Effect of the initial synaptic state on the probability to induce LTP and LTD (Migliore et al. 2015)

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Accession:157339
NEURON mod files from the paper: M. Migliore, et al. (2015). In this paper, we investigate the possibility that the experimental protocols on synaptic plasticity may result in different consequences (e.g., LTD instead of LTP), according to the initial conditions of the stimulated synapses, and can generate confusing results. Using biophysical models of synaptic plasticity and hippocampal CA1 pyramidal neurons, we study how, why, and to what extent EPSPs observed at the soma after induction of LTP/LTD reflects the actual (local) synaptic state. The model and the results suggest a physiologically plausible explanation of why LTD induction is experimentally difficult, and they offer experimentally testable predictions on the stimulation protocols that may be more effective.
Reference:
1 . Migliore M, De Simone G, Migliore R (2015) Effect of the initial synaptic state on the probability to induce long-term potentiation and depression. Biophys J 108:1038-46 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Synapse; Dendrite;
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): AMPA;
Gene(s):
Transmitter(s): Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Long-term Synaptic Plasticity;
Implementer(s): Migliore, Michele [Michele.Migliore at Yale.edu]; Migliore, Rosanna [rosanna.migliore at cnr.it];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; AMPA; I Na,t; I A; I K; I h; Glutamate;
/
MiglioreEtAl2015
readme.html
h.mod *
kadist.mod *
kaprox.mod *
kdrca1.mod *
ltpltd.mod
na3n.mod *
naxn.mod *
netstims.mod *
fig1C.hoc
fixnseg.hoc *
geo5038804.hoc *
mosinit.hoc
screenshot.png
                            
load_file("nrngui.hoc")
cvode_active(1)




numaxon=1
numsoma=1
numbasal=52
numapical=70
numtrunk=49

xopen("geo5038804.hoc")             // geometry file
xopen("fixnseg.hoc")           

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

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

RaAll= 150
RaSoma=150  
RaAx = 50

Vrest = -65
dt = 0.1
gna =  .025
AXONM = 5
gkdr = 0.01
celsius = 35.0  
KMULT =  0.03
KMULTP = 0.03
ghd=0.00005

objref g, b,c, stim0, stim1, stim2, stim, p,  nc0, nc1, nc2, ncstim, syn


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 "dendrite"{insert pas e_pas=Vrest g_pas = 1/RmDend Ra=RaAll cm=CmDend}
forsec "user5" {insert pas e_pas=Vrest g_pas = 1/RmDend Ra=RaAll cm=CmDend}

access soma

freq=50
geom_nseg()
tot=0
forall {tot=tot+nseg}
distance()

tstop=40000

b = new VBox()
b.intercept(1)
g = new Graph()
g.size(0,tstop,-65.1,-63.5)
g.addvar("apical_dendrite[65].v(0.5)",3,1,2*tstop,0,2)
g.label(0.3,0.1,"dendritic membrane potential")
g.exec_menu("10% Zoom out")
g.xaxis(1)
c = new Graph()
c.size(0,tstop,0,4)
c.xaxis(1)
c.addexpr("syn.Np", 2, 1)
c.addexpr("syn.Nd", 4, 1)
c.exec_menu("10% Zoom out")
b.intercept(0)
b.map()


rel=0.5
soma {

stim0= new NetStim(.5)
stim0.number=1
stim0.interval=10
stim0.start=250


stim= new NetStim(.5)
stim.number=50
stim.interval=200
stim.start=1100

stim1= new NetStim(rel)
stim1.number=4
stim1.interval=10
stim1.start=1100

ncstim = new NetCon(stim, stim1, 0, 0, 0.001)

stim2 = new NetStim(.5)
stim2.number =1
stim2.interval =10
stim2.start = 35000

}

forsec "axon" {   
                insert nax gbar_nax=gna * AXONM
                insert kdr gkdrbar_kdr=gkdr
                insert kap gkabar_kap = KMULTP
}

forsec "soma" {   
		insert hd ghdbar_hd=ghd	vhalfl_hd=-73
                insert na3 gbar_na3=gna
                insert kdr gkdrbar_kdr=gkdr
                insert kap gkabar_kap = KMULTP
}

for i=0, numbasal-1 dendrite[i] {
		insert hd ghdbar_hd=ghd vhalfl_hd=-73
                insert na3 gbar_na3=gna
                insert kdr gkdrbar_kdr=gkdr
		insert kap gkabar_kap=0
		insert kad gkabar_kad=0

		for (x) if (x>0 && x<1) { xdist = distance(x)
                	ghdbar_hd(x) = ghd*(1+3*xdist/100)
                		if (xdist > 100){
					vhalfl_hd=-81
                        		gkabar_kad(x) = KMULT*(1+xdist/100)
                			} else {
					vhalfl_hd=-73
                        		gkabar_kap(x) = KMULTP*(1+xdist/100)
               				}
		}
}
                
forsec "apical_dendrite" {
		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) if (x>0 && x<1) { xdist = distance(x)
                	ghdbar_hd(x) = ghd*(1+3*xdist/100)
                		if (xdist > 100){
					vhalfl_hd=-81
                        		gkabar_kad(x) = KMULT*(1+xdist/100)
                			} else {
					vhalfl_hd=-73
                        		gkabar_kap(x) = KMULTP*(1+xdist/100)
               				} 
		}
}

numap=65
apical_dendrite[numap]{ 
syn= new ltpltd(.5)
}



nc0= new NetCon(stim0, syn, 0, 0, 0.8e-3)
nc1 = new NetCon(stim1, syn, 0, 0, 0.8e-3)
nc2= new NetCon(stim2, syn, 0, 0, 0.8e-3)




forsec "user5" {
			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) if (x>0 && x<1) { xdist = distance(x)
                	ghdbar_hd(x) = ghd*(1+3*xdist/100)
                		if (xdist > 100){
					vhalfl_hd=-81
                        		gkabar_kad(x) = KMULT*(1+xdist/100)
                			} else {
					vhalfl_hd=-73
                        		gkabar_kap(x) = KMULTP*(1+xdist/100)
               				}
		}
}

proc init() {
	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()
	cvode.event(tstop)
	access soma
	g.begin()
	c.begin()
}


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

xpanel(" ")
xlabel("  ")
xradiobutton("TBS LTP","setTBSLTP()",1)
xradiobutton("TBS LTD","setTBSLTD()")
xradiobutton("HFS LTP (50 Hz)","setHFSLTP()")
xradiobutton("LFS LTD (3 Hz)","setLFSLTD()")
xlabel("  ")
xbutton("run", "run()")
xpanel()

 

proc setTBSLTP() {
ncstim.weight=0.001
stim.number=50
stim.interval=200
stim1.number=4
stim1.interval=10
}

proc setTBSLTD() {
ncstim.weight=0.001
stim.number=10
stim.interval=1000
stim1.number=2
stim1.interval=10
}


proc setHFSLTP() {
ncstim.weight=0
stim1.number =500
stim1.interval =20	
}

proc setLFSLTD() {
ncstim.weight=0
stim1.number =30
stim1.interval =333	
}



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