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 mutation_stuff
MT = mutation_stuff.getMT()
defVals = mutation_stuff.getdefvals()
keyList = defVals.keys()
mySuffixes = mutation_stuff.getsuffixes()
mySuffixExceptions = mutation_stuff.getsuffixexceptions()
indIsLc = 2
nSpikesPerLc = 5
theseCoeffsAllAll = []
##squareAmps = [0.856,0,0.802]
##epsp_gmaxs = [0,0.0392,0.0367]
#squareAmps = [0.781,0,0.699]
#epsp_gmaxs = [0,0.0376,0.0337]
BACdt = 2.5
h("""
load_file("myrun.hoc")
objref cvode
cvode = new CVode()
cvode.active(1)
cvode.atol(0.001)
access a_soma
objref st1,syn1, sl
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+"""+str(BACdt)+"""
syn1.tau = 3
syn1.gmax = 0.005
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
tstop = 1000
""")
ITERS = 30
paramdicts = []
paramdicts.append({}) # 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
theseCoeffsAllAll = []
theseMutValsAllAll = []
theseMutVarsAllAll = []
for icell in range(0,len(paramdicts)):
paramdict = paramdicts[icell]
setparams(paramdict)
theseCoeffsAll = []
theseMutValsAll = []
theseMutVarsAll = []
unpicklefile = open('controlamps_cs'+str(icell)+'.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
mySquareAmpsAll = unpickledlist[0]
mySynAmpsAll = unpickledlist[1]
squareAmps = [mySquareAmpsAll[i][0][-1] for i in range(0,len(mySquareAmpsAll))]
synAmps = [mySynAmpsAll[i][0][-1] for i in range(0,len(mySynAmpsAll))]
squareDurs = [5,5,5]
unpicklefile = open('control_cs'+str(icell)+'.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
Is = [0.7,0.75,0.8,0.85]
Is_control = unpickledlist[19]
spikfreqs_control = mytools.interpolate(Is_control,unpickledlist[0],Is)
timesc_control = unpickledlist[1]
Vsomac_control = unpickledlist[2]
VDerivc_control = unpickledlist[3]
VDcoeff_control = unpickledlist[4][0]
counter = -1
for igene in range(0,len(MT)):
#for igene in range(0,1):
theseCoeffsGene = []
for imut in range(0,len(MT[igene])):
#for imut in range(0,1):
theseCoeffsMut = []
nVals = len(MT[igene][imut])*[0]
thesemutvars = []
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]]
theseMutValsAll.append(allmutvals[:])
theseMutVarsAll.append(allmutvars[:])
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('scalings_cs'+str(icell)+'_'+str(counter)+'.sav'):
continue
nextCoeffs = [0.0,2.0,1.0]
for iter in range(0,ITERS+2+3):
thisCoeff = nextCoeffs[min(iter,2)]
mutText = ""
for imutvar in range(0,len(MT[igene][imut])):
if imutvar > 0 and imutvar%2==0:
mutText = mutText+"\n"
mutvars = allmutvars[iallmutval][imutvar]
if type(mutvars) is str:
mutvars = [mutvars]
mutText = mutText + str(mutvars) + ": "
mutvals = allmutvals[iallmutval][imutvar]
#if type(mutvals) is list:
# mutvals = max([mutvals[max(range(len(mutvals)), key=lambda i: mutvals[i])],-mutvals[min(range(len(mutvals)), key=lambda i: mutvals[i])]])
for kmutvar in range(0,len(mutvars)):
if (mutvars[kmutvar].find('off') > -1 and mutvars[kmutvar].find('offc') < 0) or mutvars[kmutvar].find('eh') > -1:
newVal = defVals[mutvars[kmutvar]]+thisCoeff*mutvals
if mutvals >= 0 and kmutvar==0:
mutText = mutText + "+" + str(mutvals*thisCoeff) +" mV"
elif kmutvar==0:
mutText = mutText + str(mutvals*thisCoeff) +" mV"
else:
newVal = defVals[mutvars[kmutvar]]*(mutvals**thisCoeff)
if kmutvar==0:
mutText = mutText + "*" + str(mutvals**thisCoeff)
if kmutvar < len(mutvars)-1:
mutText = mutText + ", "
#else:
# mutText = mutText + "\n"
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
close("all")
f, axarr = plt.subplots(2, 4)
for ix in range(0,3):
for iy in range(0,2):
axarr[iy,ix].set_position([0.05+0.3*ix, 0.05+0.4*(1-iy), 0.23, 0.3])
tstop = 4000.0
ampCoeffs = [0.85,1.15]
isChanged = False
for icond in range(0,3):
############################################# Condition 1-3: Response to short stimuli #############################################
for iampCoeff in range(0,len(ampCoeffs)):
squareAmp = squareAmps[icond]*ampCoeffs[iampCoeff]
squareDur = squareDurs[icond]
epsp_gmax = synAmps[icond]*ampCoeffs[iampCoeff]
h("""
tstop = """+str(tstop)+"""
v_init = -62
cai0_ca_ion = """+str(thisCa)+"""
st1.amp = """+str(squareAmp)+"""
st1.del = 3400
st1.dur = """+str(squareDur)+"""
syn1.gmax = """+str(epsp_gmax)+"""
""")
h.init()
h.run()
times=np.array(h.tvec)
Vdend=np.array(h.vdend)
Vsoma=np.array(h.vsoma)
spikes = mytools.spike_times(times,Vsoma,-20,-45)
nSpikes1 = len(spikes)
print "icond="+str(icond)+",iamp="+str(iampCoeff)+", nSpikes1="+str(nSpikes1)+", st1.amp="+str(h.st1.amp)+", syn1.gmax="+str(h.syn1.gmax)
axarr[iampCoeff,icond].plot(times, Vsoma)
axarr[iampCoeff,icond].set_title("nspikes="+str(nSpikes1))
axarr[iampCoeff,icond].set_xlim([3390,3500])
axarr[iampCoeff,icond].set_ylim([-100,40])
f.savefig("testtesttest.png")
isChanged = isChanged or nSpikes1 > 0 and iampCoeff == 0 or nSpikes1 == 0 and iampCoeff == 1
print isChanged
if isChanged:
if iter==0:
print "Even null mutation causes different spiking!! igene="+str(igene)+", imut="+str(imut)+", iallmutval="+str(iallmutval)
nextCoeffs = [nextCoeffs[0],nextCoeffs[1],nextCoeffs[0]]
f.suptitle(mutText)
f.savefig("vrecs_mut"+str(igene)+"_"+str(imut)+"_"+str(iallmutval)+"_ITER"+str(iter)+".png")
break
if iter>=2 and iter < ITERS+2:
nextCoeffs = [nextCoeffs[0],nextCoeffs[2],0.5*nextCoeffs[0]+0.5*nextCoeffs[2]]
f.savefig("vrecs_mut"+str(igene)+"_"+str(imut)+"_"+str(iallmutval)+"_ITER"+str(iter)+".png")
continue
############################################# Condition 4: IF curve #############################################
spikfreqs = len(Is)*[0]
for iI in range(0,len(Is)):
tstop = 7200.0
squareAmp = Is[iI]
squareDur = 3800.0
epsp_gmax = 0.0
h("""
tstop = """+str(tstop)+"""
v_init = -62
cai0_ca_ion = """+str(thisCa)+"""
st1.amp = """+str(squareAmp)+"""
st1.dur = """+str(squareDur)+"""
syn1.gmax = """+str(epsp_gmax)+"""
""")
h.init()
h.run()
times=np.array(h.tvec)
Vsoma=np.array(h.vsoma)
spikes = mytools.spike_times(times,Vsoma,-20,-45)
spikfreqs[iI] = sum([1 for x in spikes if x >= 3700.0])/3.5
if iI==2: # use the memb. pot. time course of 0.8nA for the limit cycle
times_lc = times[:]
Vsoma_lc = Vsoma[:]
spikes_lc = spikes[:]
f2, axarr2 = subplots(1, 1)
axarr2.plot(times, Vsoma)
axarr2.set_title("Perisomatic firing, nspikes="+str(len(spikes))+", after 300ms nspikes="+str(sum([1 for x in spikes if x >= 3700.0])))
axarr2.set_ylim([-100,40])
axarr2.set_xlim([3390,7200])
f2.savefig("testscaling_"+str(iI)+".eps")
spikfreqdiffsum = sum([abs(x-y) for x,y in zip(spikfreqs,spikfreqs_control)])
spikfreqdiffrel = spikfreqdiffsum/sum(spikfreqs_control)
axarr[0,3].plot(Is, spikfreqs)
axarr[0,3].set_title("IF, diff="+str(spikfreqdiffrel))
axarr[0,3].set_xlim([0,1.25])
axarr[0,3].set_ylim([0,20])
############################################# Condition 5: Limit cycles ############################################
print "spikfreqdiffrel="+str(spikfreqdiffrel)
f.suptitle(mutText)
if iter < ITERS+2:
f.savefig("vrecs_mut"+str(igene)+"_"+str(imut)+"_"+str(iallmutval)+"_ITER"+str(iter)+".png")
else:
f.savefig("vrecs_mut"+str(igene)+"_"+str(imut)+"_"+str(iallmutval)+"_TEST"+str(iter-ITERS-2)+".png")
isChanged = isChanged or spikfreqdiffrel > 0.1
print isChanged
if iter==0 and isChanged:
print "Even null mutation causes different spiking!! igene="+str(igene)+", imut="+str(imut)+", iallmutval="+str(iallmutval)
nextCoeffs = [nextCoeffs[0],nextCoeffs[1],nextCoeffs[0]]
break
if iter==1 and not isChanged:
print "This mutation effect does not alter spiking even when doubled!! igene="+str(igene)+", imut="+str(imut)+", iallmutval="+str(iallmutval)
continue
if iter>=2 and iter < ITERS+2:
if isChanged:
nextCoeffs = [nextCoeffs[0],nextCoeffs[2],0.5*nextCoeffs[0]+0.5*nextCoeffs[2]]
else:
nextCoeffs = [nextCoeffs[2],nextCoeffs[1],0.5*nextCoeffs[1]+0.5*nextCoeffs[2]]
if iter == ITERS+1:
nextCoeffs = [nextCoeffs[2],nextCoeffs[2],nextCoeffs[2]*0.99]
if iter == ITERS+2:
nextCoeffs = [nextCoeffs[0],nextCoeffs[0],nextCoeffs[0]*1.0]
if iter == ITERS+3:
nextCoeffs = [nextCoeffs[0],nextCoeffs[0],nextCoeffs[0]*1.01]
#Restore default values:
for imutvar in range(0,len(MT[igene][imut])):
mutvars = allmutvars[iallmutval][imutvar]
if type(mutvars) is str:
mutvars = [mutvars]
mutvals = allmutvals[iallmutval][imutvar]
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]]))
theseCoeffsMut.append(nextCoeffs[0]+0.0)
picklelist = [nextCoeffs[0]+0.0,igene,imut,iallmutval,counter,MT]
file = open('scalings_cs'+str(icell)+'_'+str(counter)+'.sav', 'w')
pickle.dump(picklelist,file)
file.close()
theseCoeffsGene.append(theseCoeffsMut[:])
theseCoeffsAll.append(theseCoeffsGene[:])
theseCoeffsAllAll.append(theseCoeffsAll[:])
#picklelist = [theseCoeffsAllAll,theseMutVarsAll,theseMutValsAll,MT]
#file = open('scalings.sav', 'w')
#pickle.dump(picklelist,file)
#file.close()