CA1 pyramidal neuron: Ih current (Migliore et al. 2012)

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Accession:144541
NEURON files from the paper: Migliore M, Migliore R (2012) Know Your Current Ih: Interaction with a Shunting Current Explains the Puzzling Effects of Its Pharmacological or Pathological Modulations. PLoS ONE 7(5): e36867. doi:10.1371/journal.pone.0036867. Experimental findings on the effects of Ih current modulation, which is particularly involved in epilepsy, appear to be inconsistent. In the paper, using a realistic model we show how and why a shunting current, such as that carried by TASK-like channels, dependent on the Ih peak conductance is able to explain virtually all experimental findings on Ih up- or down-regulation by modulators or pathological conditions.
Reference:
1 . Migliore M, Migliore R (2012) Know your current I: interaction with a shunting current explains the puzzling effects of its pharmacological or pathological modulations PLoS One 7(5):e36867 [PubMed]
Citations  Citation Browser
Model Information (Click on a link to find other models with that property)
Model Type: Synapse; Channel/Receptor;
Brain Region(s)/Organism: Hippocampus;
Cell Type(s): Hippocampus CA1 pyramidal cell;
Channel(s): I Na,t; I A; I K; I M; I h; I Potassium;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Detailed Neuronal Models; Epilepsy; Synaptic Integration;
Implementer(s): Migliore, Michele [Michele.Migliore at Yale.edu];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal cell; I Na,t; I A; I K; I M; I h; I Potassium;
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Ih_current
readme.html
distr.mod *
h.mod *
kadist.mod
kaprox.mod
kdrca1.mod
km.mod
na3n.mod
naxn.mod
fig-5a.hoc
fig-5a.hoc'
fixnseg.hoc *
mosinit.hoc
ri06.hoc
screenshot.png
                            
load_file("nrngui.hoc")
cvode_active(1)

dist=1
rel=0.1

numaxon=1
numsoma=1
numbasal=74
numapical=42
numtrunk=37

xopen("ri06.hoc")             // geometry file
xopen("fixnseg.hoc")           

Rm = 20000
RmDend = Rm/1
RmSoma = Rm
RmAx = Rm

Cm    = 1.9
CmSoma= Cm
CmAx  = Cm
CmDend = Cm*1

RaAll= 80
RaSoma=80  
RaAx = 50

Vrest = -70 
dt = 0.1
gna =  .02
AXONM = 5
gkdr = 0.01
celsius = 35.0  
KMULT =  0.015 //to match exp.Fig.2b
gcan=0.0//005
gcal=0.0//005
gcat=0.0//005
ghd=0.6e-4// km=0.015
slope=14
half=265 
nash=0
pos=0.
qt=1
coeffRa=.7
gkm=0.01
pos=10


objref g, b,c, f,time, y, y2, y3,y4,y5,y6,time2, stim[3], distrx, distry, outfile, cdistry, syn[300]
objref distri, p, s, rsyn, nc[300], sref, blist[numtrunk], str1, str2, aplist, apc,  apc2, st[300]
strdef filename, dends, trunk

outfile = new File()
time = new Vector()
y = new Vector()
y2 = new Vector()
y3 = new Vector()
time2 = new Vector()
y4 = new Vector()
y5 = new Vector()
y6 = new Vector()

for i=0, numtrunk-1 {
blist[i] = new Vector()
}

aplist = new Vector(numapical)

forsec "axon" {insert pas e_pas=Vrest g_pas = 1/RmAx Ra=RaAx cm=CmAx}
forsec "soma" {insert pas e_pas=Vrest g_pas = 1/RmSoma Ra=RaSoma cm=CmSoma}
forsec "dend"{insert pas e_pas=Vrest g_pas = 1/RmDend Ra=RaAll cm=CmDend}
forsec "dend_5" {insert pas e_pas=Vrest g_pas = 1/RmDend Ra=RaAll cm=CmDend}
forsec "apic" {insert pas e_pas=Vrest g_pas = 1/RmDend Ra=RaAll cm=CmDend}

access soma

apc = new APCount(.5)
apc.thresh=-63

dend_5[10] {
apc2 = new APCount(.5)
apc2.thresh=-20
}

freq=100
geom_nseg()
tot=0
forall {tot=tot+nseg}
distance()

maxdist=0
forsec "dend_5" for(x) {if (distance(x)>maxdist) {maxdist=distance(x)}}
print "total # of segments (50Hz): ",tot, "  max path distance: ", maxdist

//*********mapping bifurcations******************


for i=0, numapical-1 apic[i] {
	while (!issection("dend_5.*")) {
//	print "before  ", i, secname()
	sref = new SectionRef()
	access sref.parent
	sprint(dends, secname())
	}
	print "apical ",i," ",dends
	for k=0, numtrunk-1 dend_5[k] {
	sprint(trunk,secname())
	x=strcmp(dends, trunk)
	if (x==0) {blist[k].append(i)  aplist.x[i]=k}
	}
}
//************************************************
 

tstim=1
strength = 1 /*namps*/
tstop=500

b = new VBox()
b.intercept(1)
g = new Graph()
g.size(0,tstop,-80,-40)
g.addvar("soma.v(0.5)",1,1,2*tstop,0,2)
g.xaxis(1)
c = new Graph()
c.size(0,20,-80,-60)
c.label(0.3,0.9,"peak somatic membrane potential")
c.xaxis(0)
c.color(1)
xpanel("") 
xbutton("run [ control ]", "loop()") 
xbutton("run [ ZD ] ", "zd()")
xpanel()
b.intercept(0) 
b.map() 
 

s = new NetStim(.5) 
s.start=300
s.interval=20
s.number=1

highindex=54321 // 12345
objref rc, rd
use_mcell_ran4()
rc = new Random()
rc.MCellRan4(highindex*2000)
rc.uniform(0,41)
rd = new Random()
rd.MCellRan4(highindex+4000)
rd.uniform(0,1)
low=100
high=500
weight=0

for i=0, 49 {

		flag=0
		while (flag==0) {
		comp=int(rc.repick()+0.5)
		tmp=rd.repick()
		apic[comp] {if (distance(tmp)<low || distance(tmp)>high) {flag=0} else{flag=1}}
		}
		apic[comp] {
		printf (" %d %g %d %g \n",i, distance(tmp),comp,tmp)
		syn[i] = new Exp2Syn(tmp)
		syn[i].e=0
		syn[i].tau1 = 0.5
		syn[i].tau2 = 20
		nc[i] = new NetCon(s,syn[i],0,0,weight*1.e-3)
		}
}

forall insert ds
forsec "axon" {   
                insert nax gbar_nax=gna*AXONM 
                insert kdr gkdrbar_kdr=gkdr*AXONM
                insert kap gkabar_kap = KMULT*AXONM
		insert km gbar_km=gkm
}

forsec "soma" {   
		insert hd ghdbar_hd=ghd	vhalfl_hd=-82
                insert na3 gbar_na3=gna
                insert kdr gkdrbar_kdr=gkdr
                insert kap gkabar_kap = KMULT
		insert km gbar_km=gkm
}

for i=0, numbasal-1 dend[i] {
		insert hd ghdbar_hd=ghd vhalfl_hd=-82 
                insert na3 gbar_na3=gna 
                insert kdr gkdrbar_kdr=gkdr
		insert kap gkabar_kap=0
		insert kad gkabar_kad=0

		for (x,0) { xdist = distance(x)
                	if (xdist>500) {xdist=500}
                		if (xdist > 100){
					vhalfl_hd=-90
                        		gkabar_kad(x) = KMULT*(1+xdist/100)
                			} else {
					vhalfl_hd=-82
                        		gkabar_kap(x) = KMULT*(1+xdist/100)
               				}
		}
}
                
forsec "dend_5" {
	insert ds
		insert hd ghdbar_hd=ghd
                insert na3 gbar_na3=gna 
                insert kdr gkdrbar_kdr=gkdr
		insert kap gkabar_kap=0
		insert kad gkabar_kad=0

		for (x,0) { xdist = distance(x)
                	ghdbar_hd(x) = ghd*(1+100/(1+exp((half-xdist)/slope)))
                	if (xdist>500) {xdist=500}
                		if (xdist > 100){
					vhalfl_hd=-90
                        		gkabar_kad(x) = KMULT*(1+xdist/100)
                			} else {
					vhalfl_hd=-82
                        		gkabar_kap(x) = KMULT*(1+xdist/100)
               				}
		}
}

for i=0, numapical-1 apic[i] {
	insert ds
	insert hd 
        insert na3 gbar_na3=gna 
        insert kdr gkdrbar_kdr=gkdr
	insert kap
	insert kad
	gkabar_kap=0
	gkabar_kad=0

		for (x,0) { xdist = distance(x)
                	ghdbar_hd(x) = ghd*(1+100/(1+exp((half-xdist)/slope)))
                		if (xdist > 100){
					vhalfl_hd=-90
                        		gkabar_kad(x) = KMULT*(1+xdist/100)
                			} else {
					vhalfl_hd=-82
                        		gkabar_kap(x) = KMULT*(1+xdist/100)
               				}
		}

	vhalfl_hd = dend_5[aplist.x[i]].vhalfl_hd
}


proc init() {
	t=0
	def()
	part=0
        forall {
        v=Vrest
	e_pas=Vrest
        if (ismembrane("nax") || ismembrane("na3")) {ena=55}
        if (ismembrane("kdr") || ismembrane("kap") || ismembrane("kad")) {ek=-90}
        if (ismembrane("hd") ) {ehd_hd=-30 elk_hd=-75 clk_hd=coeffRa}
	}
	finitialize(Vrest)
        fcurrent()

        forall {
	for (x) {
		}
	}
	cvode.re_init()
	cvode.event(20)
	cvode.event(290, "reset_peak()")
	cvode.event(5)
	cvode.event(tstop)
	access soma
	g.begin()

}

proc reset_peak() {
	forall for(x,0) {vmax_ds(x)=v}
}


proc advance() {
	fadvance()
	g.plot(t)
	g.flush()
	doNotify() 
}

proc loop() {
	for z=0, 49 {nc[z].weight=0e-3}
	ghd=6e-05
	apc.n=0
	flag=0
	while (flag<8) {
	run()	
	flag=flag+1
	if (apc.n<1 || apc.time<100) {
	vs =soma.vmax_ds(.5)
	print nc[0].weight*1e3*50, vs
	}
	for z=0, 49 {nc[z].weight=nc[z].weight+.05e-3}
	}
}

proc zd() {
	for z=0, 49 {nc[z].weight=0e-3}
	ghd=0
	apc.n=0
	flag=0
	while (flag<8) {
	run()	
	flag=flag+1
	if (apc.n<1 || apc.time<100) {
	print nc[0].weight*1e3*50, vs
	}
	for z=0, 49 {nc[z].weight=nc[z].weight+.05e-3}
	}
	}


proc def() {
forsec "soma" {ghdbar_hd=ghd*(1+100/(1+exp(half/slope)))  gbar_km=gkm}
forsec "axon" {gbar_km=gkm}

for i=0, numbasal-1 dend[i] {ghdbar_hd=ghd*(1+100/(1+exp(half/slope)))}
                
forsec "dend_5" {
		for (x,0) { xdist = distance(x)
                	ghdbar_hd(x) = ghd*(1+100/(1+exp((half-xdist)/slope)))
		}
}

for i=0, numapical-1 apic[i] {
	for (x,0) { xdist = distance(x)
                	ghdbar_hd(x) = ghd*(1+100/(1+exp((half-xdist)/slope)))
	}
}
} 


proc runp(){
stdinit()
continuerun(tstop)
distrx=new Vector()
distry=new Vector()
distrx.append(nc[0].weight*1e3*50)
distry.append(soma.vmax_ds(0.5))
if (ghd>0) {distry.mark(c,distrx,"O",7,2,2)} else {distry.mark(c,distrx,"O",7,3,2)}
c.flush()
doNotify()
}

proc run(){
runp(1)
}