// In this model the application of aBeta is done by adjusting the max conductance of the
// transient A current in the dendrites and soma by the same values as measured by Chen.
objref basal_gkap_healthy,basal_gkad_healthy
objref soma_gkap_healthy // there is only proximal A current in soma
objref apic_gkap_healthy,apic_gkad_healthy
strdef tmp, tmp1
basal_gkap_healthy = new Vector()
basal_gkad_healthy = new Vector()
soma_gkap_healthy = new Vector()
apic_gkap_healthy = new Vector()
apic_gkad_healthy = new Vector()
pt3dconst(1) // sets 3dpts diameters as authoritative
// pt3dconst(0) // sets nseg diameters as authoritative
proc store_healthy_g_A() {
// the normal A current conductances are stored so they can be restored when running simulations
// that require several modifications of the healthy configuration
// forsec "basal" {if (ismembrane("kap")) {gkabar_kap *= (1-.465)}}
basal_gkap_healthy = new Vector()
basal_gkad_healthy = new Vector()
soma_gkap_healthy = new Vector()
apic_gkap_healthy = new Vector()
apic_gkad_healthy = new Vector()
// store proximal, distal A-type current values at each spatial location, x, in each section
i=0
forsec "basal" {
sprint(tmp,"%s",secname())
for (x) {
sprint(tmp1, \
"if (ismembrane(\"kap\")) { basal_gkap_healthy.append(%s.gkabar_kap(x)) }",tmp)
execute(tmp1)
sprint(tmp1, \
"if (ismembrane(\"kad\")) { basal_gkad_healthy.append(%s.gkabar_kad(x)) }",tmp)
execute(tmp1)
i += 1
}
}
// store apical dendrite values
i=0
forsec "apic" {
sprint(tmp,"%s",secname())
for (x) {
sprint(tmp1, \
"if (ismembrane(\"kap\")) { apic_gkap_healthy.append(%s.gkabar_kap(x)) }", tmp)
execute(tmp1)
sprint(tmp1, \
"if (ismembrane(\"kad\")) { apic_gkad_healthy.append(%s.gkabar_kad(x)) }", tmp)
execute(tmp1)
i += 1
}
}
// store the somatic value
soma_gkap_healthy.append(soma.gkabar_kap)
print "Healthy (initial conductances stored)"
}
proc restore_healthy_g_A() {
// the normal A current conductances are restored for simulations
// that require several modifications of the healthy configuration
// restore basal dendrite values
i=0
forsec "basal" {
sprint(tmp,"%s",secname())
for (x) {
sprint(tmp1, \
"if (ismembrane(\"kap\")) {%s.gkabar_kap(x)=basal_gkap_healthy.x[i]}",tmp)
execute(tmp1)
sprint(tmp1, \
"if (ismembrane(\"kad\")) {%s.gkabar_kad(x)=basal_gkad_healthy.x[i]}",tmp)
execute(tmp1)
i += 1
}
}
// restore apical dendrite values
i=0
forsec "apic" {
sprint(tmp,"%s",secname())
for (x) {
sprint(tmp1, \
"if (ismembrane(\"kap\")) {%s.gkabar_kap(x)=apic_gkap_healthy.x[i]}", tmp)
execute(tmp1)
sprint(tmp1, \
"if (ismembrane(\"kad\")) {%s.gkabar_kad(x)=apic_gkad_healthy.x[i]}",tmp)
execute(tmp1)
i += 1
}
}
// restore the somatic value
soma.gkabar_kap=soma_gkap_healthy.x[0]
}
proc apply_aBeta() {
// Chen C 2005 reports a 46.5% reduction of A in the dendrites and
// 31.5% reduction in the soma
if (alzheimers_flag==0) {
forsec "basal" {
if (ismembrane("kap")) {gkabar_kap *= (1-.465)}
if (ismembrane("kad")) {gkabar_kad *= (1-.465)}
}
forsec "apic" {
if (ismembrane("kap")) {gkabar_kap *= (1-.465)}
if (ismembrane("kad")) {gkabar_kad *= (1-.465)}
}
forsec "soma" {
if (ismembrane("kap")) {gkabar_kap *= (1-.315)}
// there is just kap in soma
}
print "A-beta applied"
}
alzheimers_flag=1
}
proc set_concentration() {
// Chen C 2005 reports a 46.5% reduction of A in the dendrites and
// 31.5% reduction in the soma for 100 uM acute aBeta application
// We further investigate how lesser concentrations of aBeta would
// effect the cell by modeling smaller concentrations with the
// assumption that the block would be linearly proportional to the
// the ratio of the smaller concentration to the full (100 uM).
restore_healthy_g_A() // start from healthy cell
forsec "basal" {
if (ismembrane("kap")) {gkabar_kap *= (1-aBeta_concentration_factor*.465)}
if (ismembrane("kad")) {gkabar_kad *= (1-aBeta_concentration_factor*.465)}
}
forsec "apic" {
if (ismembrane("kap")) {gkabar_kap *= (1-aBeta_concentration_factor*.465)}
if (ismembrane("kad")) {gkabar_kad *= (1-aBeta_concentration_factor*.465)}
}
forsec "soma" {
if (ismembrane("kap")) {gkabar_kap *= (1-aBeta_concentration_factor*.315)}
// there is just kap in soma
}
print "A-beta applied with concentration dependent factor of ",aBeta_concentration_factor
alzheimers_flag=1
}
proc remove_aBeta() {
// restore the max conductances by restoring the initial saved values
restore_healthy_g_A()
alzheimers_flag=0
print "Healthy (initial conductances restored)"
}
proc apply_basal_aBeta() {
forsec "basal" {
if (ismembrane("kap")) {gkabar_kap *= (1-.465)}
if (ismembrane("kad")) {gkabar_kad *= (1-.465)}
}
print "A-beta applied to basal dendrites"
alzheimers_flag=1
}
proc apply_apic_aBeta() {
forsec "apic" {
if (ismembrane("kap")) {gkabar_kap *= (1-.465)}
if (ismembrane("kad")) {gkabar_kad *= (1-.465)}
}
print "A-beta applied to apical dendrites"
alzheimers_flag=1
}
proc apply_soma_aBeta() {
forsec "soma" {
if (ismembrane("kap")) {gkabar_kap *= (1-.315)}
// there is just kap in soma
}
print "A-beta applied to soma"
alzheimers_flag=1
}
proc apply_proximal_aBeta() {
forall {
for (x) if (x>0 && x<1) { xdist = distance(x)
if (xdist > 100){
// distal
// if (ismembrane("kad")) {gkabar_kad(x) *= (1-.465)}
} else {
// proximal
if (ismembrane("kap")) {gkabar_kap(x) *= (1-.465)}
}
}
}
alzheimers_flag=1
print "A-beta applied to proximal dendrites"
}
proc apply_distal_aBeta() {
forall {
for (x) if (x>0 && x<1) { xdist = distance(x)
if (xdist > 100){
// distal
if (ismembrane("kad")) {gkabar_kad(x) *= (1-.465)}
} else {
// proximal
// if (ismembrane("kap")) {gkabar_kap(x) *= (1-.465)}
}
}
}
alzheimers_flag=1
print "A-beta applied to distal dendrites"
}
proc apply_primary_aBeta() {
forsec primary {
if (ismembrane("kap")) {gkabar_kap *= (1-.465)}
if (ismembrane("kad")) {gkabar_kad *= (1-.465)}
}
print "A-beta applied to primary dendrite"
alzheimers_flag=1
}
proc apply_obliques_aBeta() {
forsec obliques {
if (ismembrane("kap")) {gkabar_kap *= (1-.465)}
if (ismembrane("kad")) {gkabar_kad *= (1-.465)}
}
print "A-beta applied to oblique dendrites"
alzheimers_flag=1
}
proc apply_tuft_aBeta() {
forsec tuft {
if (ismembrane("kap")) {gkabar_kap *= (1-.465)}
if (ismembrane("kad")) {gkabar_kad *= (1-.465)}
}
print "A-beta applied to tuft dendrites"
alzheimers_flag=1
}
// the below functions added to allow the visualization of which dendrites were having
// aBeta applied to in the special cases of specific application. It was later determined
// that these functions left the diameters different than when they started due to
// the difference between the nseg version of the diameters and lengths and the pt3d version
// The functions were then rewritten to modify only the pt3d and renamed to appending the
// nseg suffix to retain them as an example of what can go wrong if you are using pt3d and
// adjust diameters during the simulation. Note: if you do want to experiment with these
// make sure to change the function call pt3dconst(1) to pt3dconst(0) near the top of this file.
proc inflate_distal_dend_nseg() {
forall {
for (x) {
if (x>0 && x<1) {
xdist = distance(x)
if (xdist > 100){
// distal
starting_value = diam(x)
diam(x) *= 10
print secname(),x," inflating from ",starting_value," to ", diam(x)
} else {
// proximal
}
}
}
}
}
proc deflate_distal_dend_nseg() {
forall {
for (x) {
if (x>0 && x<1) {
xdist = distance(x)
if (xdist > 100){
// distal
starting_value = diam(x)
diam(x) /= 10
print secname(),x," deflating from ",starting_value," to ", diam(x)
} else {
// proximal
}
}
}
}
}
proc inflate_proximal_dend_nseg() {
print "Inflate proximal processes"
forall {
print secname()
for (x) if (x>0 && x<1) { xdist = distance(x)
if (xdist > 100){
// distal
} else {
// proximal
print "Inflating ",secname(),", to diam(", x,")=",diam(x)*10,", old value=",diam(x)
diam(x) *= 10
}
}
}
}
proc deflate_proximal_dend_nseg() {
print "Deflate proximal processes"
forall {
for (x) {
if (x>0 && x<1) {
xdist = distance(x)
if (xdist > 100){
// distal
} else {
print "Deflating ",secname(),", to diam(", x,")=",diam(x)/10,", old value=",diam(x)
diam(x) /= 10
}
}
}
}
}
// these below functions added to make reversable inflation/deflation of process that
// are proximal or distal to the soma with 100 um as the cut-off
proc inflate_distal_dend() {
forall {
start_dist = distance(0)
for i=0, n3d()-1 {
xdist = start_dist + arc3d(i)
if (xdist > 100){
// distal
starting_value = diam3d(i)
pt3dchange(i, starting_value*10)
// print secname(),xdist," inflating from ",starting_value," to ", diam3d(i)
} else {
// proximal
}
}
}
}
proc deflate_distal_dend() {
forall {
start_dist = distance(0)
for i=0, n3d()-1 {
xdist = start_dist + arc3d(i)
if (xdist > 100){
// distal
starting_value = diam3d(i)
pt3dchange(i, starting_value/10)
// print secname(),xdist," deflating from ",starting_value," to ", diam3d(i)
} else {
// proximal
}
}
}
}
proc inflate_proximal_dend() {
forall {
start_dist = distance(0)
for i=0, n3d()-1 {
xdist = start_dist + arc3d(i)
if (xdist > 100){
// distal
} else {
// proximal
starting_value = diam3d(i)
pt3dchange(i, starting_value*10)
// print secname(),xdist," inflating from ",starting_value," to ", diam3d(i)
}
}
}
}
proc deflate_proximal_dend() {
forall {
start_dist = distance(0)
for i=0, n3d()-1 {
xdist = start_dist + arc3d(i)
if (xdist > 100){
// distal
} else {
// proximal
starting_value = diam3d(i)
pt3dchange(i, starting_value/10)
// print secname(),xdist," deflating from ",starting_value," to ", diam3d(i)
}
}
}
}
proc inflate_primary_dend() {
forsec primary {
for i=0, n3d()-1 {
starting_value = diam3d(i)
pt3dchange(i, starting_value*10)
}
}
}
proc deflate_primary_dend() {
forsec primary {
for i=0, n3d()-1 {
starting_value = diam3d(i)
pt3dchange(i, starting_value/10)
}
}
}
proc inflate_oblique_dend() {
forsec obliques {
for i=0, n3d()-1 {
starting_value = diam3d(i)
pt3dchange(i, starting_value*10)
}
}
}
proc deflate_oblique_dend() {
forsec obliques {
for i=0, n3d()-1 {
starting_value = diam3d(i)
pt3dchange(i, starting_value/10)
}
}
}
proc inflate_tuft_dend() {
forsec tuft {
for i=0, n3d()-1 {
starting_value = diam3d(i)
pt3dchange(i, starting_value*10)
}
}
}
proc deflate_tuft_dend() {
forsec tuft {
for i=0, n3d()-1 {
starting_value = diam3d(i)
pt3dchange(i, starting_value/10)
}
}
}
proc apic_resize() {
// apic_resize_factor=1 default value doesn't change anything, 10, 1/10 typical choices
// apic_comp_index selects in text box which compartment is specifically changed, 0-128 valid choices
apic[apic_comp_index] {
for i=0, n3d()-1 {
starting_value = diam3d(i)
pt3dchange(i, starting_value*apic_resize_factor)
}
}
}
proc inflate_chen_electrode() {
forall {
start_dist = distance(0)
for i=0, n3d()-1 {
xdist = start_dist + arc3d(i)
if ((xdist >= 240)&&(xdist <= 300)){
// inside Chen C 2005 electrode range fig 2
starting_value = diam3d(i)
pt3dchange(i, starting_value*10)
// print secname(),xdist," inflating from ",starting_value," to ", diam3d(i)
}
}
}
}
proc deflate_chen_electrode() {
forall {
start_dist = distance(0)
for i=0, n3d()-1 {
xdist = start_dist + arc3d(i)
if ((xdist >= 240)&&(xdist <= 300)){
// inside Chen C 2005 electrode range fig 2
starting_value = diam3d(i)
pt3dchange(i, starting_value/10)
// print secname(),xdist," deflating from ",starting_value," to ", diam3d(i)
}
}
}
}
Simulation Platform