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

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"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."
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;
Transmitter(s): Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Aging/Alzheimer`s; Oscillations; Action Potentials; Memory;
Implementer(s): Bianchi, Daniela [danielabianchi12 -at-];
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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	calcium accumulation into a volume of area*depth next to the
	membrane with a decay (time constant tau) to resting level
	given by the global calcium variable cai0_ca_ion

	SUFFIX ccanl
USEION nca READ ncai, inca, enca WRITE enca, ncai VALENCE 2
USEION lca READ lcai, ilca, elca WRITE elca, lcai VALENCE 2
USEION tca READ tcai, itca, etca WRITE etca, tcai VALENCE 2
RANGE caiinf, catau, cai, ncai, lcai,tcai, eca, elca, enca, etca

        (mV) = (millivolt)
	(molar) = (1/liter)
	(mM) = (milli/liter)
	(mA) = (milliamp)
	FARADAY = 96520 (coul)
	R = 8.3134	(joule/degC)

INDEPENDENT {t FROM 0 TO 100 WITH 100 (ms)}

        celsius = 6.3 (degC)
	depth = 200 (nm)	: assume volume = area*depth
	catau = 9 (ms)
	caiinf = 50.e-6 (mM)	: takes precedence over cai0_ca_ion
			: Do not forget to initialize in hoc if different
			: from this default.
	cao = 2 (mM)
	ica (mA/cm2)
	inca (mA/cm2)
	ilca (mA/cm2)
	itca (mA/cm2)
	cai= 50.e-6 (mM)

	enca (mV)
	elca (mV)
	etca (mV)
	eca (mV)

	ncai (mM)
	lcai (mM)
	tcai (mM)

	ncai = _ion_ncai;
	lcai = _ion_lcai;
	tcai = _ion_tcai; 
	cai = caiinf	
	eca = ktf() * log(cao/caiinf)	
	enca = eca
	elca = eca
	etca = eca

	SOLVE integrate METHOD derivimplicit
	cai = ncai+lcai+tcai	
	eca = ktf() * log(cao/cai)	
	enca = eca
	elca = eca
	etca = eca

DERIVATIVE integrate {
ncai' = -(inca)/depth/FARADAY * (1e7) + (caiinf/3 - ncai)/catau
lcai' = -(ilca)/depth/FARADAY * (1e7) + (caiinf/3 - lcai)/catau
tcai' = -(itca)/depth/FARADAY * (1e7) + (caiinf/3 - tcai)/catau

FUNCTION ktf() (mV) {
	ktf = (1000)*R*(celsius +273.15)/(2*FARADAY)

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