ModelDB is moving. Check out our new site at https://modeldb.science. The corresponding page is https://modeldb.science/144976.

CA1 pyramidal neurons: effects of Alzheimer (Culmone and Migliore 2012)

 Download zip file 
Help downloading and running models
Accession:144976
The model predicts possible therapeutic treatments of Alzheimers's Disease in terms of pharmacological manipulations of channels' kinetic and activation properties. The results suggest how and which mechanism can be targeted by a drug to restore the original firing conditions. The simulations reproduce somatic membrane potential in control conditions, when 90% of membrane is affected by AD (Fig.4A of the paper), and after treatment (Fig.4B of the paper).
Reference:
1 . Culmone V, Migliore M (2012) Progressive effect of beta amyloid peptides accumulation on CA1 pyramidal neurons: a model study suggesting possible treatments. Front Comput Neurosci 6:52 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Synapse; Channel/Receptor; 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):
Simulation Environment: NEURON;
Model Concept(s): Active Dendrites; Detailed Neuronal Models; Action Potentials; Aging/Alzheimer`s;
Implementer(s): Migliore, Michele [Michele.Migliore at Yale.edu]; Culmone, Viviana [viviana.abigail at hotmail.it];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; AMPA; I Na,t; I A; I K; I h;
/
alzheimer
readme.html
distr.mod *
h.mod *
kadist.mod
kaprox.mod *
kdrca1.mod *
na3n.mod *
naxn.mod *
netstims.mod *
10sim.ses
fixnseg.hoc *
geo5038804.hoc
membrane_potential.hoc
mosinit.hoc
screenshot.png
                            
TITLE nax
: Na current for axon. No slow inact.
: M.Migliore Jul. 1997
: added sh to account for higher threshold M.Migliore, Apr.2002

NEURON {
	SUFFIX nax
	USEION na READ ena WRITE ina
	RANGE  gbar, sh
	GLOBAL minf, hinf, mtau, htau,thinf, qinf
}

PARAMETER {
	sh   = 0	(mV)
	gbar = 0.010   	(mho/cm2)	
								
	tha  =  -30	(mV)		: v 1/2 for act	
	qa   = 7.2	(mV)		: act slope (4.5)		
	Ra   = 0.4	(/ms)		: open (v)		
	Rb   = 0.124 	(/ms)		: close (v)		

	thi1  = -45	(mV)		: v 1/2 for inact 	
	thi2  = -45 	(mV)		: v 1/2 for inact 	
	qd   = 1.5	(mV)	        : inact tau slope
	qg   = 1.5      (mV)
	mmin=0.02	
	hmin=0.5			
	q10=2
	Rg   = 0.01 	(/ms)		: inact recov (v) 	
	Rd   = .03 	(/ms)		: inact (v)	

	thinf  = -50 	(mV)		: inact inf slope	
	qinf  = 4 	(mV)		: inact inf slope 

	ena		(mV)            : must be explicitly def. in hoc
	celsius
	v 		(mV)
}


UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
	(pS) = (picosiemens)
	(um) = (micron)
} 

ASSIGNED {
	ina 		(mA/cm2)
	thegna		(mho/cm2)
	minf 		hinf 		
	mtau (ms)	htau (ms) 	
}
 

STATE { m h}

BREAKPOINT {
        SOLVE states METHOD cnexp
        thegna = gbar*m*m*m*h
	ina = thegna * (v - ena)
} 

INITIAL {
	trates(v,sh)
	m=minf  
	h=hinf
}

DERIVATIVE states {   
        trates(v,sh)      
        m' = (minf-m)/mtau
        h' = (hinf-h)/htau
}

PROCEDURE trates(vm,sh2) {  
        LOCAL  a, b, qt
        qt=q10^((celsius-24)/10)
	a = trap0(vm,tha+sh2,Ra,qa)
	b = trap0(-vm,-tha-sh2,Rb,qa)
	mtau = 1/(a+b)/qt
        if (mtau<mmin) {mtau=mmin}
	minf = a/(a+b)

	a = trap0(vm,thi1+sh2,Rd,qd)
	b = trap0(-vm,-thi2-sh2,Rg,qg)
	htau =  1/(a+b)/qt
        if (htau<hmin) {htau=hmin}
	hinf = 1/(1+exp((vm-thinf-sh2)/qinf))
}

FUNCTION trap0(v,th,a,q) {
	if (fabs(v-th) > 1e-6) {
	        trap0 = a * (v - th) / (1 - exp(-(v - th)/q))
	} else {
	        trap0 = a * q
 	}
}	

        


Loading data, please wait...