// Single shock synaptic stimulation of increasing number of synapses within trunk sections (stimulus A or B)
// This file is used in conjuction with file Trunk_AplusB.hoc where two trunk sections are stimulated simultaneously
// with A+B synapses. This experiment is used to show how A+B type stimualtion can be sublinear, linear or supralinear
// depending on the strength of stimuli A,B.
// times: 0 = control , 1 = block_A, 2 = block_NMDA, 3 = block_A_NMDA, 4 = block_Na, 5 = block_Ca
times = 0
system("mkdir data") // make directory for data produced
load_file("nrngui.hoc")
load_file("../../template/load_templates.hoc")
//load_proc("nrnmainmenu")
//load_template("ExperimentControl") // load needed templates
//load_template("EPSPTuning")
//load_template("RangeRef")
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)
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
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
strdef tunings_file, select, temp, accstr
objref tune_epsp_list
tune_epsp_list=new List()
sprint(tunings_file, "%s", "tunings")
xopen("../tune-synapses/tunings.dat")
// Open library functions that will be needed
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
init_val = 1
maxint = 4
all_synapses = 100
Deadtime_GLU=dt
Deadtime_NMDA=dt
objref trunkl, vsoma, vtrunk[10], dendrecf, sl, rpid
objref ampa[all_synapses], nmda[all_synapses], splot
objref somavrec, vf, trunkrec, somarecf
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
// Make a list of trunk sections to be used
trunkl=new SectionList()
forsec apical_trunk_list {
trunkl.append()
}
// keep only sections > 135 mu as per Cash and Yuste 99
apical_dendrite[0] trunkl.remove() // 14.30 microns
apical_dendrite[4] trunkl.remove() // 46.93
apical_dendrite[6] trunkl.remove() // 46.65
apical_dendrite[14]trunkl.remove() // 53.43
apical_dendrite[15]trunkl.remove() // 59.87
apical_dendrite[16]trunkl.remove() // 71.79
apical_dendrite[22]trunkl.remove() // 73.83
apical_dendrite[23]trunkl.remove() // 75.38
apical_dendrite[25]trunkl.remove() // 94.46
apical_dendrite[26]trunkl.remove() // 99.45
apical_dendrite[27]trunkl.remove() // 122.79
apical_dendrite[58]trunkl.remove() // too short
//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()
}
if (times == 0 || times == 2) {
temporal_offset = 10
}else {
temporal_offset = 120
}
tstop = 250 + temporal_offset
// Plot soma trace
addgraph_2("soma.v(0.5)",0,tstop,-72,-45)
r=0
forsec trunkl {
nseg = 1
// Define path step such that synapses are inserted
// in multiples of 2 microns from the center of the branch
distance() // set origin to 0
length = distance(1) // estimate branch length
if ((length/2 - int(length/2)) >= 0.5) {
nseg = int(length/2) + 1
} else {
nseg = int(length/2)
}
xstep = 1/nseg //step position corresponding to 2 um path steps
if ((nseg/2 - int(nseg/2)) >= 0.5) {
xcenter = int(nseg/2) + 1 // center position corresponding to the middle of branch
} else {
xcenter = int(nseg/2)
}
r = r+1
strdef recordsec
sprint(recordsec, "%s.v(0.5)",secname())
addgraph_2(recordsec,0,tstop,-72,-45) //Plot trace in stimulated section
synapses = 0
for intensity = 0, maxint-1 {
r = r + 1
rpid = new Random(5*r+1)
PID = int(rpid.uniform(0,1000))
synapses= synapses + init_val
if (nseg < synapses) {
nseg = synapses
xstep = 1/nseg
if ((nseg/2 - int(nseg/2)) >= 0.5) {
xcenter = int(nseg/2) + 1 // center position corresponding to the middle of branch
} else {
xcenter = int(nseg/2)
}
}
// Add AMPA, NMDA receptors at synaptic bands
COLOR=2
splot=new Shape()
for si=1,int(synapses/2) { // if synapses is even, distribute around center
posn = (xcenter - si)*xstep
ampa[2*si-2] = new GLU(posn)
nmda[2*si-2] = new NMDA(posn)
salloc2(ampa[2*si-2],nmda[2*si-2],posn,1,splot,COLOR)
posn = (xcenter + si)*xstep
ampa[2*si-1] = new GLU(posn)
nmda[2*si-1] = new NMDA(posn)
salloc2(ampa[2*si-1],nmda[2*si-1],posn,1,splot,COLOR)
}
if (synapses/2 - int(synapses/2) > 0 ) { // if synapses is odd, place a synapse in the middle
posn = xcenter*xstep
ampa[synapses-1] = new GLU(posn)
nmda[synapses-1] = new NMDA(posn)
salloc2(ampa[2*si-2],nmda[2*si-2],posn,1,splot,COLOR)
}
splot.flush()
splot.show(1)
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(), " synapses = ", synapses, "case = ", select
GABA_flag = 0 // Don't make both AMPA/NMDA and GABA trains in shiftsyn_initA
// 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,0)
somavrec=new Vector(tstop/dt)
somavrec.record(&soma.v(0.5)) // prepare to record at soma
trunkrec=new Vector(tstop/dt) // prepare to record at trunk section
sprint(accstr, "trunkrec.record(&%s.v(0.5))", secname())
execute1(accstr)
finitialize(v_init) // Initialize and run experiment
fcurrent()
run()
meanvrec = somavrec.mean(temporal_offset/dt,tstop/dt) // mean somatic depolarization
maxvrec = somavrec.max(temporal_offset/dt,tstop/dt) // max somatic depolarization
meandendrec = trunkrec.mean(temporal_offset/dt,tstop/dt) // mean trunk section depolarization
maxdendrec = trunkrec.max(temporal_offset/dt,tstop/dt) // max trunk section depolarization
spikes = spikecount(trunkrec,dendritic_spike_threshold) // trunk section spike number
soma_spikes = spikecount(somavrec,somatic_spike_threshold) // somatic spike number
// Create directory and file name to save data
sprint(econ.tmp_str, "data/%s/Trunk/%s/",tunings_file, secname())
sprint(econ.syscmd, "mkdir -p %s", econ.tmp_str)
system(econ.syscmd)
// Print data in file
vf=new File()
sprint(econ.tmp_str2, "%s/%s", econ.tmp_str, select)
vf.aopen(econ.tmp_str2)
vf.printf("%d %g %g %g %g %g %g\n", synapses, meanvrec, maxvrec, meandendrec, maxdendrec, spikes, soma_spikes)
vf.close()
//Print somatic trace
objref somarecf
somarecf=new File()
sprint(temp, "data/%s/Trunk/%s/Vsoma_%d",tunings_file, secname(),synapses)
somarecf.wopen(temp)
somavrec.printf(somarecf, "%g\n")
somarecf.close()
//Print trunk section trace
objref dendrecf
dendrecf=new File()
sprint(temp, "data/%s/Trunk/%s/Vlocal_%d",tunings_file, secname(),synapses)
dendrecf.wopen(temp)
trunkrec.printf(dendrecf, "%g\n")
dendrecf.close()
//Print eps files in specified directory
// econ.xopen_library("Terrence","verbose-system")
for i=0,windex {
sprint(econ.tmp_str, "data/%s/Trunk/%s",tunings_file, secname())
sprint(econ.tmp_str2, "%s/graph-syns=%d-%d.eps",econ.tmp_str, synapses, i)
win[i].printfile(econ.tmp_str2)
}
}
}