from neuron import h
import matplotlib
matplotlib.use('Agg')
import numpy
from pylab import *
import mytools
import pickle
import time
import sys
import random

random.seed(1)

v0 = -80
ca0 = 0.0001
proximalpoint = 400
distalpoint = 620
BACdt = 5.0
fs = 8
xs = range(700,1150,50);
tstop = 11000.0
currCoeff = 0.9 # use the threshold current I*1.1 for inducing the first spike, and I*1.1*2 for the second spike 
ITERS = 20#
PPIdts = range(0,500,2)
#PPIdts = range(50,500,50)
maxLens = [1300,1185]

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]

unpicklefile = open('thresholddistalamp300_control.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
gs_control = unpickledlist[0]
Nsyns = unpickledlist[1]
maxSynsPerSeg = unpickledlist[2]

unpicklefile = open('thresholddistalamp300_cs.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
gsAllAll = unpickledlist[1]

unpicklefile = open('synlocs300.sav', 'r')
unpickledlist = pickle.load(unpicklefile)
unpicklefile.close()
synlocsAll = unpickledlist[3]

gCoeffsAllAll = []

for icell in range(0,1):
  gsAll = gsAllAll[icell]
  synlocs = synlocsAll[icell]
  morphology_file = "morphologies/cell"+str(icell+1)+".asc"
  biophys_file = "models/L5PCbiophys3.hoc"
  template_file = "models/L5PCtemplate.hoc"

  theseCoeffsAll = theseCoeffsAllAll[icell]

  gCoeffsAll = []

  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
forsec L5PC.somatic {
}
forsec L5PC.apical {
}
L5PC.distribute_channels("apic","gIhbar_Ih",2,-0.8696,3.6161,0.0,1.0*2.0870,0.0002)
L5PC.distribute_channels("apic","gCa_HVAbar_Ca_HVA",3,1.0,0.1,685.0,885.0,1.0*0.000555)
L5PC.distribute_channels("apic","gCa_LVAstbar_Ca_LVAst",3,1.0,0.01,685.0,885.0,1.0*0.0187)
objref vsoma, vdend, recSite, vdend2, isoma, cadend, cadend2, casoma
vsoma = new Vector()
casoma = new Vector()
vdend = new Vector()
cadend = new Vector()
vdend2 = new Vector()
cadend2 = new Vector()
objref sl,st2,ns,syn1,syn2,con1,isyn, tvec, syns["""+str(2*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]
print "distalpoint gCa_HVA: ", L5PC.apic[siteVec[0]].gCa_HVAbar_Ca_HVA
print "distalpoint gCa_LVA: ", L5PC.apic[siteVec[0]].gCa_LVAstbar_Ca_LVAst
access L5PC.apic[siteVec[0]]
cvode.record(&v(siteVec[1]),vdend,tvec)
cvode.record(&cai(siteVec[1]),cadend,tvec)
st2 = new IClamp(siteVec[1])
st2.amp = 0
L5PC.apic[siteVec[0]] {
  st2
  syn1 = new epsp(siteVec[1])
  syn1.tau0 = 0.5
  syn1.tau1 = 5
  syn1.onset = 145 + """+str(BACdt)+""" 
  syn1.imax = 0
  syn2 = new epsp(siteVec[1])
  syn2.tau0 = 0.5
  syn2.tau1 = 5
  syn2.onset = 145 + """+str(BACdt)+""" 
  syn2.imax = 0
  cvode.record(&syn1.i,isyn,tvec)
}
access L5PC.soma
cvode.record(&v(0.5),vsoma,tvec)
cvode.record(&cai(0.5),casoma,tvec)
""")
  for istim in range(0,Nsyns):
    h("""
siteVec[0] = """+str(synlocs[istim][0])+"""
siteVec[1] = """+str(synlocs[istim][1])+"""
access L5PC.apic[siteVec[0]]
L5PC.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 + """+str(BACdt)+"""
  syns["""+str(istim+Nsyns)+"""] = new AlphaSynapse(siteVec[1])
  syns["""+str(istim+Nsyns)+"""].e = 0
  syns["""+str(istim+Nsyns)+"""].tau = 5
  syns["""+str(istim+Nsyns)+"""].onset = 10000 + """+str(BACdt)+"""
}
""")

  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)):
   gsThisGene = gsAll[igene]
   gCoeffsThisGene = []
   for imut in range(0,len(MT[igene])): 
    gsThisMut = gsThisGene[imut]
    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]):
      gsThisMutVal = gsThisMut[iallmutval]
      gCoeffsThisMutVal = []
      counter = counter + 1                                                                                                                                                               
      if len(sys.argv) > 1 and int(float(sys.argv[1])) != counter:
        continue
      close("all")
      f, axarr = plt.subplots(4, 1)
      iters = [0, 2, 5, 6, 8, -1]
      for iiter in range(0,len(iters)):
        iter = iters[iiter]
        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:
          gCoeffsThisMutVal.append([])
          continue
        print "iter="+str(iter)+", thisCoeff="+str(thisCoeff)
        gsThisIter = gsThisMutVal[iiter]
        gCoeffsThisIter = []
        
        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
        for iPPI in range(0,len(PPIdts)):
          PPIdt = PPIdts[iPPI]

          nextCoeffs = [0,10.0,5.0]
          hasSpiked = 0
          for iterI in range(0,ITERS+2):
            for istim in range(0,Nsyns):
              h("syns["+str(istim)+"].gmax = "+str(gsThisIter*currCoeff))
              h("syns["+str(istim+Nsyns)+"].gmax = "+str(gsThisIter*currCoeff*nextCoeffs[min(iterI,2)]))
              h("syns["+str(istim+Nsyns)+"].onset = "+str(10000+BACdt+PPIdt))
            h("""
tstop = """+str(tstop)+"""
cai0_ca_ion = """+str(thisCa)+"""
v_init = """+str(v0)+"""
st1.amp = 0
st1.del = 200
st1.dur = 10
""")
            h.init()
            try:
              h.run()
            except RuntimeError:
              print "Too large I!"
              if iterI > 1:
                nextCoeffs = [nextCoeffs[0],nextCoeffs[2],0.5*(nextCoeffs[0]+nextCoeffs[2])]
              continue
            times=np.array(h.tvec)
            Casoma=np.array(h.casoma)
            Cadend=np.array(h.cadend)
            Vsoma=np.array(h.vsoma)
            Vdend=np.array(h.vdend)
            nSpikes_total = len(mytools.spike_times(times,Vsoma,-35,-37.5))
            print "nextCoeffs="+str(nextCoeffs)+", "+str(nSpikes_total)+" spikes"
            if iterI==0:
              nSpikes_normal = nSpikes_total
            hasSpiked = hasSpiked or (nSpikes_total > nSpikes_normal)
            if iterI > 0 and not hasSpiked:
              nextCoeffs = [nextCoeffs[1],2*nextCoeffs[1],1.5*nextCoeffs[1]]
              continue
            if iterI > 1 and nSpikes_total > nSpikes_normal:
              nextCoeffs = [nextCoeffs[0],nextCoeffs[2],0.5*(nextCoeffs[0]+nextCoeffs[2])]
            if iterI > 1 and nSpikes_total <= nSpikes_normal:
              nextCoeffs = [nextCoeffs[2],nextCoeffs[1],0.5*(nextCoeffs[2]+nextCoeffs[1])]
            #print str(nSpikes_total)+", nextCoeffs="+str(nextCoeffs)

          gCoeffsThisIter.append(nextCoeffs[2])

        #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]])+"""
}""")
        gCoeffsThisMutVal.append(gCoeffsThisIter[:])

        if iter==-1:
          picklelist = [theseCoeffsAllAll,gsAllAll,PPIdts,gCoeffsThisIter,MT]
          file = open('ppispthrcoeff300_relthr_cs'+str(icell)+'_control.sav', 'w')
          pickle.dump(picklelist,file)
          file.close()

      gCoeffsThisMut.append(gCoeffsThisMutVal[:])

      picklelist = [theseCoeffsAllAll,gsAllAll,PPIdts,gCoeffsThisMutVal,MT]
      file = open('ppispthrcoeff300_relthr_scaledonly_cs'+str(icell)+'_'+str(counter)+'.sav', 'w')
      pickle.dump(picklelist,file)
      file.close()
    gCoeffsThisGene.append(gCoeffsThisMut[:])
  
   gCoeffsAll.append(gCoeffsThisGene[:])

  gCoeffsAllAll.append(gCoeffsAll[:])
  #file = open('ppis.sav', 'w')
  #pickle.dump(picklelist,file)
  #file.close()
#picklelist = [PPIdts,CasomasAllAll,VsomasAllAll,CadendsAllAll,CadendsAllAll,timesAllAll,CasomaAmpsAllAll,CadendAmpsAllAll,VsomaAmpsAllAll,VdendAmpsAllAll,MT]
#file = open('ppispthrcoeff300_relthr_cs.sav', 'w')
#pickle.dump(picklelist,file)
#file.close()