Multicompartmental cerebellar granule cell model (Diwakar et al. 2009)

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Accession:116835
A detailed multicompartmental model was used to study neuronal electroresponsiveness of cerebellar granule cells in rats. Here we show that, in cerebellar granule cells, Na+ channels are enriched in the axon, especially in the hillock, but almost absent from soma and dendrites. Numerical simulations indicated that granule cells have a compact electrotonic structure allowing EPSPs to diffuse with little attenuation from dendrites to axon. The spike arose almost simultaneously along the whole axonal ascending branch and invaded the hillock, whose activation promoted spike back-propagation with marginal delay (<200 micros) and attenuation (<20 mV) into the somato-dendritic compartment. For details check the cited article.
Reference:
1 . Diwakar S, Magistretti J, Goldfarb M, Naldi G, D'Angelo E (2009) Axonal Na+ channels ensure fast spike activation and back-propagation in cerebellar granule cells. J Neurophysiol 101:519-32 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism: Cerebellum;
Cell Type(s): Cerebellum interneuron granule GLU cell;
Channel(s): I A; I M; I h; I K,Ca; I Sodium; I Calcium; I Potassium; I A, slow;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Action Potential Initiation; Active Dendrites; Detailed Neuronal Models; Axonal Action Potentials; Action Potentials; Intrinsic plasticity;
Implementer(s): Diwakar, Shyam [shyam at amrita.edu];
Search NeuronDB for information about:  Cerebellum interneuron granule GLU cell; I A; I M; I h; I K,Ca; I Sodium; I Calcium; I Potassium; I A, slow;
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GrC
fig10
readme.html
AmpaCOD.mod *
GRC_CA.mod *
GRC_CALC.mod *
GRC_GABA.mod *
GRC_KA.mod *
GRC_KCA.mod *
GRC_KIR.mod *
GRC_KM.mod *
GRC_KV.mod *
GRC_LKG1.mod *
GRC_LKG2.mod *
GRC_NA.mod *
NmdaS.mod *
Pregen.mod *
ComPanel.hoc
Grc_Cell.hoc
mosinit.hoc
Parametri.hoc
screenshot.jpg
simple.ses
Start.hoc
                            
// 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()


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