#Changed from _old4: Made high resolution (smaller CVode tolerance) 26.10.2016. Only do cells 0 and 1. 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 = -80 ca0 = 0.0001 #proximalpoints = [100,100,100,200,200,200,300,300,300,400,400,400] #distalpoints = [600,750,900,600,750,900,600,750,900,600,750,900] proximalpoints = [200,200] distalpoints = [600,850] BACdt = 5.0 fs = 8 tstop = 5000.0 #epspdts = [0.25*x for x in range(-80,81)] #epspdts = [0.5*x for x in range(-40,41)] epspdts = [4.0*x for x in range(-40,-20)]+[2.0*x for x in range(-40,-20)]+[1.0*x for x in range(-40,-20)]+[0.5*x for x in range(-40,41)]+[1.0*x for x in range(21,41)]+[2.0*x for x in range(21,41)]+[4.0*x for x in range(21,41)] epspdts_savetimecourses = [-40,-20,-15,-10,-5,0,5,10,15,20,40] Is_st2 = 1.32 st2coeff = 0.40 #Somatic 5ms pulse st2coeff_down = 1.35 #Somatic 5ms pulse st1coeff = 0.85 #Proximal apical 200ms pulse unpicklefile = open('apicalthresholds.sav', 'r') unpickledlist = pickle.load(unpicklefile) unpicklefile.close() IsAllAll_st1 = unpickledlist[0] dists = unpickledlist[1] unpicklefile = open('apicalthresholds_epsp.sav', 'r') unpickledlist = pickle.load(unpicklefile) unpicklefile.close() IsAllAll_syn1 = unpickledlist[0] 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] paramdicts = [] paramdicts.append({'A_gNaTa_tbar_NaTa_t': 1.0, 'S_gCa_HVAbar_Ca_HVA': 1.0}) # 1 spike per burst, control paramdicts.append({'A_gNaTa_tbar_NaTa_t': 1.6}) # 1-2 spikes per burst paramdicts.append({'A_gNaTa_tbar_NaTa_t': 2.2}) # 2-3 spikes per burst paramdicts.append({'A_gNaTa_tbar_NaTa_t': 2.2, 'S_gCa_HVAbar_Ca_HVA': 0.9}) # 3-4 spikes per burst paramdicts.append({'A_gNaTa_tbar_NaTa_t': 2.2, 'S_gCa_HVAbar_Ca_HVA': 0.625}) # 3-5 spikes per burst paramdicts.append({'A_gNaTa_tbar_NaTa_t': 2.2, 'S_gCa_HVAbar_Ca_HVA': 0.5}) # 4-6 spikes per burst paramdicts.append({'A_gNaTa_tbar_NaTa_t': 2.2, 'S_gCa_HVAbar_Ca_HVA': 0.3}) # 5-9 spikes per burst VsomaupAllAll = [] VsomadownAllAll = [] VdendupAllAll = [] VdenddownAllAll = [] counter = -1 for icell in range(0,7): syn1coeff = 0.5 - 0.35*(icell > 1) #Synaptic epsp-like input morphology_file = "morphologies/cell1.asc" biophys_file = "models/L5PCbiophys3.hoc" template_file = "models/L5PCtemplate.hoc" theseCoeffsAll = theseCoeffsAllAll[icell] for idist in range(0,len(proximalpoints)): counter = counter + 1 proximalpoint = proximalpoints[idist] distalpoint = distalpoints[idist] fixedpoint = 700 idist_proximal = dists.index(proximalpoint) idist_distal = dists.index(distalpoint) Is_syn1 = IsAllAll_syn1[icell][idist_distal] if type(Is_syn1) is list: Is_syn1 = Is_syn1[-1] Is_st1 = IsAllAll_st1[icell][idist_proximal] if type(Is_st1) is list: Is_st1 = Is_st1[-1] h(""" load_file("stdlib.hoc") load_file("stdrun.hoc") objref cvode cvode = new CVode() cvode.active(1) cvode.atol(0.00001) load_file("import3d.hoc") objref L5PC load_file(\""""+biophys_file+"""\") load_file(\""""+template_file+"""\") L5PC = new L5PCtemplate(\""""+morphology_file+"""\") access L5PC.soma objref st1, st2 st2 = new IClamp(0.5) L5PC.soma st2 st2.amp = """+str(st2coeff*Is_st2)+""" st2.del = 1000 st2.dur = 5 objref vsoma, casoma, sksoma, vdend, vdend2, vdend3, cadend3, skdend3, tvec, isyn vsoma = new Vector() casoma = new Vector() sksoma = new Vector() vdend = new Vector() vdend2 = new Vector() vdend3 = new Vector() cadend3 = new Vector() skdend3 = new Vector() objref sl,ns,syn1,con1 isyn = new Vector() tvec = new Vector() sl = new List() double siteVec[2] sl = L5PC.locateSites("apic","""+str(distalpoint)+""") maxdiam = 0 for(i=0;i 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 L5PC.apic[siteVec[0]] cvode.record(&v(siteVec[1]),vdend,tvec) L5PC.apic[siteVec[0]] { syn1 = new epsp(siteVec[1]) syn1.tau0 = 0.5 syn1.tau1 = 5 syn1.onset = 1000 + """+str(BACdt)+""" syn1.imax = """+str(syn1coeff*Is_syn1)+""" cvode.record(&syn1.i,isyn,tvec) } sl = L5PC.locateSites("apic","""+str(proximalpoint)+""") maxdiam = 0 for(i=0;i maxdiam) { j = i maxdiam = dd } } siteVec[0] = sl.o[j].x[0] siteVec[1] = sl.o[j].x[1] print "proximalpoint gCa_HVA: ", L5PC.apic[siteVec[0]].gCa_HVAbar_Ca_HVA print "proximalpoint gCa_LVA: ", L5PC.apic[siteVec[0]].gCa_LVAstbar_Ca_LVAst L5PC.apic[siteVec[0]] cvode.record(&v(siteVec[1]),vdend2,tvec) L5PC.apic[siteVec[0]] st1 = new IClamp(siteVec[1]) st1.amp = """+str(st1coeff*Is_st1)+""" st1.del = 700 st1.dur = 600 sl = L5PC.locateSites("apic","""+str(fixedpoint)+""") maxdiam = 0 for(i=0;i maxdiam) { j = i maxdiam = dd } } siteVec[0] = sl.o[j].x[0] siteVec[1] = sl.o[j].x[1] L5PC.apic[siteVec[0]] cvode.record(&v(siteVec[1]),vdend3,tvec) L5PC.apic[siteVec[0]] cvode.record(&cai(siteVec[1]),cadend3,tvec) L5PC.apic[siteVec[0]] cvode.record(&ik_SK_E2(siteVec[1]),skdend3,tvec) L5PC.soma cvode.record(&v(0.5),vsoma,tvec) L5PC.soma cvode.record(&cai(0.5),casoma,tvec) L5PC.soma cvode.record(&ik_SK_E2(0.5),sksoma,tvec) """) paramdict = paramdicts[icell] setparams(paramdict) 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'] 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]] lw = 0.5 VsomaupAll = [] VsomadownAll = [] VdendupAll = [] VdenddownAll = [] mutcounter = -1 for igene in range(0,len(MT)): VsomaupThisGene = [] VsomadownThisGene = [] VdendupThisGene = [] VdenddownThisGene = [] for imut in range(0,len(MT[igene])): VsomaupThisMut = [] VsomadownThisMut = [] VdendupThisMut = [] VdenddownThisMut = [] 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]): mutcounter = mutcounter + 1 if len(sys.argv) > 1 and int(float(sys.argv[1])) != mutcounter: continue if exists('updown2response_cs'+str(icell)+'_dist'+str(proximalpoints[idist])+'_'+str(distalpoints[idist])+'_'+str(igene)+'_'+str(imut)+'_'+str(iallmutval)+'.sav'): print 'updown2response_cs'+str(icell)+'_dist'+str(proximalpoints[idist])+'_'+str(distalpoints[idist])+'_'+str(igene)+'_'+str(imut)+'_'+str(iallmutval)+'.sav exists' continue CasomaupThisMutVal = [] CasomadownThisMutVal = [] SKsomaupThisMutVal = [] SKsomadownThisMutVal = [] VdendupThisMutVal = [] VdenddownThisMutVal = [] Vdend2upThisMutVal = [] Vdend2downThisMutVal = [] Vdend3upThisMutVal = [] Vdend3downThisMutVal = [] Cadend3upThisMutVal = [] Cadend3downThisMutVal = [] SKdend3upThisMutVal = [] SKdend3downThisMutVal = [] spikesupThisMutVal = [] spikesdownThisMutVal = [] timecoursedataThisMutVal = [] iters = [0,2,5,6,8,-1] #iters = [-1] for iiter in range(0,len(iters)): iter = iters[iiter] CasomaupThisIter = [] CasomadownThisIter = [] SKsomaupThisIter = [] SKsomadownThisIter = [] VdendupThisIter = [] VdenddownThisIter = [] Vdend2upThisIter = [] Vdend2downThisIter = [] Vdend3upThisIter = [] Vdend3downThisIter = [] Cadend3upThisIter = [] Cadend3downThisIter = [] SKdend3upThisIter = [] SKdend3downThisIter = [] spikesupThisIter = [] spikesdownThisIter = [] timecoursedataThisIter = [] 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('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 idt in range(0,len(epspdts)): for iup in range(0,2): syn1coeff = 0.5 - 0.35*(icell > 1 or (icell > 0 and iup == 1)) #Synaptic epsp-like input print "st1.amp = "+str(st1coeff*Is_st1*(1-iup)) print "st2.amp = "+str((st2coeff*(1-iup) + st2coeff_down*iup)*Is_st2) print "syn1.imax = "+str(syn1coeff*Is_syn1) h("st1.amp = "+str(st1coeff*Is_st1*(1-iup))) h("st2.amp = "+str((st2coeff*(1-iup) + st2coeff_down*iup)*Is_st2)) h("syn1.imax = "+str(syn1coeff*Is_syn1)) h(""" tstop = """+str(tstop)+""" cai0_ca_ion = """+str(thisCa)+""" v_init = """+str(v0)+""" syn1.onset = """+str(1000+epspdts[idt])+""" """) h.init() try: h.run() except RuntimeError: print "Too large I!" continue times=np.array(h.tvec) Vsoma=np.array(h.vsoma) Casoma=np.array(h.casoma) SKsoma=np.array(h.sksoma) Vdend=np.array(h.vdend) Vdend2=np.array(h.vdend2) Vdend3=np.array(h.vdend3) Cadend3=np.array(h.cadend3) SKdend3=np.array(h.skdend3) spikes = mytools.spike_times(times,Vsoma,-35,-45) if iup == 1: CasomadownThisIter.append(max(Casoma)) SKsomadownThisIter.append(max(SKsoma)) VdenddownThisIter.append(max(Vdend)) Vdend2downThisIter.append(max(Vdend2)) Vdend3downThisIter.append(max(Vdend3)) Cadend3downThisIter.append(max(Cadend3)) SKdend3downThisIter.append(max(SKdend3)) spikesdownThisIter.append(spikes[:]) else: CasomaupThisIter.append(max(Casoma)) SKsomaupThisIter.append(max(SKsoma)) VdendupThisIter.append(max(Vdend)) Vdend2upThisIter.append(max(Vdend2)) Vdend3upThisIter.append(max(Vdend3)) Cadend3upThisIter.append(max(Cadend3)) SKdend3upThisIter.append(max(SKdend3)) spikesupThisIter.append(spikes[:]) if epspdts[idt] in epspdts_savetimecourses: times_tc = [680+x for x in range(0,641)] Vsoma_tc = mytools.interpolate(times,Vsoma,times_tc) Casoma_tc = mytools.interpolate(times,Casoma,times_tc) SKsoma_tc = mytools.interpolate(times,SKsoma,times_tc) Vdend_tc = mytools.interpolate(times,Vdend,times_tc) Vdend2_tc = mytools.interpolate(times,Vdend2,times_tc) Vdend3_tc = mytools.interpolate(times,Vdend3,times_tc) Cadend3_tc = mytools.interpolate(times,Cadend3,times_tc) SKdend3_tc = mytools.interpolate(times,SKdend3,times_tc) picklelist = [times_tc[:],Vsoma_tc[:],Casoma_tc[:],SKsoma_tc[:],Vdend_tc[:],Vdend2_tc[:],Vdend3_tc[:],Cadend3_tc[:],SKdend3_tc[:],epspdts_savetimecourses] timecoursedataThisIter.append(picklelist[:]) file = open('updown2responsetimecourse_cs'+str(icell)+'_dist'+str(proximalpoints[idist])+'_'+str(distalpoints[idist])+'_'+str(igene)+'_'+str(imut)+'_'+str(iallmutval)+'.sav', 'w') pickle.dump(picklelist,file) file.close() #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]])+""" }""") CasomaupThisMutVal.append(CasomaupThisIter) SKsomaupThisMutVal.append(SKsomaupThisIter) VdendupThisMutVal.append(VdendupThisIter) Vdend2upThisMutVal.append(Vdend2upThisIter) Vdend3upThisMutVal.append(Vdend3upThisIter) Cadend3upThisMutVal.append(Cadend3upThisIter) SKdend3upThisMutVal.append(SKdend3upThisIter) CasomadownThisMutVal.append(CasomadownThisIter) SKsomadownThisMutVal.append(SKsomadownThisIter) VdenddownThisMutVal.append(VdenddownThisIter) Vdend2downThisMutVal.append(Vdend2downThisIter) Vdend3downThisMutVal.append(Vdend3downThisIter) Cadend3downThisMutVal.append(Cadend3downThisIter) SKdend3downThisMutVal.append(SKdend3downThisIter) spikesupThisMutVal.append(spikesupThisIter) spikesdownThisMutVal.append(spikesdownThisIter) timecoursedataThisMutVal.append(timecoursedataThisIter[:]) picklelist = [theseCoeffsAllAll,timecoursedataThisMutVal,epspdts_savetimecourses,MT] file = open('updown2responsetimecourse_cs'+str(icell)+'_dist'+str(proximalpoints[idist])+'_'+str(distalpoints[idist])+'_'+str(igene)+'_'+str(imut)+'_'+str(iallmutval)+'.sav', 'w') pickle.dump(picklelist,file) file.close() picklelist = [theseCoeffsAllAll,CasomaupThisMutVal,SKsomaupThisMutVal,VdendupThisMutVal,Vdend2upThisMutVal,Vdend3upThisMutVal,Cadend3upThisMutVal,SKdend3upThisMutVal, CasomadownThisMutVal,SKsomadownThisMutVal,VdenddownThisMutVal,Vdend2downThisMutVal,Vdend3downThisMutVal,Cadend3downThisMutVal,SKdend3downThisMutVal, spikesupThisMutVal,spikesdownThisMutVal,epspdts,MT] file = open('updown2response_cs'+str(icell)+'_dist'+str(proximalpoints[idist])+'_'+str(distalpoints[idist])+'_'+str(igene)+'_'+str(imut)+'_'+str(iallmutval)+'.sav', 'w') pickle.dump(picklelist,file) file.close()