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

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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, Goutagny R, Bethus I, Lopes LV, Migliore M, Marie H (2019) The Amyloid Precursor Protein C-Terminal Domain Alters CA1 Neuron Firing, Modifying Hippocampus Oscillations and Impairing Spatial Memory Encoding. Cell Rep 29:317-331.e5 [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 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;
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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 Ca L-type channel with high treshold of activation
: inserted in distal dendrites to account for distally
: restricted initiation of Ca++ spikes
: uses channel conductance (not permeability)
: written by Yiota Poirazi, 1/8/00 poirazi@LNC.usc.edu

NEURON {
	SUFFIX calH
	USEION ca READ eca WRITE ica
        RANGE gcalbar, m, h
	RANGE inf, fac, tau, mytau
}

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



PARAMETER {          : parameters that can be entered when function is called in cell-setup
        v               (mV)
        celsius = 34	(degC)
	dt              (ms)
        gcalbar = 0     (mho/cm2) : initialized conductance
	eca = 140       (mV)      : Ca++ reversal potential
      mytau (ms)
        }

STATE {	m h }                     : unknown activation and inactivation parameters to be solved in the DEs  

ASSIGNED {
	ica (mA/cm2)
      inf[2]
	tau[2]

        
}


INITIAL {
      m = 0    : initial activation parameter value
	h = 1    : initial inactivation parameter value
	rate(v)
	
}

BREAKPOINT {
	SOLVE state METHOD cnexp
	ica = gcalbar*m*m*m*h*(v - eca)

}



DERIVATIVE state {  
        rate(v)
        m' = (inf[0]-m)/tau[0]
	  h' = (inf[1]-h)/tau[1]

}

PROCEDURE rate(v (mV)) { :callable from hoc
       FROM i=0 TO 1 {
		tau[i] = vartau(v,i)
		inf[i] = varss(v,i)
	}

     
	
}


FUNCTION varss(v, i) {
	if (i==0) { 
             varss = 1 / (1 + exp((v+37)/(-1)))  : Ca activation 
	}
	else if (i==1) { 
             varss = 1 / (1 + exp((v+41)/(0.5))) : Ca inactivation 
	}
}

FUNCTION vartau(v, i) {
	if (i==0) {
          vartau = mytau  : activation variable time constant
         

        }
	else if (i==1) {
:           vartau = 25   : inactivation variable time constant
           vartau = 29   : inactivation variable time constant
        }
}	


















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