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 *
from os.path import exists
random.seed(1)
v0 = -62
ca0 = 0.0001
proximalpoint = 400
distalpoint = 620
fs = 8
ITERS = 30
tstop = 11000.0
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_cs.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
theseCoeffsAllAll = unpickledlist[0]
theseMutValsAllAll = unpickledlist[2]
paramdicts = []
paramdicts.append({'transvec.x(31)': 1.0, 'transvec.x(32)': 1.0, 'transvec.x(20)': 1.0, 'transvec.x(21)': 1.0, 'transvec.x(25)': 1.0, 'transvec.x(26)': 1.0}) # 4-6 spikes per burst, control
paramdicts.append({'transvec.x(31)': 1.25, 'transvec.x(32)': 1.25}) # 4-5 spikes per burst
paramdicts.append({'transvec.x(31)': 1.5, 'transvec.x(32)': 1.5}) # 3-4 spikes per burst
paramdicts.append({'transvec.x(31)': 2.0, 'transvec.x(32)': 2.0}) # 3-4 spikes per burst
paramdicts.append({'transvec.x(31)': 4.0, 'transvec.x(32)': 4.0}) # 2-3 spikes per burst
paramdicts.append({'transvec.x(31)': 4.0, 'transvec.x(32)': 4.0, 'transvec.x(20)': 1.3, 'transvec.x(21)': 1.3, 'transvec.x(25)': 1.3, 'transvec.x(26)': 1.3}) # 2 spikes per burst
paramdicts.append({'transvec.x(31)': 4.0, 'transvec.x(32)': 4.0, 'transvec.x(20)': 1.6, 'transvec.x(21)': 1.6, 'transvec.x(25)': 1.6, 'transvec.x(26)': 1.6}) # 1-2 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 = [100.0 + x*50 for x in range(0,16)]
lensToStart = [150.0, 300.0, 450.0, 600.0]
ISIs = [10.0*x for x in range(0,51)]
currCoeff = 1.1
gCoeffsAllAllAll = []
for istartdist in range(0,len(lensToStart)):
startdist = lensToStart[istartdist]
if len(sys.argv) > 2 and int(float(sys.argv[2])) != istartdist:
continue
unpicklefile = open('synlocs'+str(startdist)+'.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
Nsyns = unpickledlist[0]
synlocs = unpickledlist[3]
startdist = int(startdist)
unpicklefile = open('thresholddistalamp'+str(startdist)+'.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
gsAllAll = unpickledlist[1]
gCoeffsThisMut = []
for icell in range(0,7):
theseCoeffsAll = theseCoeffsAllAll[icell]
gCoeffsAll = []
if len(sys.argv) > 3 and int(float(sys.argv[3])) != icell:
continue
unpicklefile = open('thresholddistalamp'+str(startdist)+'_cs'+str(icell)+'_comb'+str(icomb)+'.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
gs_thiscomb = unpickledlist[1]
h("""
load_file("myrun.hoc")
objref cvode
cvode = new CVode()
cvode.active(1)
cvode.atol(0.001)
access a_soma
objref st1,syn1, sl, syns["""+str(2*Nsyns)+"""]
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, tvec
vsoma = new Vector()
vdend = new Vector()
tvec = new Vector()
a_soma cvode.record(&v(0.5),vsoma,tvec)
apic[siteVec[0]] cvode.record(&v(siteVec[1]),vdend,tvec)
v_init = -62
dt = 0.025
""")
paramdict = paramdicts[icell]
setparams(paramdict)
for istim in range(0,Nsyns):
h("""
siteVec[0] = """+str(synlocs[istim][0])+"""
siteVec[1] = """+str(synlocs[istim][1])+"""
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
syns["""+str(Nsyns+istim)+"""] = new AlphaSynapse(siteVec[1])
syns["""+str(Nsyns+istim)+"""].e = 0
syns["""+str(Nsyns+istim)+"""].tau = 5
syns["""+str(Nsyns+istim)+"""].onset = 10000
}
""")
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]]
mytime = time.time()
iitercounter = -1
gCoeffsThisMutVal = []
for iter in [0, 2, 6, 8, -1]:
iitercounter = iitercounter + 1
defVals = mutation_stuff.getdefvals()
keyList = defVals.keys()
gCoeffsThisIter = []
thisg = gs_thiscomb[iitercounter][-1]
if iter == 5:
continue
counter = -1
if exists('PPIcoeffs'+str(startdist)+'_cs'+str(icell)+'_comb'+str(icomb)+'_iter'+str(iter)+'.sav'):
print 'PPIcoeffs'+str(startdist)+'_cs'+str(icell)+'_comb'+str(icomb)+'_iter'+str(iter)+'.sav exists, continuing'
continue
if len(sys.argv) > 4 and int(float(sys.argv[4])) != iter:
continue
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:
maxCac = 0
maxCadc = 0
if iter >= 0:
thisCoeff = coeffCoeffs[iter][0]*theseCoeffs[iallmutval] + coeffCoeffs[iter][1]*(1.0 - 0.5*theseCoeffs[iallmutval])
else:
thisCoeff = 0
if iter == 5:
gCoeffsThisIter.append([])
continue
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('off') > -1 and mutvar.find('offc') < 0) or mutvar.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
thisCa = h.a_soma.cainf_cad
for iISI in range(0,len(ISIs)):
gCoeffsThisISI = []
PPIdt = ISIs[iISI]
nextCoeffs = [0,15.0,4.0]
hasSpiked = 0
for iterI in range(0,ITERS+2):
for istim in range(0,Nsyns):
h("syns["+str(istim)+"].gmax = "+str(thisg*currCoeff))
h("syns["+str(Nsyns+istim)+"].gmax = "+str(thisg*currCoeff*nextCoeffs[min(iterI,2)]))
h("syns["+str(Nsyns+istim)+"].onset = "+str(10000+PPIdt))
h("""
tstop = """+str(tstop)+"""
cai0_ca_ion = """+str(thisCa)+"""
v_init = """+str(v0)+"""
st1.amp = 0
st1.del = 0
st1.dur = 0
""")
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,-50,-50)
nSpikes1 = len(spikes)
print "nextCoeffs="+str(nextCoeffs)+", "+str(nSpikes1)+" spikes, simulation done in "+str(time.time()-timenow)+" seconds"
#if iterI==0:
#nSpikes_normal = 1
nSpikes_normal = 1 + (icell<=2 and startdist<=400 or icell==3 and startdist<=300 or icell==4 and startdist<=250)
hasSpiked = hasSpiked or (nSpikes1 > nSpikes_normal)
if iterI == 0 and hasSpiked:
print "istartdist="+str(istartdist)+", icell="+str(icell)+", igene="+str(igene)+", imut="+str(imut)+", iallmuval="+str(iallmutval)+", iiter="+str(iitercounter)+": extra spikes elicited for iterI=0!"
if iterI > 0 and not hasSpiked:
print "istartdist="+str(istartdist)+", icell="+str(icell)+", igene="+str(igene)+", imut="+str(imut)+", iallmuval="+str(iallmutval)+", iiter="+str(iitercounter)+": no extra spikes for iterI>0!"
nextCoeffs = [nextCoeffs[1],2*nextCoeffs[1],1.5*nextCoeffs[1]]
continue
if iterI > 1 and nSpikes1 > nSpikes_normal:
nextCoeffs = [nextCoeffs[0],nextCoeffs[2],0.5*(nextCoeffs[0]+nextCoeffs[2])]
if iterI > 1 and nSpikes1 <= nSpikes_normal:
nextCoeffs = [nextCoeffs[2],nextCoeffs[1],0.5*(nextCoeffs[2]+nextCoeffs[1])]
#print str(nSpikes1)+", nextCoeffs="+str(nextCoeffs)
gCoeffsThisISI = nextCoeffs[:]
gCoeffsThisIter.append(gCoeffsThisISI[:])
defVals = mutation_stuff.getdefvals()
keyList = defVals.keys()
#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]]))
gCoeffsThisMutVal.append(gCoeffsThisIter[:])
picklelist = [theseCoeffsAll,gCoeffsThisMutVal,ISIs,MT]
file = open('PPIcoeffs'+str(startdist)+'_cs'+str(icell)+'_comb'+str(icomb)+'_iter'+str(iter)+'.sav', 'w')
pickle.dump(picklelist,file)
file.close()
gCoeffsThisMut.append(gCoeffsThisMutVal[:])