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

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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]
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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;
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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 K-DR channel
: from Klee Ficker and Heinemann
: modified to account for Dax et al.
: M.Migliore 1997

UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)

}

PARAMETER {
	v (mV)
        ek (mV)		: must be explicitely def. in hoc
	celsius		(degC)
	gkdrbar=.003 (mho/cm2)
        vhalfn=13   (mV)
        a0n=0.02      (/ms)
        zetan=-3    (1)
        gmn=0.7  (1)
	nmax=2  (1)
	q10=1
}


NEURON {
	SUFFIX kdr
	USEION k READ ek WRITE ik
        RANGE gkdr,gkdrbar
	GLOBAL ninf,taun
}

STATE {
	n
}

ASSIGNED {
	ik (mA/cm2)
        ninf
        gkdr
        taun
}

BREAKPOINT {
	SOLVE states METHOD cnexp
	gkdr = gkdrbar*n
	ik = gkdr*(v-ek)

}

INITIAL {
	rates(v)
	n=ninf
}


FUNCTION alpn(v(mV)) {
  alpn = exp(1.e-3*zetan*(v-vhalfn)*9.648e4/(8.315*(273.16+celsius))) 
}

FUNCTION betn(v(mV)) {
  betn = exp(1.e-3*zetan*gmn*(v-vhalfn)*9.648e4/(8.315*(273.16+celsius))) 
}

DERIVATIVE states {     : exact when v held constant; integrates over dt step
        rates(v)
        n' = (ninf - n)/taun
}

PROCEDURE rates(v (mV)) { :callable from hoc
        LOCAL a,qt
        qt=q10^((celsius-24)/10)
        a = alpn(v)
        ninf = 1/(1+a)
        taun = betn(v)/(qt*a0n*(1+a))
	if (taun<nmax) {taun=nmax}
}