The APP in C-terminal domain alters CA1 neuron firing (Pousinha et al 2019)

 Download zip file   Auto-launch 
Help downloading and running models
Accession:256388
"The amyloid precursor protein (APP) is central to AD pathogenesis and we recently showed that its intracellular domain (AICD) could modify synaptic signal integration. We now hypothezise that AICD modifies neuron firing activity, thus contributing to the disruption of memory processes. Using cellular, electrophysiological and behavioural techniques, we showed that pathological AICD levels weakens CA1 neuron firing activity through a gene transcription-dependent mechanism. Furthermore, increased AICD production in hippocampal neurons modifies oscillatory activity, specifically in the gamma frequency range, and disrupts spatial memory task. Collectively, our data suggest that AICD pathological levels, observed in AD mouse models and in human patients, might contribute to progressive neuron homeostatic failure, driving the shift from normal ageing to AD."
Reference:
1 . Pousinha PA, Mouska X, Bianchi D, Temido-Ferreira M, Rajão-Saraiva J, Gomes R, Fernandez SP, Salgueiro-Pereira AR, Gandin C, Raymond EF, Barik J, Lopes LV, Migliore M, Goutagny R, Bethus I, Marie H (2019) The Amyloid Precursor Protein C-terminal domain alters CA1 neuron firing, modifying hippocampus oscillations and impairing spatial memory encoding Cell Reports, in press
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 M; I h; I L high threshold; I_AHP;
Gap Junctions:
Receptor(s): NMDA;
Gene(s):
Transmitter(s): Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Aging/Alzheimer`s; Oscillations; Action Potentials; Memory;
Implementer(s): Bianchi, Daniela [danielabianchi12 -at- gmail.com];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; NMDA; I Na,t; I L high threshold; I A; I K; I M; I h; I_AHP; Glutamate;
/
PousinhaMouskaBianchiEtAl2019
readme.txt
ANsyn.mod *
bgka.mod *
burststim2.mod *
cad.mod *
cagk.mod
cal.mod *
calH.mod *
car.mod *
cat.mod *
ccanl.mod *
d3.mod *
gskch.mod *
h.mod *
IA.mod
ichan2.mod *
Ih.mod *
kadist.mod *
kaprox.mod *
Kaxon.mod *
kca.mod *
Kdend.mod *
kdr.mod *
kdrax.mod *
km.mod *
Ksoma.mod *
LcaMig.mod *
my_exp2syn.mod *
na3.mod *
na3dend.mod *
na3notrunk.mod *
Naaxon.mod *
Nadend.mod *
nap.mod *
Nasoma.mod *
nax.mod *
nca.mod *
nmdanet.mod *
regn_stim.mod *
somacar.mod *
STDPE2Syn2.mod *
mosinit.hoc
pyramidal_cell4b.hoc
ranstream.hoc *
ses.ses
stim_cell.hoc *
testcell.hoc
                            
TITLE ichan2.mod  
 
COMMENT
konduktivitas valtozas hatasa- somaban 
ENDCOMMENT
 
UNITS {
        (mA) =(milliamp)
        (mV) =(millivolt)
        (uF) = (microfarad)
	(molar) = (1/liter)
	(nA) = (nanoamp)
	(mM) = (millimolar)
	(um) = (micron)
	FARADAY = 96520 (coul)
	R = 8.3134	(joule/degC)
}
 
? interface 
NEURON { 
SUFFIX ichan2 
USEION nat READ enat WRITE inat VALENCE 1
USEION kf READ ekf WRITE ikf  VALENCE 1
USEION ks READ eks WRITE iks  VALENCE 1
NONSPECIFIC_CURRENT il 
RANGE  gnat, gkf, gks
RANGE gnatbar, gkfbar, gksbar
RANGE gl, el
RANGE minf, mtau, hinf, htau, nfinf, nftau, inat, ikf, nsinf, nstau, iks
}
 
INDEPENDENT {t FROM 0 TO 100 WITH 100 (ms)}
 
PARAMETER {
        v (mV) 
        celsius = 6.3 (degC)
        dt (ms) 
        enat  (mV)
	gnatbar (mho/cm2)   
        ekf  (mV)
	gkfbar (mho/cm2)
        eks  (mV)
	gksbar (mho/cm2)
	gl (mho/cm2)    
 	el (mV)
}
 
STATE {
	m h nf ns
}
 
ASSIGNED {
         
        gnat (mho/cm2) 
        gkf (mho/cm2)
        gks (mho/cm2)

        inat (mA/cm2)
        ikf (mA/cm2)
        iks (mA/cm2)


	il (mA/cm2)

	minf hinf nfinf nsinf
 	mtau (ms) htau (ms) nftau (ms) nstau (ms)
	mexp hexp nfexp nsexp
} 

? currents
BREAKPOINT {
	SOLVE states
        gnat = gnatbar*m*m*m*h  
        inat = gnat*(v - enat)
        gkf = gkfbar*nf*nf*nf*nf
        ikf = gkf*(v-ekf)
        gks = gksbar*ns*ns*ns*ns
        iks = gks*(v-eks)

	il = gl*(v-el)
}
 
UNITSOFF
 
INITIAL {
	trates(v)
	
	m = minf
	h = hinf
      nf = nfinf
      ns = nsinf
	
	VERBATIM
	return 0;
	ENDVERBATIM
}

? states
PROCEDURE states() {	:Computes state variables m, h, and n 
        trates(v)	:      at the current v and dt.
        m = m + mexp*(minf-m)
        h = h + hexp*(hinf-h)
        nf = nf + nfexp*(nfinf-nf)
        ns = ns + nsexp*(nsinf-ns)
        VERBATIM
        return 0;
        ENDVERBATIM
}
 
LOCAL q10

? rates
PROCEDURE rates(v) {  :Computes rate and other constants at current v.
                      :Call once from HOC to initialize inf at resting v.
        LOCAL  alpha, beta, sum
        :q10 = 3^((celsius - 6.3)/10)
        q10 = 1		: make temperature independent (BPG)
                :"m" sodium activation system - act and inact cross at -40
	alpha = -0.3*vtrap((v+60-17),-5)
	beta = 0.3*vtrap((v+60-45),5)
	sum = alpha+beta        
	mtau = 1/sum      minf = alpha/sum
                :"h" sodium inactivation system
	alpha = 0.23/exp((v+60+5)/20)
	beta = 3.33/(1+exp((v+60-47.5)/-10))
	sum = alpha+beta
	htau = 1/sum 
        hinf = alpha/sum 
             :"ns" sKDR activation system
        alpha = -0.028*vtrap((v+65-35),-6)
	beta = 0.1056/exp((v+65-10)/40)
	sum = alpha+beta        
	nstau = 1/sum      nsinf = alpha/sum
            :"nf" fKDR activation system
        alpha = -0.07*vtrap((v+65-47),-6)
	beta = 0.264/exp((v+65-22)/40)
	sum = alpha+beta        
	nftau = 1/sum      nfinf = alpha/sum
	
}
 
PROCEDURE trates(v) {  :Computes rate and other constants at current v.
                      :Call once from HOC to initialize inf at resting v.
	LOCAL tinc
        TABLE minf, mexp, hinf, hexp, nfinf, nfexp, nsinf, nsexp, mtau, htau, nftau, nstau
	DEPEND dt, celsius FROM -100 TO 100 WITH 200
                           
	rates(v)	: not consistently executed from here if usetable_hh == 1
		: so don't expect the tau values to be tracking along with
		: the inf values in hoc

	       tinc = -dt * q10
        mexp = 1 - exp(tinc/mtau)
        hexp = 1 - exp(tinc/htau)
	nfexp = 1 - exp(tinc/nftau)
	nsexp = 1 - exp(tinc/nstau)
}
 
FUNCTION vtrap(x,y) {  :Traps for 0 in denominator of rate eqns.
        if (fabs(x/y) < 1e-6) {
                vtrap = y*(1 - x/y/2)
        }else{  
                vtrap = x/(exp(x/y) - 1)
        }
}
 
UNITSON


Loading data, please wait...