Computational neuropharmacology of CA1 pyramidal neuron (Ferrante et al. 2008)

 Download zip file   Auto-launch 
Help downloading and running models
Accession:119283
In this paper, the model was used to show how neuroactive drugs targeting different neuronal mechanisms affect the signal integration in CA1 pyramidal neuron. Ferrante M, Blackwell KT, Migliore M, Ascoli GA (2008)
Reference:
1 . Ferrante M, Blackwell KT, Migliore M, Ascoli GA (2008) Computational models of neuronal biophysics and the characterization of potential neuropharmacological targets. Curr Med Chem 15:2456-71 [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: Hippocampus;
Cell Type(s): Hippocampus CA1 pyramidal GLU cell;
Channel(s): I Na,t; I A; I K; I h;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Action Potential Initiation; Action Potentials; Pathophysiology; Epilepsy; Synaptic Integration; Parkinson's; Aging/Alzheimer`s; Schizophrenia; Spike Frequency Adaptation;
Implementer(s): Ferrante, Michele [mferr133 at bu.edu];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; I Na,t; I A; I K; I h; Gaba; Glutamate;
/
FerranteEtAl2008
readme.html
distr.mod *
h.mod *
kadist.mod *
kaprox.mod *
kdrca1.mod *
na3n.mod *
naxn.mod *
netstimm.mod *
Fig.4E.hoc
fixnseg.hoc *
geo5038804.hoc *
mosinit.hoc
n128su.hoc *
n128su.ses *
screenshot.jpeg
                            
load_file("nrngui.hoc")
//cvode_active(1)
cvode.atol(0.001)

nsyn=5
weight=2 
low=50
high=400

nsyni=5
weighti=.2 
lowi=0
highi=5



highindex = 111

Rm = 28000
RmDend = Rm
RmSoma = Rm
RmAx = Rm

Cm    = 1
CmSoma= Cm
CmAx  = Cm
CmDend = Cm

RaAll= 150
RaSoma=150  
RaAx = 50

Vrest = -65
gna =  .03
AXONM = 2
gkdr = 0.001
celsius = 34.0  
KMULT =  0.01
KMULTP = 0.01
ghd=0.00006
nash=0
tstop=55
sh=0              

objref nc[nsyn], g, b, rsyn[nsyn], s[nsyn], rc, rd,re,nci[nsyni],rsyni[nsyni], si[nsyni],rf,rg,apc,outfile, nct,nil, tsp, savt


strdef filename

use_mcell_ran4()
lowindex = mcell_ran4_init()
rc = new Random()
rc.uniform(0,134)
rd = new Random()
rd.uniform(0,1)
re = new Random()
re.uniform(0,1)
rf = new Random()
rf.uniform(0,134)
rg = new Random()
rg.uniform(0,1)
xopen("n128su.hoc")             // geometry file

access soma
soma nct = new NetCon(&v(0.5), nil)
tsp = new Vector()
savt = new File()


savt.wopen("results/Valium.dat")

outfile = new File()
apc = new APCount(0.5)
apc.thresh=-20


for i=0, nsyn-1 {
	s[i] = new NetStimm(0.5)
	s[i].interval=10
	s[i].number = 100000000000
	s[i].start=re.repick()
	s[i].noise=1
	s[i].seed(highindex+3)
}
distance()

for i=0, nsyn-1 {
		rsyn[i] = new Exp2Syn(0.5)
		rsyn[i].e=0
		rsyn[i].tau1 = 5
		rsyn[i].tau2 = 10
		nc[i] = new NetCon(s[i],rsyn[i],0,0,weight*1.e-3)
}
for i=0, nsyni-1 {
	si[i] = new NetStimm(0.5)
	si[i].interval=10
	si[i].number = 10000000000
	si[i].start=re.repick()
	si[i].noise=0
	si[i].seed(highindex+3)
}
distance()

for i=0, nsyni-1 {
		rsyni[i] = new Exp2Syn(0.5)
		rsyni[i].e=-80
		rsyni[i].tau1 = 0.5
		rsyni[i].tau2 = 3
		nci[i] = new NetCon(si[i],rsyni[i],0,0,weighti*1.e-3)
}



	
b = new VBox()
b.intercept(1)
g = new Graph()
g.size(0,tstop,-70,20)
g.xaxis(1)
g.exec_menu("10% Zoom out")
g.addexpr("Fig. 4E (v_soma)","soma.v(0.5)",1,1, 0.2,0.9,2)
xpanel("",1)
xbutton("(1-4) Gray - Control", "runi()")
xbutton("(1) Black - Lamotrigine", "runii()")
xbutton("(2) Black - Diazepam", "runiii()")
xbutton("(3) Black - Flindokalner", "runiv()")
xbutton("(4) Black - Lamotrigine+Flindokalner", "runv()")
xpanel()
b.intercept(0)
b.map()

xopen("n128su.ses")
PlotShape[0].exec_menu("Shape Plot")
PlotShape[0].show(0)


proc init() {


axon[0] {   
                insert nax  gbar_nax=gna * AXONM
			sh_nax=nash
                insert kdr  gkdrbar_kdr=gkdr 
                insert pas e_pas=Vrest g_pas = 1/RmAx Ra=RaAx cm=CmAx
                insert kap gkabar_kap = KMULTP*0.2
}

soma {   
		insert hd ghdbar_hd=ghd
			vhalfl_hd==-82+sh
                insert na3  gbar_na3=gna     
			sh_na3=nash
			ar_na3=1
                insert kdr gkdrbar_kdr=gkdr
                insert kap gkabar_kap = KMULTP
                insert pas e_pas=Vrest g_pas = 1/RmSoma Ra=RaSoma cm=CmSoma
}

for i=135,ndend-1 dend[i] { //basal
                insert na3    gbar_na3=gna   
			sh_na3=nash
			ar_na3=1
                insert kdr gkdrbar_kdr=gkdr 
                insert kap gkabar_kap=KMULTP
                insert pas e_pas=Vrest g_pas = 1/RmDend Ra=RaAll cm=CmDend
}
                
for i=0,134 dend[i] { //apical
              insert pas e_pas=Vrest g_pas = 1/RmDend Ra=RaAll  cm=CmDend
		insert ds
		if (diam>0.5 && distance(0.5)<500) {
		insert hd ghdbar_hd=ghd
                insert na3 
		ar_na3=0.7
		gbar_na3=gna
                insert kdr 
		gkdrbar_kdr=gkdr
		insert kap
		insert kad
		gkabar_kap=0
		gkabar_kad=0

              for (x) if (x>0 && x<1) { xdist = distance(x)
                if (xdist>500) {xdist=500}
                ghdbar_hd(x) = ghd*(1+3*xdist/100)
                if (xdist > 100){
			vhalfl_hd==-90+sh
                        gkabar_kad(x) = KMULT*(1+xdist/100)
                } else {
			vhalfl_hd==-82+sh
                        gkabar_kap(x) = KMULTP*(1+xdist/100)
                	}
              				}
							}
				}

	t=0
        forall {
        v=Vrest
        if (ismembrane("nax") || ismembrane("na3")) {ena=55}
        if (ismembrane("kdr") || ismembrane("kap") || ismembrane("kad")) {ek=-90}
        if (ismembrane("hd") ) {ehd_hd=-30 }
	}
	finitialize(Vrest)
        fcurrent()

        forall {
	for (x) {
	if (ismembrane("na3")||ismembrane("nax")){e_pas(x)=v(x)+(ina(x)+ik(x))/g_pas(x)}
	if (ismembrane("hd")) {e_pas(x)=e_pas(x)+i_hd(x)/g_pas(x)}
		}
	}
	cvode.re_init()
	access soma
	g.begin()




}

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



proc reportloc() { local range 
  range = $o1.get_loc() 
  print "point process ", $o1, " is attached to ", secname(), " at ", range 
  pop_section() 
}	



proc runi() {
rc.MCellRan4(highindex+1)
	rd.MCellRan4(highindex+2)
	for i=0, nsyn-1 {
	s[i].seed(highindex+3)
	nc[i].weight = weight*1.e-3
	}
	for i=0, nsyn-1 {
		flag=0
		while (flag==0) {
		comp=int(rc.repick())
		tmp=rd.repick()
		dend[comp] {if (distance(tmp)<low || distance(tmp)>high) {flag=0} else{flag=1}}
		}
		dend[comp] {
			rsyn[i].loc(tmp)
			}
	}
	for i=0, nsyni-1 {
	si[i].seed(highindex+3)
	nci[i].weight = weighti*1.e-3
	}
	for i=0, nsyni-1 {
		flag=0
		while (flag==0) {
		compi=int(rf.repick())
		tmpi=rg.repick()
		dend[compi] {if (distance(tmpi)<low || distance(tmpi)>high) {flag=0} else{flag=1}}
		}
		dend[compi] {
			rsyni[i].loc(tmpi)
			}
	}

run()
}

proc runii() {
rc.MCellRan4(highindex+1)
	rd.MCellRan4(highindex+2)
	for i=0, nsyn-1 {
	s[i].seed(highindex+3)
	nc[i].weight = ((weight*1.e-3)/4)*3
        sh=10
	}
	for i=0, nsyn-1 {
		flag=0
		while (flag==0) {
		comp=int(rc.repick())
		tmp=rd.repick()
		dend[comp] {if (distance(tmp)<low || distance(tmp)>high) {flag=0} else{flag=1}}
		}
		dend[comp] {
			rsyn[i].loc(tmp)
			}
	}
	for i=0, nsyni-1 {
	si[i].seed(highindex+3)
	nci[i].weight = weighti*1.e-3
	}
	for i=0, nsyni-1 {
		flag=0
		while (flag==0) {
		compi=int(rf.repick())
		tmpi=rg.repick()
		dend[compi] {if (distance(tmpi)<low || distance(tmpi)>high) {flag=0} else{flag=1}}
		}
		dend[compi] {
			rsyni[i].loc(tmpi)
			}
	}
run()
}

proc runiii() {

rc.MCellRan4(highindex+1)
	rd.MCellRan4(highindex+2)
	for i=0, nsyn-1 {
	s[i].seed(highindex+3)
	nc[i].weight = weight*1.e-3
	}
	for i=0, nsyn-1 {
		flag=0
		while (flag==0) {
		comp=int(rc.repick())
		tmp=rd.repick()
		dend[comp] {if (distance(tmp)<low || distance(tmp)>high) {flag=0} else{flag=1}}
		}
		dend[comp] {
			rsyn[i].loc(tmp)
			}
	}
	
	for i=0, nsyni-1 {
	si[i].seed(highindex+3)
	nci[i].weight = (weighti*1.e-3)*50
	}
	for i=0, nsyni-1 {
		flag=0
		while (flag==0) {
		compi=int(rf.repick())
		tmpi=rg.repick()
		dend[compi] {if (distance(tmpi)<low || distance(tmpi)>high) {flag=0} else{flag=1}}
		}
		dend[compi] {
			rsyni[i].loc(tmpi)
			}
	}

run()
}

proc runiv() {
gkdr = 0.002
rc.MCellRan4(highindex+1)
	rd.MCellRan4(highindex+2)
	for i=0, nsyn-1 {
	s[i].seed(highindex+3)
	nc[i].weight = (weight*1.e-3)
	}
	for i=0, nsyn-1 {
		flag=0
		while (flag==0) {
		comp=int(rc.repick())
		tmp=rd.repick()
		dend[comp] {if (distance(tmp)<low || distance(tmp)>high) {flag=0} else{flag=1}}
		}
		dend[comp] {
			rsyn[i].loc(tmp)
			}
	}
	
	for i=0, nsyni-1 {
	si[i].seed(highindex+3)
	nci[i].weight = weighti*1.e-3
	}
	for i=0, nsyni-1 {
		flag=0
		while (flag==0) {
		compi=int(rf.repick())
		tmpi=rg.repick()
		dend[compi] {if (distance(tmpi)<low || distance(tmpi)>high) {flag=0} else{flag=1}}
		}
		dend[compi] {
			rsyni[i].loc(tmpi)
			}
	}

run()
}



proc runv() {
gkdr = 0.002
rc.MCellRan4(highindex+1)
	rd.MCellRan4(highindex+2)
	for i=0, nsyn-1 {
	s[i].seed(highindex+3)
	nc[i].weight = ((weight*1.e-3)/4)*3
        sh=10
	}
	for i=0, nsyn-1 {
		flag=0
		while (flag==0) {
		comp=int(rc.repick())
		tmp=rd.repick()
		dend[comp] {if (distance(tmp)<low || distance(tmp)>high) {flag=0} else{flag=1}}
		}
		dend[comp] {
			rsyn[i].loc(tmp)
			}
	}
	
	for i=0, nsyni-1 {
	si[i].seed(highindex+3)
	nci[i].weight =(weighti*1.e-3)
	}
	for i=0, nsyni-1 {
		flag=0
		while (flag==0) {
		compi=int(rf.repick())
		tmpi=rg.repick()
		dend[compi] {if (distance(tmpi)<low || distance(tmpi)>high) {flag=0} else{flag=1}}
		}
		dend[compi] {
			rsyni[i].loc(tmpi)
			}
	}

run()
}

Loading data, please wait...