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
import random
import time
v0 = -80
ca0 = 0.0001
proximalpoint = 400
distalpoint = 620
#distalpoint = 960
BACdt = 5.0
Is = unique([0.34+0.0025*x for x in range(0,11)]+[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()
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]
ITERS = 30
tstop = 11000.0
paramdicts = []
paramdicts.append({'A_gNaTa_tbar_NaTa_t': 1.0, 'S_gCa_HVAbar_Ca_HVA': 1.0}) # 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
icomb = 0
#combs_all = [ [[0,5,1], [1,2,15], [2,4,7], [3,1,0], [5,0,0], [8,5,0], [13,2,0]], #max, Hay cell 0
# [[0,5,0], [1,3,0], [2,5,1], [3,1,1], [6,3,0], [8,3,0], [12,1,1], [13,5,0]], #min, Hay cell 0
# [[0,5,1], [1,2,15], [2,4,7], [3,1,0], [5,0,0], [8,5,0], [13,3,0]], #max, Hay cell 1
# [[0,5,0], [1,3,0], [2,5,1], [3,1,1], [6,3,0], [8,3,0], [12,1,1], [13,5,0]], #min, Hay cell 1
# [[0,5,1], [1,2,15], [2,4,7], [3,1,0], [5,0,0], [8,5,0], [13,2,0]], #max, Hay cell 2
# [[0,5,0], [1,3,0], [2,5,1], [3,1,1], [6,3,0], [8,3,0], [12,1,1], [13,5,0]], #min, Hay cell 2
# [[0,5,1], [1,2,15], [2,4,7], [3,1,1], [5,0,0], [8,5,0], [13,5,0]], #max, Hay cell 3
# [[0,5,0], [1,3,0], [2,5,1], [3,0,1], [6,3,0], [8,3,0], [12,1,1], [13,4,0]], #min, Hay cell 3
# [[0,5,1], [1,2,15], [2,4,7], [3,1,1], [5,0,0], [8,5,0], [13,1,0]], #max, Hay cell 4
# [[0,5,0], [1,3,0], [2,5,1], [3,0,1], [6,3,0], [8,3,0], [12,1,1], [13,5,0]], #min, Hay cell 4
# [[0,5,1], [1,2,15], [2,4,7], [3,1,1], [5,0,0], [8,5,0], [13,5,0]], #max, Hay cell 5
# [[0,5,0], [1,3,0], [2,5,1], [3,0,1], [6,3,0], [8,3,0], [12,1,1], [13,3,0]], #min, Hay cell 5
# [[0,5,1], [1,2,15], [2,4,7], [3,1,1], [5,0,0], [8,5,0], [13,0,0]], #max, Hay cell 6
# [[0,5,0], [1,3,0], [2,5,1], [3,0,1], [6,3,0], [8,3,0], [12,1,1], [13,5,0]] ] #min, Hay cell 6
combs_all = [ [[0,2,9], [1,2,9], [2,4,1], [3,1,0], [5,0,0], [8,5,0], [13,0,0]], #max, Hay cell 0
[[0,2,4], [1,2,8], [2,5,0], [3,0,0], [6,0,0], [8,2,0], [12,1,1], [13,5,0]], #min, Hay cell 0
[[0,4,5], [1,2,3], [2,1,7], [3,0,1], [5,0,0], [8,2,0], [12,1,1]], #max, Almog cell 0
[[0,3,2], [1,2,14], [2,4,4], [3,1,0], [6,1,0], [8,5,0], [12,0,0], [13,5,0]] ]
if len(sys.argv) > 1:
icomb = int(float(sys.argv[1]))
combs = combs_all[icomb]
lensToStart = [300.0]
for istartdist in range(0,len(lensToStart)):
startdist = lensToStart[istartdist]
unpicklefile = open('synlocs'+str(startdist)+'.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
Nsyns = unpickledlist[0]
synlocsAll = unpickledlist[3]
startdist = int(startdist)
maxLens = [1300,1185]
gsAllAll = []
for icell in range(0,7):
synlocs = synlocsAll[0]
gsAll = []
theseCoeffsAll = theseCoeffsAllAll[icell]
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 vsoma, vdend, recSite, vdend2, isoma, cadend, cadend2, casoma
vsoma = new Vector()
casoma = new Vector()
vdend = new Vector()
cadend = new Vector()
objref sl,st2,ns,syn1,con1,isyn, tvec, syns["""+str(Nsyns)+"""]
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.imax = 0
syn1.tau1 = 5
syn1.onset = 145 + """+str(BACdt)+"""
cvode.record(&syn1.i,isyn,tvec)
}
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)
""")
for istim in range(0,Nsyns):
h("""
siteVec[0] = """+str(synlocs[istim][0])+"""
siteVec[1] = """+str(synlocs[istim][1])+"""
access L5PC.apic[siteVec[0]]
L5PC.apic[siteVec[0]] {
syns["""+str(istim)+"""] = new AlphaSynapse(siteVec[1])
syns["""+str(istim)+"""].e = 0
syns["""+str(istim)+"""].tau = 5
syns["""+str(istim)+"""].onset = 10000 + """+str(BACdt)+"""
}
""")
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']
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]
gsThisVal = []
for iter in [0, 2, 5, 6, 8, -1]:
counter = -1
for igene in range(0,len(MT)):
for imut in range(0,len(MT[igene])):
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
isin = False
for checkcomb in combs:
if igene == checkcomb[0] and imut == checkcomb[1] and iallmutval == checkcomb[2]:
isin = True
if isin:
mutval = allmutvals[iallmutval]
nextCoeffs = [0.0,2.0,1.0]
if iter >= 0:
thisCoeff = coeffCoeffs[iter][0]*theseCoeffs[iallmutval] + coeffCoeffs[iter][1]*(1.0 - 0.5*theseCoeffs[iallmutval])
else:
thisCoeff = 0
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]]
defVals[mutvar] = [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]]
defVals[mutvar] = [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
thisCa = h.L5PC.soma[0].minCai_CaDynamics_E2
nextgs = [0.00,0.003,0.0015]
hasSpiked = 0
hasErred = 0
for iterg in range(0,ITERS+2):
thisg = nextgs[min(iterg,2)]
h("st1.amp = "+str(thisg))
for istim in range(0,Nsyns):
h("syns["+str(istim)+"].gmax = "+str(thisg))
h("""
tstop = """+str(tstop)+"""
cai0_ca_ion = """+str(thisCa)+"""
v_init = """+str(v0)+"""
st1.amp = 0
st1.del = 200
st1.dur = 10
""")
h.init()
try:
h.run()
except RuntimeError:
hasErred = 1
print "Too large g!"
if iterg == 1:
nextgs = [0.0,4.0,3.0]
continue
else:
nextgs = [nextgs[0],nextgs[2],nextgs[0]+nextgs[2]]
continue
times=np.array(h.tvec)
Vsoma=np.array(h.vsoma)
spikes = mytools.spike_times(times,Vsoma,-20,-45)
nSpikes1 = len(spikes)
hasSpiked = hasSpiked or (nSpikes1 > 0)
print "iterg="+str(iterg)+" done, g="+str(thisg)+", "+str(nSpikes1)+" spikes"
if iterg==0 and nSpikes1 > 0:
print "Even zero g causes spiking!! igene="+str(igene)+", imut="+str(imut)+", iallmutval="+str(iallmutval)+", iter="+str(iter)
nextgs = [0.0,0.0,0.0]
break
if iterg==1 and not hasSpiked:
print "No spiking with iterg==1, adding 900% to the current! igene="+str(igene)+", imut="+str(imut)+", iallmutval="+str(iallmutval)
nextgs = [nextgs[0],10.0*nextgs[1],5*nextgs[1]]
continue
if iterg>=2 and iterg < ITERS+2:
if nSpikes1 > 0:
nextgs = [nextgs[0],nextgs[2],0.5*nextgs[0]+0.5*nextgs[2]]
else:
nextgs = [nextgs[2],nextgs[1],0.5*nextgs[1]+0.5*nextgs[2]]
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]
#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]])+"""
}""")
gsThisVal.append(nextgs[2])
picklelist = [theseCoeffsAll,gsThisVal,MT]
file = open('thresholddistalamp'+str(startdist)+'_cs'+str(icell)+'_comb'+str(icomb)+'.sav', 'w')
pickle.dump(picklelist,file)
file.close()