#hoc-code based on implementation https://senselab.med.yale.edu/modeldb/showModel.cshtml?model=151825
#(CC BY 3.0) Tuomo Maki-Marttunen
from neuron import h
import matplotlib
matplotlib.use('Agg')
import numpy
from pylab import *
import mytools
import pickle
import sys
v0 = -62
ca0 = 0.0001
proximalpoint = 400
distalpoint = 620
#distalpoint = 960
BACdt = 5.0
Is = [0.65+0.025*x for x in range(0,11)]
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()
defVals = mutation_stuff.getdefvals()
keyList = defVals.keys()
mySuffixes = mutation_stuff.getsuffixes()
mySuffixExceptions = mutation_stuff.getsuffixexceptions()
unpicklefile = open('scalings.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
theseCoeffsAll = unpickledlist[0]
theseMutValsAll = unpickledlist[2]
for icell in range(0,1):
threshIsAll = []
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
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
tstop = 1000
""")
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']
counter = -1
for igene in range(0,len(MT)):
threshIsThisGene = []
for imut in range(0,len(MT[igene])):
threshIsThisMut = []
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
mutval = allmutvals[iallmutval]
threshIsThisVal = []
close("all")
f, axarr = plt.subplots(1, 1)
axarr.set_position([0.13, 0.1, 0.85, 0.67])
for iter in [0, 2, 5, 6, 8, -1]:
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!
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 (mutvars[kmutvar].find('off') > -1 and mutvars[kmutvar].find('offc') < 0) or mutvars[kmutvar].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
threshIsThisCoeff = []
nSpikes = []
ITERS = 25
nextIs = [0.4,0.6,0.80]
for iITER in range(0,ITERS+2):
tstop = 1000.0
squareAmp = nextIs[min(iITER,2)]
squareDur = 800.0
h("""
tstop = """+str(tstop)+"""
v_init = """+str(v0)+"""
cai0_ca_ion = """+str(thisCa)+"""
st1.amp = """+str(squareAmp)+"""
st1.del = 200
st1.dur = """+str(squareDur)+"""
syn1.gmax = 0
syn1.onset = 200 + """+str(BACdt)+"""
""")
h.init()
h.run()
times=np.array(h.tvec)
Vsoma=np.array(h.vsoma)
Vdend=np.array(h.vdend)
spikes = mytools.spike_times(times,Vsoma,-50,-50)
spikes2 = mytools.spike_times(times,Vsoma,-50,inf)
nSpikes2 = sum([1 for x in spikes if x >= 0.0])
isChanged = nSpikes2 > 0
print str(nSpikes2)+" spikes, I="+str(squareAmp)
if iITER==0 and isChanged:
print "Even zero amplitude causes spiking!! igene="+str(igene)+", imut="+str(imut)+", iallmutval="+str(iallmutval)
continue
if iITER==1 and not isChanged:
print "Even large current does not cause spiking!! igene="+str(igene)+", imut="+str(imut)+", iallmutval="+str(iallmutval)
continue
if iITER>=2 and iITER < ITERS+2:
if isChanged:
nextIs = [nextIs[0],nextIs[2],0.5*nextIs[0]+0.5*nextIs[2]]
else:
nextIs = [nextIs[2],nextIs[1],0.5*nextIs[1]+0.5*nextIs[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]]))
threshIsThisVal.append(nextIs[2])
threshIsThisMut.append(threshIsThisVal[:])
picklelist = [threshIsThisVal,MT]
file = open('DCshortthreshs_'+str(igene)+'_'+str(imut)+'_'+str(iallmutval)+'.sav', 'w')
pickle.dump(picklelist,file)
file.close()
threshIsThisGene.append(threshIsThisMut[:])
threshIsAll.append(threshIsThisGene[:])