma, Ihsoma, Isksoma, Ibksoma,Inadend, Icahvadend, Icalvadend, Ihdend, Iskdend, Ibkdend, Iktsoma, Ikpsoma, Iktdend, Ikpdend, MT]
file = open('steadystate_control.sav', 'w')
pickle.dump(picklelist,file)
file.close()
spTimesThisMut.append(spTimesThisMutVal[:])
timesThisMut.append(timesThisMutVal[:])
VsomasThisMut.append(VsomasThisMutVal[:])
CasomasThisMut.append(CasomasThisMutVal[:])
VdendsThisMut.append(VdendsThisMutVal[:])
CadendsThisMut.append(CadendsThisMutVal[:])
InasomasThisMut.append(InasomasThisMutVal[:])
IcahvasomasThisMut.append(IcahvasomasThisMutVal[:])
IcalvasomasThisMut.append(IcalvasomasThisMutVal[:])
IhsomasThisMut.append(IhsomasThisMutVal[:])
IsksomasThisMut.append(IsksomasThisMutVal[:])
IbksomasThisMut.append(IbksomasThisMutVal[:])
InadendsThisMut.append(InadendsThisMutVal[:])
IcahvadendsThisMut.append(IcahvadendsThisMutVal[:])
IcalvadendsThisMut.append(IcalvadendsThisMutVal[:])
IhdendsThisMut.append(IhdendsThisMutVal[:])
IskdendsThisMut.append(IskdendsThisMutVal[:])
IbkdendsThisMut.append(IbkdendsThisMutVal[:])
IktsomasThisMut.append(IktsomasThisMutVal[:])
IkpsomasThisMut.append(IkpsomasThisMutVal[:])
IktdendsThisMut.append(IktdendsThisMutVal[:])
IkpdendsThisMut.append(IkpdendsThisMutVal[:])
picklelist = [theseCoeffsAll,timesThisMutVal,VsomasThisMutVal,CasomasThisMutVal,VdendsThisMutVal,CadendsThisMutVal,
InasomasThisMutVal, IcahvasomasThisMutVal, IcalvasomasThisMutVal, IhsomasThisMutVal, IsksomasThisMutVal, IbksomasThisMutVal,
InadendsThisMutVal, IcahvadendsThisMutVal, IcalvadendsThisMutVal, IhdendsThisMutVal, IskdendsThisMutVal, IbkdendsThisMutVal, IktsomasThisMutVal, IkpsomasThisMutVal, IktdendsThisMutVal, IkpdendsThisMutVal,MT]
file = open('steadystate_'+str(igene)+'_'+str(imut)+'_'+str(iallmutval)+'.sav', 'w')
pickle.dump(picklelist,file)
file.close()
spTimesThisGene.append(spTimesThisMut[:])
timesThisGene.append(timesThisMut[:])
VsomasThisGene.append(VsomasThisMut[:])
CasomasThisGene.append(CasomasThisMut[:])
VdendsThisGene.append(VdendsThisMut[:])
CadendsThisGene.append(CadendsThisMut[:])
spTimesAll.append(spTimesThisGene[:])
timesAll.append(timesThisGene[:])
VsomasAll.append(VsomasThisGene[:])
CasomasAll.append(CasomasThisGene[:])
VdendsAll.append(VdendsThisGene[:])
CadendsAll.append(CadendsThisGene[:])
#picklelist = [theseCoeffsAll,VsomasAll,CasomasAll,VdendsAll,CadendsAll,MT]
#file = open('steadystate.sav', 'w')
#pickle.dump(picklelist,file)
#file.close()