// Single shock synaptic stimulation of increasing numbers of synapses
// distributed uniformly on a single apical oblique branch. This experiment is used to
// show how A+B type stimulation can be sublinear, linear or supralinear
// depending on the strength and location of stimuli A,B
// The variable "times" is used to selected among a set of blockade cases to test
// times: 0 = control , 1 = block_A, 2 = block_NMDA, 3 = block_A_NMDA, 4 = block_Na, 5 = block_Ca
times = 0
load_file("nrngui.hoc")
load_file("../../template/load_templates.hoc")
objref econ // initialize template parameters
show_errs=1
debug_lev=1
econ=new ExperimentControl(show_errs,debug_lev)
econ.self_define(econ)
econ.morphology_dir = "../../morphology/n123" // set location for morphology files
econ.add_lib_dir("Terrence","../../lib") // set location for library files
econ.generic_dir = "../../experiment/" // set location for cell-setup file
econ.data_dir = "data" // create directory to store data
sprint(econ.syscmd, "mkdir -p %s", econ.data_dir)
system(econ.syscmd)
actual_resolution=75 // maximum nseg number
desired_resolution=1
econ.xopen_geometry_dependent("cell") // load raw cell morphology
econ.xopen_geometry_dependent("cell-analysis") // load user-defined semantics on morphology
cell_analysis(econ)
printf("Opening cell setup\n") // load cell-setup to
econ.xopen_generic("cell-setup") // specify all mechanisms,
printf("Opened. Setting up cell\n") // membrane properties etc
maximum_segment_length=actual_resolution
cell_setup(econ)
// Set simulation parameters for the experiment
econ.defvar("Simulation Control", "tstop", "260", "Defines when the simulation stops.")
econ.defvar("Simulation Control", "dt", "0.1", "Timestep")
econ.defvar("Simulation Control", "steps_per_ms", "10", "How many points are plotted per ms")
setdt()
// open files with NMDA/AMPA ratios
econ.xopen_geometry_dependent("nmda-ampa-ratio")
// Open file with tuned AMPA conductance values for all sections
objref tune_epsp_list
tune_epsp_list=new List()
strdef tunings_file, select, temp, accstr
sprint(tunings_file, "%s", "tunings")
xopen("../tune-synapses/tunings.dat")
// Open library functions that will be needed
load_template("SynapseBand")
econ.xopen_library("Terrence","choose-secs") // used to randomly select sections from a list
econ.xopen_library("Terrence","salloc") // used to allocate synapses on sections
econ.xopen_library("Terrence","deduce-ratio") // used to extract NMDA/AMPA, GABA_A/AMPA and GABA_B/GABA_B ratios
econ.xopen_library("Terrence","basic-graphics") // used to plot graphics
econ.xopen_library("Terrence","spikecount") // used to count spikes
synapses = 100 // maximum number of AMPA/NMDA synapses
maxruns = 2 // max number of runs for each synapse group in section (averaging)
minsyn = 2 // minimum number of synapses in selected section
maxsyn = 50 // maximum number of synapses in selected section
syn_step = 4 // step for increasing synapses in selected section
Deadtime_GLU=dt
Deadtime_NMDA=dt
hertz=2 // frequency of stimulation for all synapses (single pulse)
synch=0 // synapses are stimulated randomly (NOT synchronously)
perio=0 // spike trains for each synapse are NOT periodic
dendritic_spike_threshold=-25
somatic_spike_threshold= 0
objref band[2], rpid, vsoma, somarecf, vtip[100], dendrecf
objref ampa[synapses], nmda[synapses], splot, sl
strdef syscmd
objref apical_tip, vrec, vf
objref dendrec, meanvrec, maxvrec, meandendrec, maxdendrec, spikes, soma_spikes
meanvrec = new Vector(maxruns) // used to store the mean somatic depolarization in each run
maxvrec = new Vector(maxruns) // used to store the max somatic depolarization in each run
meandendrec = new Vector(maxruns) // used to store the mean dendritic depolarization in each run
maxdendrec = new Vector(maxruns) // used to store the max dendritic depolarization in each run
spikes = new Vector(maxruns) // used to store number of dendritic spikes per run
soma_spikes = new Vector(maxruns) // used to store number of somatic spikes per run
// Sections that could be used to plot traces
//addgraph("soma.v(0.5)",-72,20)
//addgraph("apical_dendrite[57].v(0.5)",-72,20) // Trunk middle
//addgraph("apical_dendrite[72].v(0.5)",-72,20) // Trunk distal 81 83 95 103 104
//addgraph("apical_dendrite[58].v(0.5)",-72,20) // Trunk middle
//addgraph("apical_dendrite[46].v(0.5)",-72,20) // Trunk proximal
//addgraph("apical_dendrite[45].v(0.5)",-72,20) // Tip proximal
//addgraph("apical_dendrite[59].v(0.5)",-72,20) // Trunk middle
//addgraph("apical_dendrite[68].v(0.5)",-72,20) // Tip midle
//addgraph("apical_dendrite[73].v(0.5)",-72,20) // Tip distal
//addgraph("apical_dendrite[82].v(0.5)",-72,20) // Tip distal
//addgraph( "v(0.5)",-72,0)
//Proceedures for the different cases to be tested
proc Ca_block() { // Block all Ca++ channels
forall if(ismembrane("cat")) {
for (x) { gcatbar_cat(x) = 0 }trunkl
}
forall if(ismembrane("calH")) {
for (x) { gcalbar_calH(x) = 0 }
}
forall if(ismembrane("cal")) {
for (x) { gcalbar_cal(x) = 0 }
}
forall if(ismembrane("car")) {
for (x) { gcabar_car(x) = 0 }
}
forall if(ismembrane("somacar")) {
for (x) { gcabar_somacar(x) = 0 }
}
}
proc Na_block() { // Block all Na+ channels
forall if(ismembrane("hha2")) {
for (x) { gnabar_hha2(x) = 0 }
}
forall if(ismembrane("hha_old")) {
for (x) { gnabar_hha_old(x) = 0 }
}
}
proc NMDA_block() { // Block NMDA current
for i=0, synapses -1 {
nmda[i].gmax = 0
}
}
proc A_block() { // Block all A-type K+ channels
f = 0.2
forall if(ismembrane("kad")) { // distal conductances
for(x) { gkabar_kad(x)= gkabar_kad(x)*f }
} else if(ismembrane("kap")) { // proximal conductances
for(x) { gkabar_kap(x)= gkabar_kap(x)*f }
}
}
proc A_NMDA_block() { // block both A-current and NMDA current
NMDA_block()
A_block()
}
// Use to make a list with all apical obliques within 200 um from soma
//sl=new SectionList()
//apical_dendrite[111] sl.append() // 1 degree 106.30
//apical_dendrite[112] sl.append() // 0 degree 88.52
//apical_dendrite[114] sl.append() // 1 degree 123.9962
//apical_dendrite[115] sl.append() // 1 degree 117.79
//apical_dendrite[117] sl.append() // 1 degree 67.6363
//apical_dendrite[118] sl.append() // 1 degree 81.66
// Make a list of all apical tip sections to be used
objref splot, apical_tipl, sl
strdef csec, syscmd
apical_tipl=new SectionList()
sl=new SectionList()
forsec apical_tip_list {
apical_tipl.append()
sl.append()
}
forsec apical_tip_list_addendum {
sl.append()
}
if (times == 0 || times == 2) {
temporal_offset = 10
}else{
temporal_offset = 100 // leave some time for equalibrium to be reached when channels are blocked
}
tstop = tstop+temporal_offset // simulation time period
addgraph_2("soma.v(0.5)",0,tstop,-72,-20) // plot voltage at the soma
//prepare to record at soma
vsoma=new Vector((tstop-temporal_offset)/dt)
sprint(accstr, "vsoma.record(&soma.v(0.5))")
execute1(accstr)
//prepare to record at oblique sections
ind=0
forsec sl {
vtip[ind]=new Vector((tstop-temporal_offset)/dt)
sprint(accstr, "vtip[%d].record(&%s.v(0.5))", ind, secname())
execute1(accstr)
ind=ind+1
}
// Start the experiment
r = 0
forsec sl { // for all oblique dendrites in the list
nseg = maxsyn // number of segments in each section is set equal to max number of synapses
// to avoid inserting more than one synapses at the same location
// for increasing number for synapses in the branch
for (synapses=minsyn; synapses<=maxsyn; synapses=synapses+syn_step) {
for runs = 0, maxruns-1 { // for maxruns times
r = r + 1
rpid = new Random(5*r+1)
PID = rpid.discunif(0,1000)
if (synapses == minsyn) {
print secname(), "is where we assess potency."
strdef recordsec
sprint(recordsec, "%s.v(0.5)",secname())
addgraph(recordsec,-72,0) // plot voltage at currently accessed section
}
COLOR=4
splot=new Shape()
for si=1,synapses { // evenly devide synapses along apical oblique dendrite
posn = (2*si -1)/(2*synapses)
printf("ampa[%d] = new GLU(%g)\n", si-1, posn)
ampa[si-1] = new GLU(posn)
nmda[si-1] = new NMDA(posn)
salloc2(ampa[si-1],nmda[si-1],posn,1,splot,COLOR) // mark ampa synapses on graph
}
splot.flush()
splot.show(1)
GABA_flag = 0 // Don't make both AMPA/NMDA and GABA trains in shiftsyn_init
// create the stimulation trains for AMPA & NMDA synapses
econ.xopen_library("Terrence","shiftsyn-initA")
shiftsyn_init(synapses,tstop,dt,hertz,synch,perio,PID,temporal_offset, GABA_flag ,"ampa","nmda")
vrec=new Vector(tstop/dt) // prepare to record somatic voltage
vrec.record(&soma.v(0.5))
dendrec=new Vector(tstop/dt) // prepare to record dendritic voltage
dendrec.record(&v(0.5))
// Execute current-blockade proceedure specified
if (times == 0) {
sprint(select, "%s", "control")}
if (times == 1) {
A_block()
sprint(select, "%s", "block_A_80")}
if (times == 2) {
NMDA_block()
sprint(select, "%s", "block_NMDA")}
if (times == 3) {
A_NMDA_block()
sprint(select, "%s", "block_A_NMDA")}
if (times == 4) {
Na_block()
sprint(select, "%s", "block_Na")}
if (times == 5) {
Ca_block()
sprint(select, "%s", "block_Ca")}
print "secname = ", secname(), " case = ", select, " nseg = ", nseg, " synapses = ", synapses, " runs =", runs
finitialize(v_init) //Inbitialize and run the experiment
fcurrent()
run()
meanvrec.x(runs) = vrec.mean(temporal_offset/dt,tstop/dt -1) // mean somatic depolarization
maxvrec.x(runs) = vrec.max(temporal_offset/dt,tstop/dt -1) // max somatic depolarization
meandendrec.x(runs)= dendrec.mean(temporal_offset/dt,tstop/dt -1) // mean dendritic depolarization
maxdendrec.x(runs) = dendrec.max(temporal_offset/dt,tstop/dt -1) // max dendritic depolarization
spikes.x(runs) = spikecount(dendrec,dendritic_spike_threshold) // count current number of dendritic spikes
soma_spikes.x(runs) = spikecount(vrec, somatic_spike_threshold) // count current number of somatic spikes
}
// create the output file and write data in file
vf=new File()
sprint(temp, "data/%s/Apical_Tips/%s/", tunings_file, secname())
sprint(econ.syscmd, "mkdir -p %s", temp)
system(econ.syscmd)
sprint(econ.tmp_str2, "%s/%s_%d_%d", temp, select, minsyn, maxsyn)
vf.aopen(econ.tmp_str2)
vf.printf("%d %g %g %g %g %g %g %g %g %g %g %g %g\n", synapses, meanvrec.mean(), meanvrec.stdev(), maxvrec.mean(), maxvrec.stdev(), meandendrec.mean(), meandendrec.stdev(), maxdendrec.mean(), maxdendrec.stdev(), spikes.mean(), spikes.stdev(), soma_spikes.mean(), soma_spikes.stdev())
vf.close()
//Print somatic trace in the same directory
objref somarecf
somarecf=new File()
sprint(temp, "data/%s/Apical_Tips/%s/Vsoma_%d",tunings_file, secname(), synapses)
somarecf.wopen(temp)
vrec.printf(somarecf, "%g\n")
somarecf.close()
//Print dendritic trace in the same directory
objref dendrecf
dendrecf=new File()
sprint(temp, "data/%s/Apical_Tips/%s/Vlocal_%d",tunings_file, secname(),synapses)
dendrecf.wopen(temp)
dendrec.printf(dendrecf, "%g\n")
dendrecf.close()
//Use only to print graphics tp eps files
if (unix_mac_pc()==1) {
econ.xopen_library("Terrence","verbose-system")
for i=0,windex {
sprint(econ.tmp_str2, "data/%s/Apical_Tips/%s/graph-syns=%d-%d.eps", tunings_file, secname(), synapses, i)
win[i].printfile(econ.tmp_str2)
}
}
}
}