from neuron import h
import matplotlib
matplotlib.use('Agg')
import numpy
from pylab import *
import mytools
import pickle
import time
import sys
import random
from setparams import *
import itertools
random.seed(1)
v0 = -80
ca0 = 0.0001
proximalpoint = 400
distalpoint = 620
fs = 8
ITERS = 20
tstop = 11000.0
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]
theseMutValsAllAll = unpickledlist[2]
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
#lensToStart = [100.0 + x*50 for x in range(0,16)]
lensToStart = [0.0, 200.0, 400.0, 600.0, 800.0, 1000.0]
lensToEnd = [200.0, 400.0, 600.0, 800.0, 1000.0, 1300.0]
lenToStartBasal = 0.0
lenToEndBasal = 282.0
gCoeffsAllAllAll = []
currCoeff = 0.5
if len(sys.argv) > 2:
currCoeff = float(sys.argv[2])
for icell in range(0,7):
gCoeffsAllAll = []
synlocsAllAll = []
Nsyns_all = []
for istartdist in range(0,len(lensToStart)):
lenToStart = lensToStart[istartdist]
lenToEnd = lensToEnd[istartdist]
unpicklefile = open('synlocs'+str(lenToStart)+'-'+str(lenToEnd)+'.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
Nsyns = unpickledlist[0]
synlocsAll = unpickledlist[3]
lenToStart = int(lenToStart)
lenToEnd = int(lenToEnd)
unpicklefile = open('thresholddistalamp'+str(lenToStart)+'-'+str(lenToEnd)+'_cs'+str(icell)+'_0.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
gsAll = unpickledlist[1]
Nsyns_all.append(Nsyns)
gCoeffsAllAll.append(gsAll[:])
synlocsAllAll.append(synlocsAll[:])
unpicklefile = open('basalsynlocs'+str(lenToStartBasal)+'-'+str(lenToEndBasal)+'.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
Nsyns = unpickledlist[0]
synlocsAll = unpickledlist[3]
unpicklefile = open('thresholdbasalamp0-282_cs'+str(icell)+'_0.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
gsAll = unpickledlist[1]
Nsyns_all.append(Nsyns)
gCoeffsAllAll.append(gsAll[:])
synlocsAllAll.append(synlocsAll[:])
coding_inputs = list(itertools.product([0, 1], repeat=7))
if len(sys.argv) > 3 and int(float(sys.argv[3])) != icell:
continue
morphology_file = "morphologies/cell1.asc"
biophys_file = "models/L5PCbiophys3.hoc"
template_file = "models/L5PCtemplate.hoc"
theseCoeffsAll = theseCoeffsAllAll[icell]
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
objref vsoma, vdend, recSite, vdends, isoma, cadends, casoma
vsoma = new Vector()
casoma = new Vector()
vdend = new Vector()
cadends = new List()
vdends = new List()
objref sl,st2,ns,syn1,con1,isyn, tvec, syns["""+str(7*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]
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
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)
""")
for idist in range(0,6):
h("""
cadends.append(new Vector())
vdends.append(new Vector())
sl = L5PC.locateSites("apic","""+str((lensToStart[idist]+lensToEnd[idist])*0.5)+""")
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]
cvode.record(&cai(siteVec[1]),cadends.o[cadends.count()-1],tvec)
cvode.record(&cai(siteVec[1]),vdends.o[vdends.count()-1],tvec)
""")
for istim in range(0,Nsyns):
h("""
siteVec[0] = """+str(synlocsAllAll[idist][0][istim][0])+"""
siteVec[1] = """+str(synlocsAllAll[idist][0][istim][1])+"""
access L5PC.apic[siteVec[0]]
L5PC.apic[siteVec[0]] {
syns["""+str(Nsyns*idist+istim)+"""] = new AlphaSynapse(siteVec[1])
syns["""+str(Nsyns*idist+istim)+"""].e = 0
syns["""+str(Nsyns*idist+istim)+"""].tau = 5
syns["""+str(Nsyns*idist+istim)+"""].onset = 10000
syns["""+str(Nsyns*idist+istim)+"""].gmax = """+str(gCoeffsAllAll[idist][0]*currCoeff)+"""
}
""")
for istim in range(0,Nsyns):
h("""
siteVec[0] = """+str(synlocsAllAll[6][0][istim][0])+"""
siteVec[1] = """+str(synlocsAllAll[6][0][istim][1])+"""
access L5PC.dend[siteVec[0]]
L5PC.dend[siteVec[0]] {
syns["""+str(Nsyns*6+istim)+"""] = new AlphaSynapse(siteVec[1])
syns["""+str(Nsyns*6+istim)+"""].e = 0
syns["""+str(Nsyns*6+istim)+"""].tau = 5
syns["""+str(Nsyns*6+istim)+"""].onset = 10000
syns["""+str(Nsyns*6+istim)+"""].gmax = """+str(gCoeffsAllAll[6][0]*currCoeff)+"""
}
""")
paramdict = paramdicts[icell]
setparams(paramdict)
styles = ['g-','g-','g-','g-','g-','g-','g-','g-','g-']
#cols = ['#aaffaa','#aaffaa','#66ff66','#66aaaa','#00aaaa','#00aaaa']
#cols = ['#00aaaa','#00bb77','#11cc44','#11dd11','#55ee00','#99dd00']
cols = ['#00aaaa','#11cc44','#55ee00','#bbaa00','#ee6600','#ff0000', '#aa00aa','#772277','#333333']
#yplus = [1, 2, 3, 4, 5, 6, -1, -2, -3]
#yplus = [x+3 for x in yplus]
yplus = [0, 0, 0, 0, 0, 0, 0, 0, 0]
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]]
counter = -1
for igene in range(0,len(MT)):
gCoeffsThisGene = []
for imut in range(0,len(MT[igene])):
gCoeffsThisMut = []
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
gCoeffsThisMutVal = []
close("all")
f, axarr = plt.subplots(2, 2)
maxCac = 0
maxCadc = 0
#for iter in [2, 5, 8, -1]:
iters = [0, 2, 6, 8, -1]
nspsThisVal = []
mytime = time.time()
coding_outputs = []
for iiter in range(0,len(iters)):
nspsThisIter = []
iter = iters[iiter]
gCoeffsThisIter = []
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!
if iter == 5:
continue
#thisg = gcoeffsAllAll[icell][igene][imut][iallmutval][iiter]
#print "iter="+str(iter)+", thisCoeff="+str(thisCoeff)+", thisg="+str(thisg)
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
thisCa = h.L5PC.soma[0].minCai_CaDynamics_E2
h("""
tstop = """+str(tstop)+"""
cai0_ca_ion = """+str(thisCa)+"""
v_init = """+str(v0)+"""
st1.amp = 0
st1.del = 200
st1.dur = 10
""")
coding_outputs_thisiter = []
for icoding in range(0,len(coding_inputs)):
for idist in range(0,6):
for istim in range(0,Nsyns):
h("syns["+str(Nsyns*idist+istim)+"].gmax = "+str(gCoeffsAllAll[idist][0]*currCoeff*coding_inputs[icoding][idist]))
print "syns["+str(Nsyns*idist)+"+istim].gmax = "+str(gCoeffsAllAll[idist][0]*currCoeff*coding_inputs[icoding][idist])
for istim in range(0,Nsyns):
h("syns["+str(Nsyns*6+istim)+"].gmax = "+str(gCoeffsAllAll[6][0]*currCoeff*coding_inputs[icoding][6]))
print "syns["+str(Nsyns*6)+"+istim].gmax = "+str(gCoeffsAllAll[6][0]*currCoeff*coding_inputs[icoding][6])
timenow = time.time()
h.init()
try:
h.run()
except RuntimeError:
hasErred = 1
print "Too large g!"
times=np.array(h.tvec)
Vsoma=np.array(h.vsoma)
spikes = mytools.spike_times(times,Vsoma,-20,-45)
nSpikes1 = len(spikes)
coding_outputs_thisiter.append([max(array(h.cadends)[i]) for i in range(0,6)]+[nSpikes1]+[max(array(h.vdends)[i]) for i in range(0,6)])
coding_outputs.append(coding_outputs_thisiter[:])
#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]])+"""
}""")
picklelist = [theseCoeffsAll,coding_inputs,coding_outputs,MT]
file = open('codings'+str(currCoeff)+'_cs'+str(icell)+'_'+str(counter)+'.sav', 'w')
pickle.dump(picklelist,file)
file.close()
print "codings done in "+str(time.time()-mytime)+" seconds, icell="+str(icell)+", igene="+str(igene)+", imut="+str(imut)+", iallmutval="+str(iallmutval)