from neuron import h
import matplotlib
matplotlib.use('Agg')
import numpy
from pylab import *
import mytools
import pickle
import sys
from setparams import *
from os.path import exists
v0 = -80
ca0 = 0.0001
proximalpoint = 400
distalpoint = 620
#distalpoint = 960
BACdt = 5.0
Is = [0.35+0.05*x for x in range(0,22)]
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]
spTimesAllAll = []
spTimesAllAll2 = []
ISIs_allAll = []
spTimesAllAll = []
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
cellcounter = -1
for icell in range(0,len(paramdicts)):
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)
cvode.atol(0.001)
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
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 = 200 + """+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]
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)
styles = ['g-','g-','g-','g-','g-','g-','g-','g-','g-']
#cols = ['#00aaaa','#11cc44','#55ee00','#bbaa00','#ee6600','#ff0000', '#aa00aa','#772277','#333333']
cols = ['#666666','#012345','#aa00aa','#bbaa00','#ee6600','#ff0000', '#00aaaa','#772277','#00cc00']
counter = -1
for igene in range(0,len(MT)):
spTimesThisGene = []
spTimesThisGene2 = []
ISIs_thisgene = []
for imut in range(0,len(MT[igene])):
spTimesThisMut = []
spTimesThisMut2 = []
ISIs_thismut = []
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
if exists('ifcurvesmut_cs'+str(icell)+'_'+str(igene)+'_'+str(imut)+'_'+str(iallmutval)+'.sav'):
continue
mutval = allmutvals[iallmutval]
nextCoeffs = [0.0,2.0,1.0]
spTimesThisVal = []
spTimesThisVal2 = []
ISIs_thismutval = []
close("all")
f, axarr = plt.subplots(1, 1)
axarr.set_position([0.13, 0.1, 0.85, 0.67])
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 + ", "
#else:
# mutText = mutText + "\n"
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
spTimesThisCoeff = []
spTimesThisCoeff2 = []
ISIs = len(Is)*[0.0]
nSpikes = []
for iI in range(0,len(Is)):
tstop = 8000.0
squareAmp = Is[iI]
squareDur = 7800.0
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)+"""
syn1.onset = 200 + """+str(BACdt)+"""
""")
h.init()
h.run()
times=np.array(h.tvec)
Vsoma=np.array(h.vsoma)
Vdend=np.array(h.vdend)
spikes = mytools.spike_times(times,Vsoma,-35,-45)
spikes2 = mytools.spike_times(times,Vsoma,-35,100)
spTimesThisCoeff.append(spikes[:])
spTimesThisCoeff2.append(spikes2[:])
nSpikes1 = len(spikes)
nSpikes2 = sum([1 for x in spikes if x >= 500.0])
nSpikes.append(nSpikes2)
if nSpikes1 > 5:
spts = spikes[len(spikes)-5:len(spikes)]
ISIs[iI] = mean([y-x for x,y in zip(spts[0:4],spts[1:5])])
else:
ISIs[iI] = 1.0e10
#if iter==0:
# #axarr.plot(Is, [1000.0/x for x in ISIs_control])
# axarr.plot(Is, [x/7.5 for x in nSpikes_control])
#axarr.plot(Is, [1000.0/x for x in ISIs], styles[iter],color=cols[iter])
axarr.plot(Is, [x/7.5 for x in nSpikes], styles[iter],color=cols[iter])
#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]])+"""
}""")
spTimesThisVal.append(spTimesThisCoeff[:])
spTimesThisVal2.append(spTimesThisCoeff2[:])
ISIs_thismutval.append(ISIs[:])
axarr.set_title('I-F curve')
xlabel('I (nA)')
ylabel('F (Hz)')
f.suptitle(mutText)
f.savefig("ifcurve_mutruns_cs"+str(icell)+"_"+str(igene)+"_"+str(imut)+"_"+str(iallmutval)+".eps")
spTimesThisMut.append(spTimesThisVal[:])
spTimesThisMut2.append(spTimesThisVal2[:])
ISIs_thismut.append(ISIs_thismutval[:])
picklelist = [ISIs_thismutval,spTimesThisVal,spTimesThisVal2,MT]
file = open('ifcurvesmut_cs'+str(icell)+'_'+str(igene)+'_'+str(imut)+'_'+str(iallmutval)+'.sav', 'w')
pickle.dump(picklelist,file)
file.close()
spTimesThisGene.append(spTimesThisMut[:])
spTimesThisGene2.append(spTimesThisMut2[:])
ISIs_thisgene.append(ISIs_thismut[:])
spTimesAll.append(spTimesThisGene[:])
spTimesAll2.append(spTimesThisGene2[:])
ISIs_all.append(ISIs_thisgene[:])
#picklelist = [ISIs_all,spTimesAll,spTimesAll2,MT]
#file = open('ifcurves_mut.sav', 'w')
#pickle.dump(picklelist,file)
#file.close()
ISIs_allAll.append(ISIs_all)
spTimesAllAll.append(spTimesAll)
spTimesAllAll2.append(spTimesAll2)
picklelist = [ISIs_allAll,spTimesAllAll,spTimesAllAll2,MT]
file = open('ifcurvesmut.sav', 'w')
pickle.dump(picklelist,file)
file.close()