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
BACdt = 5.0
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
startdist = 0.0
enddist = 356.0
unpicklefile = open('basalsynlocs'+str(startdist)+'-'+str(enddist)+'.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
Nsyns = unpickledlist[0]
synlocs = unpickledlist[3]
gsAllAll = []
for icell in range(0,7):
gsAll = []
theseCoeffsAll = theseCoeffsAllAll[icell]
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(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])+"""
dend[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)+"""
}
""")
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)):
gsThisGene = []
for imut in range(0,len(MT[igene])):
gsThisMut = []
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
gsThisMutVal = []
minNSpikesThisMutVal = []
close("all")
f, axarr = plt.subplots(2, 2)
maxCac = 0
maxCadc = 0
if exists('thresholdbasalamp'+str(startdist)+'-'+str(enddist)+'_cs'+str(icell)+'_'+str(counter)+'.sav'):
print 'thresholdbasalamp'+str(startdist)+'-'+str(enddist)+'_cs'+str(icell)+'_'+str(counter)+'.sav exists, continuing'
continue
for iter in [0, 2, 5, 6, 8, -1]:
gsThisIter = []
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!
print "iter="+str(iter)+", thisCoeff="+str(thisCoeff)
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
nextgs = [0.00,0.003,0.0015]
hasSpiked = 0
hasErred = 0
minNSpikes = inf
for iterg in range(0,ITERS+2):
thisg = nextgs[min(iterg,2)]
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 = 0
st1.dur = 0
""")
h.init()
try:
h.run()
except RuntimeError:
hasErred = 1
print "Too large g!"
if iterg == 1:
nextgs = [0.0,0.0015,0.00075]
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,-50,-50)
nSpikes1 = len(spikes)
hasSpiked = hasSpiked or (nSpikes1 > 0)
if nSpikes1 > 0 and nSpikes1 < minNSpikes:
minNSpikes = nSpikes1
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)+", spike at "+str(spikes[0])
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[min(iterg,2)]]
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]]
#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]]))
gsThisMutVal.append(nextgs[2])
minNSpikesThisMutVal.append(minNSpikes)
gsThisMut.append(gsThisMutVal[:])
picklelist = [theseCoeffsAll,gsThisMutVal,minNSpikesThisMutVal,MT]
file = open('thresholdbasalamp'+str(startdist)+'-'+str(enddist)+'_cs'+str(icell)+'_'+str(counter)+'.sav', 'w')
pickle.dump(picklelist,file)
file.close()
gsThisGene.append(gsThisMut[:])
gsAll.append(gsThisGene[:])
gsAllAll.append(gsAll[:])
#picklelist = [theseCoeffsAll,gsThisAll,MT]
#file = open('thresholdbasalamp'+str(startdist)+'_'+str(counter)+'.sav', 'w')
#pickle.dump(picklelist,file)
#file.close()