from neuron import h
import matplotlib
matplotlib.use('Agg')
import numpy
from pylab import *
import mytools
import pickle
import time
import sys
from setparams import *
morphology_file = "morphologies/cell1.asc"
biophys_file = "models/L5PCbiophys3.hoc"
template_file = "models/L5PCtemplate.hoc"
v0 = -80
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()
for idefval in range(0,len(keyList)):
if type(defVals[keyList[idefval]]) is not list:
defVals[keyList[idefval]] = [defVals[keyList[idefval]], defVals[keyList[idefval]]] #make the dictionary values [somatic, apical]
updatedVars = ['somatic','apical','basal'] # the possible classes of segments that defVals may apply to
whichDefVal = [0,1,0] # use the defVal[0] for somatic and basal segments and defVal[1] for apical segments
unpicklefile = open('scalings_cs.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
theseCoeffsAllAll = unpickledlist[0]
theseMutValsAll = unpickledlist[2]
paramdicts = []
paramdicts.append({}) # 1 spike per burst, control
paramdicts.append({'A_gNaTa_tbar_NaTa_t': 1.6}) # 1-2 spikes per burst
paramdicts.append({'A_gNaTa_tbar_NaTa_t': 2.2}) # 2-3 spikes per burst
paramdicts.append({'A_gNaTa_tbar_NaTa_t': 2.2, 'S_gCa_HVAbar_Ca_HVA': 0.9}) # 3-4 spikes per burst
paramdicts.append({'A_gNaTa_tbar_NaTa_t': 2.2, 'S_gCa_HVAbar_Ca_HVA': 0.625}) # 3-5 spikes per burst
paramdicts.append({'A_gNaTa_tbar_NaTa_t': 2.2, 'S_gCa_HVAbar_Ca_HVA': 0.5}) # 4-6 spikes per burst
paramdicts.append({'A_gNaTa_tbar_NaTa_t': 2.2, 'S_gCa_HVAbar_Ca_HVA': 0.3}) # 5-9 spikes per burst
spTimesAllAll = []
timesAllAll = []
VsomasAllAll = []
CasomasAllAll = []
VdendsAllAll = []
CadendsAllAll = []
for icell in range(0,7):
theseCoeffsAll = theseCoeffsAllAll[icell]
spTimesAll = []
spTimesAll2 = []
ISIs_all = []
morphology_file = "morphologies/cell1.asc"
biophys_file = "models/L5PCbiophys3.hoc"
template_file = "models/L5PCtemplate.hoc"
h("""
load_file("stdlib.hoc")
load_file("stdrun.hoc")
objref cvode
cvode = new CVode()
cvode.active(1)
load_file("import3d.hoc")
objref L5PC
load_file(\""""+biophys_file+"""\")
load_file(\""""+template_file+"""\")
L5PC = new L5PCtemplate(\""""+morphology_file+"""\")
objref st1
st1 = new IClamp(0.5)
L5PC.soma st1
forsec L5PC.somatic {
}
forsec L5PC.apical {
}
L5PC.distribute_channels("apic","gIhbar_Ih",2,-0.8696,3.6161,0.0,1.0*2.0870,0.0002)
L5PC.distribute_channels("apic","gCa_HVAbar_Ca_HVA",3,1.0,0.1,685.0,885.0,1.0*0.000555)
L5PC.distribute_channels("apic","gCa_LVAstbar_Ca_LVAst",3,1.0,0.01,685.0,885.0,1.0*0.0187)
objref sl,st2,ns,syn1,con1,isyn, tvec
isyn = new Vector()
tvec = new Vector()
sl = new List()
double siteVec[2]
sl = L5PC.locateSites("apic","""+str(distalpoint)+""")
maxdiam = 0
for(i=0;i<sl.count();i+=1){
dd1 = sl.o[i].x[1]
dd = L5PC.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]
print "distalpoint gCa_HVA: ", L5PC.apic[siteVec[0]].gCa_HVAbar_Ca_HVA
print "distalpoint gCa_LVA: ", L5PC.apic[siteVec[0]].gCa_LVAstbar_Ca_LVAst
access L5PC.apic[siteVec[0]]
st2 = new IClamp(siteVec[1])
st2.amp = 0
L5PC.apic[siteVec[0]] {
st2
syn1 = new epsp(siteVec[1])
syn1.tau0 = 0.5
syn1.tau1 = 5
syn1.onset = 145 + """+str(BACdt)+"""
cvode.record(&syn1.i,isyn,tvec)
}
objref vsoma, vdend, recSite, vdend2, isoma, cadend, cadend2, casoma
vsoma = new Vector()
casoma = new Vector()
vdend = new Vector()
cadend = new Vector()
vdend2 = new Vector()
cadend2 = new Vector()
access L5PC.soma
cvode.record(&v(0.5),vsoma,tvec)
cvode.record(&cai(0.5),casoma,tvec)
access L5PC.apic[siteVec[0]]
cvode.record(&v(siteVec[1]),vdend,tvec)
cvode.record(&cai(siteVec[1]),cadend,tvec)
sl = new List()
sl = L5PC.locateSites("apic","""+str(proximalpoint)+""")
maxdiam = 0
for(i=0;i<sl.count();i+=1){
dd1 = sl.o[i].x[1]
dd = L5PC.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]
print "proximalpoint gCa_HVA: ", L5PC.apic[siteVec[0]].gCa_HVAbar_Ca_HVA
print "proximalpoint gCa_LVA: ", L5PC.apic[siteVec[0]].gCa_LVAstbar_Ca_LVAst
access L5PC.apic[siteVec[0]]
recSite = new IClamp(siteVec[1])
recSite.amp = 0
L5PC.apic[siteVec[0]] {
recSite
}
access L5PC.apic[siteVec[0]]
cvode.record(&v(siteVec[1]),vdend2,tvec)
cvode.record(&cai(siteVec[1]),cadend2,tvec)
access L5PC.soma
isoma = new Vector()
cvode.record(&st1.i,isoma,tvec)
""")
paramdict = paramdicts[icell]
setparams(paramdict)
spTimesAll = []
timesAll = []
VsomasAll = []
CasomasAll = []
VdendsAll = []
CadendsAll = []
counter = -1
for igene in range(0,len(MT)):
spTimesThisGene = []
timesThisGene = []
VsomasThisGene = []
CasomasThisGene = []
VdendsThisGene = []
CadendsThisGene = []
for imut in range(0,len(MT[igene])):
spTimesThisMut = []
timesThisMut = []
VsomasThisMut = []
CasomasThisMut = []
VdendsThisMut = []
CadendsThisMut = []
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 = []
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 mutvar.find('offm') > -1 or mutvar.find('offh') > -1 or mutvar.find('ehcn') > -1:
newVal = [x+mutvals*thisCoeff for x in defVals[mutvar]]
if mutvals >= 0 and kmutvar==0:
mutText = mutText + "+" + str(mutvals) +" mV"
elif kmutvar==0:
mutText = mutText + str(mutvals) +" mV"
else:
newVal = [x*(mutvals**thisCoeff) for x in defVals[mutvar]]
if kmutvar==0:
mutText = mutText + "*" + str(mutvals)
if kmutvar < len(mutvars)-1:
mutText = mutText + ", "
if mutvar.find('_Ih') > -1:
updateThese = [1,1,1]
elif mutvar.find('_Ca_HVA') > -1 or mutvar.find('_Ca_LVAst') > -1 or mutvar.find('_SKv3.1') > -1 or mutvar.find('_Ca_HVA') > -1 or mutvar.find('_SK_E2') > -1 or mutvar.find('_NaTa_t') > -1 or mutvar.find('_CaDynamics_E2') > -1:
updateThese = [1,1,0]
elif mutvar.find('_K_Pst') > -1 or mutvar.find('_K_Tst') > -1 or mutvar.find('_Nap_Et2') > -1:
updateThese = [1,0,0]
elif mutvar.find('_Im') > -1:
updateThese = [0,1,0]
else:
print "Error: str=" + str(mutvar)
updatedThese = [0,0,0]
for iupdated in range(0,3):
if updateThese[iupdated]:
print """forsec L5PC."""+str(updatedVars[iupdated])+""" {
"""+mutvar+""" = """+str(newVal[whichDefVal[iupdated]])+"""
}"""
h("""forsec L5PC."""+str(updatedVars[iupdated])+""" {
"""+mutvar+""" = """+str(newVal[whichDefVal[iupdated]])+"""
}""")
print mutText
tstop = 4000.0
squareAmp = 1.2
squareDur = 3800.0
epsp_Imax = 0.0
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.imax = """+str(epsp_Imax)+"""
""")
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)
spikes = mytools.spike_times(times,Vsoma,-20,-45)
spTimesThisCoeff = spikes[:]
nSpikes1 = len(spikes)
if nSpikes1 > 5:
spts = spikes[len(spikes)-3: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[1]))+4
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)]
#Print the parameters and their default values:
for idefval in range(0,len(defVals.keys())):
thisdefval = defVals.keys()[idefval]
if thisdefval.find('_Im') > -1:
h('print "L5PC.apic[0].'+thisdefval+' = ", L5PC.apic[0].'+thisdefval+', "Default = ", '+str(defVals[thisdefval][1]))
#) #+" (def="+str(defVals[thisdefval])+")"
else:
h('print "L5PC.soma[0].'+thisdefval+' = ", L5PC.soma[0].'+thisdefval+', "Default = ", '+str(defVals[thisdefval][0]))
#h('print L5PC.soma[0]."+thisdefval) #+" (def="+str(defVals[thisdefval])+")"
#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)):
mutvar = mutvars[kmutvar]
newVal = defVals[mutvar]
if mutvar.find('_Ih') > -1:
updateThese = [1,1,1]
elif mutvar.find('_Ca_HVA') > -1 or mutvar.find('_Ca_LVAst') > -1 or mutvar.find('_SKv3.1') > -1 or mutvar.find('_Ca_HVA') > -1 or mutvar.find('_SK_E2') > -1 or mutvar.find('_NaTa_t') > -1 or mutvar.find('_CaDynamics_E2') > -1:
updateThese = [1,1,0]
elif mutvar.find('_K_Pst') > -1 or mutvar.find('_K_Tst') > -1 or mutvar.find('_Nap_Et2') > -1:
updateThese = [1,0,0]
elif mutvar.find('_Im') > -1:
updateThese = [0,1,0]
else:
print "Error: str=" + str(mutvar)
updatedThese = [0,0,0]
for iupdated in range(0,3):
if updateThese[iupdated]:
print """forsec L5PC."""+str(updatedVars[iupdated])+""" {
"""+mutvar+""" = """+str(newVal[whichDefVal[iupdated]])+"""
}"""
h("""forsec L5PC."""+str(updatedVars[iupdated])+""" {
"""+mutvar+""" = """+str(newVal[whichDefVal[iupdated]])+"""
}""")
spTimesThisMutVal.append(spTimesThisCoeff[:])
timesThisMutVal.append(times[:])
VsomasThisMutVal.append(Vsoma[:])
CasomasThisMutVal.append(Casoma[:])
VdendsThisMutVal.append(Vdend[:])
CadendsThisMutVal.append(Cadend[:])
if iter==-1:
picklelist = [theseCoeffsAllAll,times,Vsoma,Casoma,Vdend,Cadend,MT]
file = open('steadystate_cs'+str(icell)+'_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[:])
picklelist = [theseCoeffsAllAll,timesThisMutVal,VsomasThisMutVal,CasomasThisMutVal,VdendsThisMutVal,CadendsThisMutVal,MT]
file = open('steadystate_cs'+str(icell)+'_'+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[:])
spTimesAllAll.append(spTimesAll[:])
timesAllAll.append(timesAll[:])
VsomasAllAll.append(VsomasAll[:])
CasomasAllAll.append(CasomasAll[:])
VdendsAllAll.append(VdendsAll[:])
CadendsAllAll.append(CadendsAll[:])
#picklelist = [theseCoeffsAllAll,VsomasAllAll,CasomasAllAll,VdendsAllAll,CadendsAllAll,MT]
#file = open('steadystate.sav', 'w')
#pickle.dump(picklelist,file)
#file.close()