// Detailed model of Cerebellar Granular Cell model
// New Parameters file - to set and distribute ion channels
// Last updated 07-Jan-2009
// Model developer: Shyam Diwakar M.
// Developed at Egidio D'Angelo's Lab at Univ of Pavia
// Code contributors: Thierry Nieus, Sergio Solinas
// Dept. of Gen. Physiology (Univ. of Pavia, Italy)
// School of biotech (Amrita University, India)
// Email:shyam@unipv.it
/* Model published as [Diwakar et al, J.Neurophysiology]
Shyam Diwakar, Jacopo Magistretti, Mitchell Goldfarb, Giovanni Naldi, and Egidio D'Angelo.
Axonal Na+ channels ensure fast spike activation and back-propagation in cerebellar granule cells, J Neurophysiol (December 10, 2008).
doi:10.1152/jn.90382.2008
*/
//A Panel for Channels and someof their controls
objref panel
panel = new VBox()
//new stuff 10 May 2005
Nag = Granule[0].soma.gnabar_GRC_NA
Kvg = Granule[0].soma.gkbar_GRC_KV
Kmg = Granule[0].soma.gkbar_GRC_KM
glL = 5.68e-5
ell = -16.5
ndend = 4
nsg = 5
naxon = 30
ncomp = 1+(4*ndend)+nsg+naxon
Rappaxon = ((9.76*9.76)/(naxon*Granule[0].axon[0].L*Granule[0].axon[0].diam))
Granule[0].soma.gnabar_GRC_NA = 0
Granule[0].soma.gkbar_GRC_KV = 0
KirGmax=0.0009 //Standard reference value - Kir
KaGmax=0.0032 //Standard reference value -Ka
CaGmax=0.00046 //Standard reference value - Ca
KCaGmax=0.003 //Standard reference value - KCa
beta=0.6 //Standard reference value - removal rate
inicon=0.001 //Standard reference value - Initial condition
//Configuration mode flags for state/compartment selection for ion channel distribution
Camode1 =0
Camode2 =0
Camode3 =0
Camode4 =1
CamodeS =0
KCamode1 =0
KCamode2 =0
KCamode3 =0
KCamode4 =1
KCamodeS=0
Kirmode1 =1
Kirmode2 =1
Kirmode3 =0
Kirmode4 =0
KirmodeS =0
Kamode1 =0
Kamode2 =0
Kamode3 =0
Kamode4 =0
KamodeS =1
//Compartment area estimation
SomaArea=Granule[0].soma.L*Granule[0].soma.diam*PI
Dend12Area=Granule[0].dend_1[0].L*Granule[0].dend_1[0].diam*PI
Dend34Area=Granule[0].dend_4[0].L*Granule[0].dend_4[0].diam*PI
SomascArea=PI*9.76*9.76
//Scale factors for compartaments
RappSomaDend12=SomascArea/(4*Dend12Area)
RappSomaDend34=SomascArea/(4*Dend34Area)
RappSomaNew=SomascArea/SomaArea
RappSomahill=SomascArea/(3.75*PI)
RappAH = 3.75/(naxon*Granule[0].axon[0].L*Granule[0].axon[0].diam)
gG = Granule[0].soma.ggaba_GRC_LKG2
// Functions to identify multiplecompartments - ignore description
proc alpKCaM() {
alpKCa = ($1==1)+($2==1)+($3==1)+($4==1)+($5==1)
}
proc alpCaM() {
alpCa = ($1==1)+($2==1)+($3==1)+($4==1)+($5==1)
}
proc alpKaM() {
alpKa = ($1==1)+($2==1)+($3==1)+($4==1)+($5==1)
}
proc alpKirM() {
alpKir = ($1==1)+($2==1)+($3==1)+($4==1)+($5==1)
}
gamma = 0.5 //Percentage of NA/Kv in axon-hillock
//For specific dendrite, axon and Hillock manipulations
NagH = Nag
KvgH = Kvg
NagA = Nag
KvgA = Kvg
KCaD = KCaGmax
CaD = CaGmax
DendFact=1 //default morphology scaling ratio
KaRapp = KaGmax
KirRapp = KirGmax
CaRapp = CaGmax
KCaRapp = KCaGmax
//For Dendritic Morphology Scaling - Unused
proc DendGeomFact(){
for (i=0;i<4;i=i+1) {
Granule[0].dend_1[i].diam=0.75/DendFact
Granule[0].dend_2[i].diam=0.75/DendFact
Granule[0].dend_3[i].diam=0.75/DendFact
Granule[0].dend_4[i].diam=0.75/DendFact
Granule[0].dend_1[i].L=5*DendFact
Granule[0].dend_2[i].L=5*DendFact
Granule[0].dend_3[i].L=2.5*DendFact
Granule[0].dend_4[i].L=2.5*DendFact
}
//print "L1= ",Granule[0].dend_1[0].L," L2= ",Granule[0].dend_2[0].L," L3= ",Granule[0].dend_3[0].L," L4= ",Granule[0].dend_4[0].L
//print "D1=D2=D3=D4= ",Granule[0].dend_1[0].diam
}
//Updating leakage current
proc glUpdate() {
Granule[0].soma.gl_GRC_LKG1 = glL*(RappSomaNew)*(2/3)
Granule[0].soma.el_GRC_LKG1 = ell
for(i=0;i<5;i=i+1) {
Granule[0].hillock[i].gl_GRC_LKG1=glL*(RappSomahill)*(1/15)
Granule[0].hillock[i].el_GRC_LKG1=ell
}
for(i=0;i<naxon;i=i+1) {
Granule[0].axon[i].gl_GRC_LKG1=glL*(Rappaxon)*(1/30)
Granule[0].axon[i].el_GRC_LKG1 =ell
}
for(i=0;i<4;i=i+1) {
Granule[0].dend_1[i].gl_GRC_LKG1=glL*(RappSomaDend12)*(1/16)
Granule[0].dend_2[i].gl_GRC_LKG1=glL*(RappSomaDend12)*(1/16)
Granule[0].dend_3[i].gl_GRC_LKG1=glL*(RappSomaDend34)*(1/16)
Granule[0].dend_4[i].gl_GRC_LKG1=glL*(RappSomaDend34)*(1/16)
Granule[0].dend_1[i].el_GRC_LKG1=ell
Granule[0].dend_2[i].el_GRC_LKG1=ell
Granule[0].dend_3[i].el_GRC_LKG1=ell
Granule[0].dend_4[i].el_GRC_LKG1=ell
}
}
proc gGUpdate() {
Granule[0].soma.ggaba_GRC_LKG2 = 0
for(i=0;i<4;i=i+1) {
Granule[0].dend_1[i].ggaba_GRC_LKG2=gG*(1/ndend)*(RappSomaDend12)
Granule[0].dend_2[i].ggaba_GRC_LKG2=gG*(1/ndend)*(RappSomaDend12)
Granule[0].dend_3[i].ggaba_GRC_LKG2=gG*(1/ndend)*(RappSomaDend34)
Granule[0].dend_4[i].ggaba_GRC_LKG2=gG*(1/ndend)*(RappSomaDend34)
}
}
//Updating Calcium buffer removal rate
proc UpdateBeta() {
//print "Updating Removal Rate of Calcium ----"
for (i=0;i<4;i=i+1) {
Granule[0].dend_1[i].beta_GRC_CALC = beta
//print "dend_1 [",i,"]beta =",Granule[0].dend_1[i].beta_GRC_CALC," |"
Granule[0].dend_2[i].beta_GRC_CALC = beta
//print "dend_2 [",i,"]beta =",Granule[0].dend_2[i].beta_GRC_CALC," |"
Granule[0].dend_3[i].beta_GRC_CALC = beta
//print "dend_3 [",i,"]beta =",Granule[0].dend_3[i].beta_GRC_CALC," |"
Granule[0].dend_4[i].beta_GRC_CALC = beta
//print "dend_4 [",i,"]beta =",Granule[0].dend_4[i].beta_GRC_CALC," |"
}
//print "Update Complete ---------------------"
}
//Updating Calcium shell thickness
proc UpdateShelld() {
//print "Updating Calcium Shell Thickness----"
/*for (i=0;i<4;i=i+1) {
Granule[0].dend_1[i].d_GRC_CALC = shell*RappSomaDend12
print "dend_1 [",i,"]d =",Granule[0].dend_1[i].d_GRC_CALC," |"
Granule[0].dend_2[i].d_GRC_CALC = shell*RappSomaDend12
print "dend_2 [",i,"]d =",Granule[0].dend_2[i].d_GRC_CALC," |"
Granule[0].dend_3[i].d_GRC_CALC = shell*RappSomaDend34
print "dend_3 [",i,"]d =",Granule[0].dend_3[i].d_GRC_CALC," |"
Granule[0].dend_4[i].d_GRC_CALC = shell*RappSomaDend34
print "dend_4 [",i,"]d =",Granule[0].dend_4[i].d_GRC_CALC," |"
}*/
//print "Improbable Update Terminating ---------------------"
}
//Updating initial Concentration
proc UpdateInicon() {
//print "Updating Initial Ca ion Conc--------"
for (i=0;i<4;i=i+1) {
Granule[0].dend_1[i].cai0_GRC_CALC = inicon
//print "dend_1 [",i,"]cai0 =",Granule[0].dend_1[i].cai0_GRC_CALC," |"
Granule[0].dend_2[i].cai0_GRC_CALC = inicon
//print "dend_2 [",i,"]cai0 =",Granule[0].dend_2[i].cai0_GRC_CALC," |"
Granule[0].dend_3[i].cai0_GRC_CALC = inicon
//print "dend_3 [",i,"]cai0 =",Granule[0].dend_3[i].cai0_GRC_CALC," |"
Granule[0].dend_4[i].cai0_GRC_CALC = inicon
//print "dend_4 [",i,"]cai0 =",Granule[0].dend_4[i].cai0_GRC_CALC," |"
}
//print "Update Complete ---------------------"
}
//Reset functions: resets to old state when checkbox is unticked
proc resetgs() {
Granule[0].soma.gkbar_GRC_KA = 0//KaRapp
Granule[0].soma.gcabar_GRC_CA = 0
Granule[0].soma.gkbar_GRC_KIR = 0//KirRapp
Granule[0].soma.gkbar_GRC_KCA = 0
}
proc resetgd1() {
for(i=0;i<4;i=i+1) {
Granule[0].dend_1[i].gkbar_GRC_KA = 0
Granule[0].dend_1[i].gcabar_GRC_CA = 0
Granule[0].dend_1[i].gkbar_GRC_KIR = 0
Granule[0].dend_1[i].gkbar_GRC_KCA = 0
}
}
proc resetgd2() {
for(i=0;i<4;i=i+1) {
Granule[0].dend_2[i].gkbar_GRC_KA = 0
Granule[0].dend_2[i].gcabar_GRC_CA = 0
Granule[0].dend_2[i].gkbar_GRC_KIR = 0
Granule[0].dend_2[i].gkbar_GRC_KCA = 0
}
}
proc resetgd3() {
for(i=0;i<4;i=i+1) {
Granule[0].dend_3[i].gkbar_GRC_KA = 0
Granule[0].dend_3[i].gcabar_GRC_CA = 0
Granule[0].dend_3[i].gkbar_GRC_KIR = 0
Granule[0].dend_3[i].gkbar_GRC_KCA = 0
}
}
proc resetgd4() {
for(i=0;i<4;i=i+1) {
Granule[0].dend_4[i].gkbar_GRC_KA = 0
Granule[0].dend_4[i].gcabar_GRC_CA = 0
Granule[0].dend_4[i].gkbar_GRC_KIR = 0
Granule[0].dend_4[i].gkbar_GRC_KCA = 0
}
}
proc resetg() {
if($1==0) {
resetgs()
}
if($2==0) {
resetgd1()
}
if($3==0) {
resetgd2()
}
if($4==0) {
resetgd3()
}
if($5==0) {
resetgd4()
}
}
proc KaU(){
//print "Refresh Ka"
alpKaM($1,$2,$3,$4,$5)
if(alpKa>=1) {
for (i=0;i<4;i=i+1) {
Granule[0].soma.gkbar_GRC_KA=KaGmax*(1/alpKa)*RappSomaNew*$1
Granule[0].dend_1[i].gkbar_GRC_KA=KaGmax*RappSomaDend12*(1/alpKa)*$2
Granule[0].dend_2[i].gkbar_GRC_KA=KaGmax*RappSomaDend12*(1/alpKa)*$3
Granule[0].dend_3[i].gkbar_GRC_KA=KaGmax*RappSomaDend34*(1/alpKa)*$4
Granule[0].dend_4[i].gkbar_GRC_KA=KaGmax*RappSomaDend34*(1/alpKa)*$5
}
}
}
proc CaU(){
//print "Refresh Ca"
alpCaM($1,$2,$3,$4,$5)
if(alpCa>=1) {
for (i=0;i<4;i=i+1) {
Granule[0].soma.gcabar_GRC_CA=CaGmax*(1/alpKa)*RappSomaNew*$1
Granule[0].dend_1[i].gcabar_GRC_CA=CaD*RappSomaDend12*(1/alpCa)*$2
Granule[0].dend_2[i].gcabar_GRC_CA=CaD*RappSomaDend12*(1/alpCa)*$3
Granule[0].dend_3[i].gcabar_GRC_CA=CaD*RappSomaDend34*(1/alpCa)*$4
Granule[0].dend_4[i].gcabar_GRC_CA=CaD*RappSomaDend34*(1/alpCa)*$5
}
}
}
proc KCaU(){
//print "Refresh KCa"
//if($1==1) ->addstuff to modify shell d in soma
alpKCaM($1,$2,$3,$4,$5)
if(alpKCa>=1) {
for (i=0;i<4;i=i+1) {
Granule[0].soma.gkbar_GRC_KCA=KCaD*(1/alpKCa)*RappSomaNew*$1
Granule[0].dend_1[i].gkbar_GRC_KCA=KCaD*RappSomaDend12*(1/alpKCa)*$2
Granule[0].dend_2[i].gkbar_GRC_KCA=KCaD*RappSomaDend12*(1/alpKCa)*$3
Granule[0].dend_3[i].gkbar_GRC_KCA=KCaD*RappSomaDend34*(1/alpKCa)*$4
Granule[0].dend_4[i].gkbar_GRC_KCA=KCaD*RappSomaDend34*(1/alpKCa)*$5
}
}
}
proc KirU(){
//print "Refresh Kir"
alpKirM($1,$2,$3,$4,$5)
if(alpKir>=1) {
for (i=0;i<4;i=i+1) {
Granule[0].soma.gkbar_GRC_KIR=KirGmax*(1/alpKir)*RappSomaNew*$1
Granule[0].dend_1[i].gkbar_GRC_KIR=KirGmax*RappSomaDend12*(1/alpKir)*$2
Granule[0].dend_2[i].gkbar_GRC_KIR=KirGmax*RappSomaDend12*(1/alpKir)*$3
Granule[0].dend_3[i].gkbar_GRC_KIR=KirGmax*RappSomaDend34*(1/alpKir)*$4
Granule[0].dend_4[i].gkbar_GRC_KIR=KirGmax*RappSomaDend34*(1/alpKir)*$5
}
}
}
//for Na in axon/hillock
proc NaAUpdate() {
//print "Updating Na in axon"
for(i=0;i<naxon;i=i+1) {
access Granule[0].axon[i]
Granule[0].axon[i].gnabar_GRC_NA = NagA*(1-gamma)*Rappaxon-0.00232//*(1/naxon)//axon n hillock
Granule[0].axon[i].gkbar_GRC_KV = KvgA*(1-gamma)*Rappaxon-0.00232//*(1/naxon)
}
}
proc NaHUpdate() {
//print "Updating Na in hillock"
for(i=0;i<5;i=i+1) {
access Granule[0].hillock[i]
Granule[0].hillock[i].gnabar_GRC_NA = NagH*gamma*RappSomahill-0.00243
Granule[0].hillock[i].gkbar_GRC_KV = KvgH*gamma*RappSomahill-0.00243
}
}
UpdateBeta()
UpdateInicon()
betad = 0.8
glUpdate()
//For axon and Hill
NagH = Nag
KvgH = Kvg
NagA = Nag
KvgA = Kvg
KcaB = KCaGmax
CaB = CaGmax
proc UpdateHA() {
//print "Updating Hillock-Axon Conductances"
glUpdate()
NaHUpdate()
NaAUpdate()
}
//Activate default set
resetg(0,0,0,0,0)
NaAUpdate()
NaHUpdate()
glUpdate()
gGUpdate()
KaU(1,0,0,0,0)
CaU(0,0,0,0,1)
KCaU(0,0,0,0,1)
KirU(1,0,0,0,0)
//Dendritic params
KcaDe = KCaGmax
CaDe = CaGmax
proc CaDup() {
//print "Updating Ca/KCa in dendrite(s)"
for(i=0;i<ndend;i=i+1) {
access Granule[0].dend_4[i]
Granule[0].dend_4[i].gcabar_GRC_CA = CaDe*RappSomaDend34
Granule[0].dend_4[i].gkbar_GRC_KCA = KcaDe*RappSomaDend34
}
}
CaDup()
glUpdate()
gGUpdate()
inicon=0.00225
UpdateInicon()
beta=0.6
UpdateBeta()
NagH=0.019 //for spike amplitude
NaAUpdate()
NaHUpdate()
// Setting low leak in passive compartments
Granule[0].branch0.gl_GRC_LKG1=0.000000005
Granule[0].branch1.gl_GRC_LKG1=0.000000005
Granule[0].branch2.gl_GRC_LKG1=0.000000005
Granule[0].branch3.gl_GRC_LKG1=0.000000005
//Ion channel properties gmax panel
panel.intercept(1)
xpanel("1")
xlabel("***Na/Kv parameters***")
xvalue("H/A ratio","gamma", 1,"UpdateHA()", 0, 0 )
xlabel("Parameters of hillock compartments")
xvalue("gNabar","NagH", 1,"NaHUpdate()", 0, 0 )
xvalue("gKvbar","KvgH", 1,"NaHUpdate()", 0, 0 )
xlabel("Parameters of axon compartments")
xvalue("gNabar","NagA", 1,"NaAUpdate()", 0, 0 )
xvalue("gKvbar","KvgA", 1,"NaAUpdate()", 0, 0 )
xlabel("***Calcium params***")
xvalue("gCabar","CaDe", 1,"CaDup()", 0, 0 )
xvalue("gKCabar","KcaDe", 1,"CaDup()", 0, 0 )
xlabel("***Other K+ params***")
xvalue("Ka-gmax","KaGmax", 1,"KaU(1,0,0,0,0)", 0, 0 )
xvalue("Kir-gmax","KirGmax", 1,"KirU(1,0,0,0,0)", 0, 0 )
xlabel("***Leakage params***")
xvalue("Lkg1","glL", 1,"glUpdate()", 0, 0 )
xvalue("Lkg2","gG", 1,"gGUpdate()", 0, 0)
xpanel()
panel.intercept(0)
panel.map("Channels-n-Controls")
UpdateHA()