/* --------------------- PROCEEDURES USED IN CELL SETUP -------------------------*/
/* To make the distal membrane less conductive, vis-a-vis Stuart G.
and Spruston N., J. Neuroscience 18(10) 3501-3510, 1998, we deceay Rm
from proximal to distal sigmoidally
*/
proc Rm_sigmoid() { local rm
$o1.defvar("channel:pas","Rm_soma", "Rm_soma", "")
// $o1.defvar("channel:pas","Rm_end", "5e3", "")
$o1.defvar("channel:pas","Rm_end", "12e3", "")
$o1.defvar("channel:pas","dhalf", "200", "")
$o1.defvar("channel:pas","steep", "50", "")
for (x) {
xdist = find_vector_distance_precise(secname(),x) // calc. perpedicular distance
rm = Rm_soma + (Rm_end - Rm_soma)/(1.0 + exp((dhalf-xdist)/steep))
g_pas(x) = 1.0/rm
}
}
/* Changing Ra sigmoidally along the apical trunk (obsolete in this case)*/
proc Ra_sigmoid() {
$o1.defvar("channel:pas","Ra_soma", "Ra_soma", "")
// $o1.defvar("channel:pas","Ra_end", "Ra_default", "")
$o1.defvar("channel:pas","Ra_end", "35", "")
$o1.defvar("channel:pas","dhalf", "210", "")
$o1.defvar("channel:pas","steep", "50", "")
for (x) {
xdist = find_vector_distance_precise(secname(),x) //calc. perpedicular distance
Ra = Ra_soma + (Ra_end - Ra_soma)/(1.0 + exp((dhalf-xdist)/steep))
}
}
/* To make the distal trunk h-current conductance, g_h, about 7
times higher (at 300 um) than the somatic value vis-a-vis Magee
J., J. of Neuroscience 18(19) 7613-7624, 1998, we vary I_h
conductance sigmoidally along the apical trunk.
*/
proc apical_h_insert_sig() {
$o1.defvar("channel:h","gh_soma", "soma_hbar", "")
$o1.defvar("channel:h","gh_end", "soma_hbar*9", "")
$o1.defvar("channel:h","dhalf", "280", "")
$o1.defvar("channel:h","steep", "50", "")
for (x) {
xdist = find_vector_distance_precise(secname(),x) //calc. perpedicular distance
insert h
gbar_h(x) = gh_soma + (gh_end - gh_soma)/(1.0 + exp((dhalf-xdist)/steep))
}
}
/* Inserting A-type currents along the apical trunk in
a linearly increasing manner
*/
proc A_insert() {
$o1.defvar("channel:kap","kap_distal_maxfactor", "1", "maximum cond. factor in dendrites")
$o1.defvar("channel:kap","kap_distal_distance", "100", "distance in dendrites for maximum cond.")
$o1.defvar("channel:kad","kad_distal_distance", "500", "distance in dendrites for maximum cond.")
for (x) {
xdist=find_vector_distance_precise(secname(),x)
insert kap
insert kad
ek = -80
if (xdist < kap_distal_distance ) {
gkabar_kad(x) = 0
gkabar_kap(x) =soma_kap *(1+xdist/100)
} else if (xdist < kad_distal_distance ) {
gkabar_kap(x) = 0
gkabar_kad(x) = soma_kad*(1+xdist/100)
} else {
gkabar_kap(x) = 0
gkabar_kad(x) = soma_kad*6
}
}
}
/* Inserting K(Ca++)-type channels and calcium pumps along the
apical trunk with maximum conductances in 50 < xdist < 200
*/
proc apical_kca_insert() {
$o1.defvar("channel:kca","kca_distal_maxfactor", "1", "maximum cond. factor in dendrites")
// $o1.defvar("channel:kca","kca_distal_maxfactor", "0", "maximum cond. factor in dendrites")
$o1.defvar("channel:kca","kca_distal_distance", "200", "distance in dendrites for maximum cond.")
for (x) {
xdist = find_vector_distance_precise(secname(),x)
fr = xdist/kca_distal_distance
insert cad // calsium pump/buffering mechanism
insert kca // slow AHP K++ current
insert mykca // medium AHP K++ current
if (xdist < kca_distal_distance && xdist > 50) {
gbar_kca(x) = 5*soma_kca
gkbar_mykca = 2*mykca_init
} else {
gbar_kca(x) = 0.5*soma_kca
gkbar_mykca = 0.25*mykca_init
}
}
}
/* Inserting LVA Ca++ T-type channels along the apical trunk in
a linearly increasing manner, for xdist > 100 um
*/
proc apical_caT_insert() {
$o1.defvar("channel:cat","caT_distal_maxfactor", "4", "maximum cond. factor in dendrites")
$o1.defvar("channel:cat","caT_distal_distance", "350", "distance in dendrites for maximum cond.")
for (x) {
xdist = find_vector_distance_precise(secname(),x)
fr = xdist/caT_distal_distance
insert cat
if (xdist < 100) {
gcatbar_cat(x) = 0
} else {
gcatbar_cat(x) = caT_distal_maxfactor*soma_caT*fr
}
}
}
/* Inserting HVAm Ca++ R-type and HVA L-type channels along
the apical trunk. The R-type current is distributed in a fixed
conductance while the L-type current is distributed in a
maximum fixed conductance for distances xdist > 50 um and in a very
small conductance for xdist < 50 um
*/
proc apical_caR_caLH_insert() {
for (x) {
xdist = find_vector_distance_precise(secname(),x)
insert car
gcabar_car(x) = 0.1*soma_car
insert calH
if (xdist > 50) {
gcalbar_calH(x) = 2*soma_caLH //4.6*soma_caLH
} else {
gcalbar_calH(x) = 0.1*soma_caLH //0.1*soma_caLH
}
}
}
/* Setting conductances in all apical oblique dendrites so that the values of all dedrites after an initial section
are the same (or a multiple) as the values in apical_dendrite[46]. The values in the initial section of 50 um from
the parent trunk are set equal to the parent trunk conductances. For dendrites located beyond 300 (or/and 350) um,
we increase the Na+-persistent current, the A current, the Ca++ and K(Ca++) conductances and reduce the spike
attenuation coefficent. */
strdef khsection
proc khoblique_peri_decay() { local i,x,d
$o1.defvar("channel:obliques", "khsection", "\"apical_dendrite[46]\"", "Trunk section used for oblique conductance values")
$o1.defvar("morphology:apical-non-trunk", "peri_trunkl", "50.0", "Length of the peri-trunk region")
// Holding the conductance values from apical_dendrite[46]
//sprint($o1.tmp_str,"%s { hold_cat=gcatbar_cat(1) hold_car=soma_car hold_calH=soma_caLH hold_nap=0.0004*gnabar_hha_old }", khsection)
sprint($o1.tmp_str,"%s { hold_cat=gcatbar_cat(1) hold_car=soma_car hold_calH=soma_caLH hold_nap=0.0004*gna }", khsection)
execute1($o1.tmp_str)
//sprint($o1.tmp_str,"%s { hold_h=gbar_h(1) hold_ar2_hha_old=ar2_hha_old(1) hold_kdr=gkbar_hha_old(1) }", khsection)
sprint($o1.tmp_str,"%s { hold_h=gbar_h(1) hold_kdr=gkdr }", khsection)
execute1($o1.tmp_str)
sprint($o1.tmp_str,"%s { hold_g_pas=g_pas(1) hold_kap=gkabar_kap(1) hold_kad=gkabar_kad(1) }", khsection)
execute1($o1.tmp_str)
sprint($o1.tmp_str,"%s { hold_mykca=gkbar_mykca(1) hold_kca=gbar_kca(1) }", khsection)
execute1($o1.tmp_str)
for i=0,plcount {
// set the origin to the currently accessed section
access opl[i].trunk_section.sec
xdist = find_vector_distance_precise(secname(),0)
distance(0,1)
trunk_kap = gkabar_kap(1) // holding the parent trunk values
trunk_kad = gkabar_kad(1)
trunk_h = gbar_h(1)
trunk_pas = g_pas(1)
// trunk_Ra = Ra
trunk_car = gcabar_car(1)
trunk_calH = gcalbar_calH(1)
trunk_cat = gcatbar_cat(1)
trunk_kca = gbar_kca(1)
trunk_mykca = gkbar_mykca(1)
trunk_nap = 0.2*hold_nap // No persistent I_Na at the trunk => hold a small persent of hold_nap value
// trunk_ar2_hha_old = ar2_hha_old(1) // spike attenuation variable
sec_count=0
forsec pl[i] {
// printf("\t-- %s --\n", secname()) access all oblique paths from parent trunk to root oblique
if (!sec_count) { // skip all trunk sections
sec_count=sec_count+1
continue
}
insert kap
insert kad
insert h
insert pas
insert car
insert calH
insert cat
insert kca
insert mykca
insert nap
insert cad
e_pas = v_init
ek = -80
for (x) {
// diam(x)/2 // mine insertion
if (x > 0 && x < 1) {
d = distance(1,x)
if (d < peri_trunkl) { // for distances close to the parent trunk section keep trunk values
Ra = Ra_trunk
gkabar_kap(x) = trunk_kap
gkabar_kad(x) = trunk_kad
gbar_h(x) = trunk_h
g_pas(x) = trunk_pas
gcabar_car(x) = trunk_car
gcalbar_calH(x) = trunk_calH
gcatbar_cat(x) = trunk_cat
gbar_kca(x) = trunk_kca
gkbar_mykca = mykca_init
gnabar_nap(x) = trunk_nap
// ar2_hha_old(x) = trunk_ar2_hha_old
} else { // for further distances set conductances to apical_dendrite[46] values (or a multiple)
gkabar_kap(x) = hold_kap *(1+xdist/100)
gkabar_kad(x) = hold_kad *(1+xdist/100)
gbar_h(x) = hold_h
g_pas(x) = hold_g_pas
Ra = Ra_trunk
gcabar_car(x) =hold_car //trunk_car*5 // hold_car=soma_car
gcalbar_calH(x) = hold_calH
gcatbar_cat(x) = hold_cat
//ar2_hha_old(x) = 0.8*hold_ar2_hha_old // set to 80% of dend. 46 value
gbar_kca(x) =hold_kca
gkbar_mykca =1.1*mykca_init
gnabar_nap(x) = hold_nap
if (xdist > 300 ) { // for xdist > 300 um increase:
gcabar_car(x) = 13*hold_car //trunk_car*10 //13*hold_car // Ca++-R current,
gcalbar_calH(x) = 5*hold_calH //5*hold_calH //14*hold_calH // Ca++-L current,
gbar_kca(x) = 5*soma_kca // slow AHP current
// gkbar_hha_old(x) = 1.07*hold_kdr // delayed rectifier
//gkbar_hha_old(x) = 1.1*hold_kdr // delayed rectifier
}
if (xdist > 350) { // for xdist > 350 um increase even more:
gcalbar_calH(x)=6*hold_calH // 6*hold_calH //15*hold_calH // Ca++-L current,
//ar2_hha_old(x) = 0.95 // less spike attenuation
gnabar_nap(x)=2*hold_nap // Na+ persistent
}
if (xdist > 500) {
gkabar_kad(x) = hold_kad*6 // A-current,
}
}
}
}
sec_count=sec_count+1
}
}
}
/* Seting conductance values in all basal dendrites to be the
same as the values in apical_dendrite[14], except for the A
current conductance which is 0.6 times higher.
*/
proc khbasal_fixed() { local i,x,d
$o1.defvar("channel:basal", "khsection", "\"apical_dendrite[14]\"", "Trunk section used for basal conductance values")
sprint($o1.tmp_str,"%s { hold_g_pas=g_pas(1) hold_kap=gkabar_kap(1) hold_kad=gkabar_kad(1) hold_h=gbar_h(1)}", khsection)
execute1($o1.tmp_str)
forsec basal_tree_list {
insert kap
insert kad
insert h
insert pas
for (x) {
gkabar_kap(x) =1.6*hold_kap //1.6
gkabar_kad(x) = 1.6*hold_kad //1.6
gbar_h(x) = soma_hbar
g_pas(x) = hold_g_pas
Ra = Ra_basal
e_pas = v_init
ek = -80
}
}
}
/* The Na channels developed Mel and modified by Brannon,
Poirazi (hha2 and hha_old) both reduce activation as function
of voltage. In other words, they show actvity-dependent
attenuation of conductance. Within both of these mechanisms,
ar2 ([0..1]) is used to inversely describe the intensity of
voltage-dependent attenuation. 0 is maximum attenuation, 1 is
no attenuation.
Within the cell model, we vary the amount of attenuation along
the apical trunk as a function of distance from the cell body
such that proximal sections show little attenuation and distal
sections show comparably more (with the exception of distal
obliques).
We typically decay ar2 linearly from proximal to distal with
the maximum and minimum values of decay as
parameters. Initialize these parameters:
*/
/*_______ END OF PROCEEDURES ROUTINELY USED IN CELL SETUP______*/
//__________________________________________________________________________________________________________
/* ____________ CELL SET-UP PROCEEDURE _____________ */
maximum_segment_length=75
strdef sectype
objref CAN_temp, CAL_temp, CAT_temp, KAD_temp, KAP_temp, NA_temp
proc cell_setup() {
// Set passive membrane properties
$o1.defvar("passive", "Rm_trunk", "36900","Non-oblique dendritic specific membrane resistance.")
$o1.defvar("passive", "Rm_non_trunk", "36900","Apical oblique specific membrane resistance.")
$o1.defvar("passive", "Rm_basal", "46000","Basal specific membrane resistance.")
$o1.defvar("passive", "Rm_tip", "36900","Tip specific membrane resistance.")
$o1.defvar("passive", "Rm_soma", "20000", "Somatic specific membrane resistance.")
$o1.defvar("passive", "Rm_axon", "28000", "Axonal specific membrane resistance. ")
$o1.defvar("passive", "Ra_basal", "150","Basal specific axial resistance.")
$o1.defvar("passive", "Ra_trunk", "150","Somatic specific axial resistance.")
$o1.defvar("passive", "Ra_non_trunk","150","Somatic specific axial resistance.")
$o1.defvar("passive", "Ra_soma", "150","Somatic specific axial resistance.")
$o1.defvar("passive", "Ra_tip", "150","Apical tip specific axial resistance.")
$o1.defvar("passive", "Ra_axon", "50","Axonal specific axial resistance. ")
$o1.defvar("passive", "Cm_default", "1","Default specific capacitance.")
$o1.defvar("passive", "Cm_axon", "Cm_default","Axonal specific capacitance. ")
$o1.defvar("passive", "Cm_soma", "1","Somatic specific capacitance. ")
$o1.defvar("passive", "Cm_trunk", "1.192","Trunk specific capacitance.")
$o1.defvar("passive","Cm_non_trunk", "1.192","Oblique specific capacitance.")
$o1.defvar("passive", "Cm_basal", "1.144","Basal specific capacitance.")
$o1.defvar("passive", "Cm_tip", "1.192","Apical tip specific capacitance.")
// SEVERELY affects experiment results
$o1.defvar("general", "celsius", "34","Temperature of slice.")
// Set HH Sodium - Potassium properties
$o1.xopen_library("Terrence","cut-sections")
cut_sections(maximum_segment_length)
// make 3-d mapping of cell sections
$o1.xopen_library("Terrence","map-segments-to-3d")
map_segments_to_3d()
// Set initial conductance values
soma_caL =0.0005
soma_car =0.0003 // for dendrite
gsomacar =0.0001
soma_caLH =0.0003
soma_caT =0.00005
soma_km=0.001
potNa=50
mykca_init =0.045
soma_kca =0.003
soma_kap =0.0005
soma_hbar =1.8e-5
soma_kad = 0.0005
gna=0.035 //set to 0 to simulate TTX
gkdr=0.015
gnadend=0.0125 //set to 0 to simulate TTX
gkdrdend=0.009
gnanotrunk=0.035 //set to 0 to simulate TTX
gkdrnotrunk=0.015
AXKdr=1
AXNa=1
//v_init=-70
// Start inserting mechanisms in cell
sectype ="soma"
forsec "soma" {
insert na3
insert kdr
gbar_na3=gna
gkdrbar_kdr=gkdr
ena = potNa
insert pas // leak conductance
g_pas = 1/Rm_soma
e_pas = v_init
Ra = Ra_soma
cm= Cm_soma
insert h // h current
gbar_h = soma_hbar
K_h = 8.8
vhalf_h = -82
insert kap // proximal A current
gkabar_kap = soma_kap
ek = -80
insert km // m-type potassium current
gbar_km = soma_km
ek = -80
insert cal // HVA Ca++-L type current
gcalbar_cal = soma_caL
insert cat // LVA Ca++-T type current
gcatbar_cat = soma_caT
insert somacar // HVAm Ca++-R type current
gcabar_somacar = gsomacar
insert kca // K(Ca) sAHP potassium type current
gbar_kca = 5*soma_kca
insert mykca // K(Ca) mAHP potassium type current
gkbar_mykca = 5.5*mykca_init
insert cad // calcium pump/buffering mechanism
}
// Configure Axon
sectype="axon"
forsec axon_sec_list {
insert nax
insert kdr
gbar_nax=gna*AXNa
gkdrbar_kdr=gkdr*AXKdr
ena = potNa
insert pas // leak conductance
g_pas = 1/Rm_axon
e_pas = v_init
Ra = Ra_axon
cm = Cm_axon
insert km // m-type potassium current
gbar_km = 3*soma_km
ek = -80
insert kap // proximal A current
gkabar_kap = soma_kap
ek = -80
}
// Configure apical trunk
forsec apical_trunk_list {
apical_h_insert_sig($o1) // Inserting h-current
apical_caR_caLH_insert($o1) // Inserting Ca++ R-type and Ca++ L-type currents
apical_caT_insert($o1) // Inserting Ca++ T-type current
apical_kca_insert($o1) // Inserting K(Ca) sAHP and mAHP potassium currents
A_insert($o1) // Inserting A-current
insert na3
insert kdr
gbar_na3=gna
gkdrbar_kdr=gkdr
ena = potNa
insert pas // leak conductance
g_pas = 1/Rm_trunk
e_pas = v_init
Ra = Ra_trunk
cm = Cm_trunk
Rm_sigmoid($o1) // configure Rm along apical trunk
Ra_sigmoid($o1) // configure Ra along apical trunk
}
// Configure the apical-non-trunk section: insert basic mechanisms
sectype = "apical non-trunk"
forsec apical_non_trunk_list {
insert na3notrunk
insert kdr
gbar_na3notrunk=gnanotrunk
gkdrbar_kdr=gkdrnotrunk
ena = potNa
insert pas // passive properties
g_pas = 1/Rm_non_trunk
e_pas = v_init
Ra = Ra_non_trunk
cm = Cm_non_trunk
}
khoblique_peri_decay($o1) // Configure the apical oblique dendrites
// Configure the basal dendrites
sectype = "basal tree"
forsec basal_tree_list {
insert na3dend
insert kdr
gbar_na3dend=gnadend
gkdrbar_kdr=gkdrdend
ena = potNa
insert pas // passive properties
g_pas = 1/Rm_basal
e_pas = v_init
Ra = Ra_basal
cm = Cm_basal
Ra_sigmoid($o1) // configure Ra
}
khbasal_fixed($o1) // Configure basal dendrites
forsec "soma" { g_pas= 1/Rm_soma} // force Rm at all soma sections
forall if (ismembrane("kdr") ) {
ek = -77 //-77
}
forall if(ismembrane("ca_ion")) {
eca =140
ion_style("ca_ion",0,1,0,0,0)
vshift_ca = 0
}
econ.xopen_library("Terrence","current-balance")
current_balance(v_init)
}