Amyloid-beta effects on release probability and integration at CA3-CA1 synapses (Romani et al. 2013)

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Accession:147757
The role of amyloid beta (Aß) in brain function and in the pathogenesis of Alzheimer’s disease remains elusive. Recent publications reported that an increase in Aß concentration perturbs presynaptic release in hippocampal neurons, in particular by increasing release probability of CA3-CA1 synapses. The model predics how this alteration can affect synaptic plasticity and signal integration. The results suggest that the perturbation of release probability induced by increased Aß can significantly alter the spike probability of CA1 pyramidal neurons and thus contribute to abnormal hippocampal function during Alzheimer’s disease.
Reference:
1 . Romani A, Marchetti C, Bianchi D, Leinekugel X, Poirazi P, Migliore M, Marie H (2013) Computational modeling of the effects of amyloid-beta on release probability at hippocampal synapses. Front Comput Neurosci 7:1 [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell; Synapse;
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 Calcium; I_AHP;
Gap Junctions:
Receptor(s): AMPA;
Gene(s):
Transmitter(s): Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Synaptic Plasticity; Short-term Synaptic Plasticity; Facilitation; Depression; Synaptic Integration; Aging/Alzheimer`s;
Implementer(s): Bianchi, Daniela [danielabianchi12 -at- gmail.com]; Romani, Armando [romani.armando -at- gmail.com];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; AMPA; I Na,t; I A; I K; I M; I h; I Calcium; I_AHP; Glutamate;
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RomaniEtAl2013
experiment
cad.mod *
cagk.mod *
cal.mod *
calH.mod *
car.mod *
cat.mod *
d3.mod *
h.mod *
kadist.mod *
kaprox.mod *
kca.mod *
kdr.mod *
km.mod *
na3.mod *
na3dend.mod *
na3notrunk.mod *
nap.mod *
nax.mod *
netstimmm.mod *
somacar.mod *
tmgsyn.mod
vecevent.mod
cell-setup.hoc
createNewSyn4.hoc
loadBasicModel.hoc
mosinit.hoc
session.ses
simulation.hoc
                            
TITLE Ca R-type channel with medium threshold for activation
: used in distal dendritic regions, together with calH.mod, to help
: the generation of Ca++ spikes in these regions
: uses channel conductance (not permeability)
: written by Yiota Poirazi on 11/13/00 poirazi@LNC.usc.edu
:
: updated to use CVode by Carl Gold 08/10/03
:  Updated by Maria Markaki  03/12/03

NEURON {
	SUFFIX car
	USEION ca READ cai, cao WRITE ica
:	USEION Ca WRITE iCa VALENCE 2
        RANGE gcabar, m, h,ica
	RANGE inf, fac, tau
}

UNITS {
	(mA) = (milliamp)
	(mV) = (millivolt)
	(molar) = (1/liter)
	(mM) =	(millimolar)
	FARADAY = (faraday) (coulomb)
	R = (k-mole) (joule/degC)
}


ASSIGNED {               : parameters needed to solve DE
	ica (mA/cm2)
:	iCa (mA/cm2)
        inf[2]
	tau[2]		(ms)
        v               (mV)
        celsius 	(degC)
	   
	cai             (mM)      : initial internal Ca++ concentration
	cao             (mM)      : initial external Ca++ concentration
}


PARAMETER {              : parameters that can be entered when function is called in cell-setup
        gcabar = 0      (mho/cm2) : initialized conductance
        eca = 140       (mV)      : Ca++ reversal potential

       
}  

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


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

BREAKPOINT {
	SOLVE states METHOD cnexp
	:ecar = (1e3) * (R*(celsius+273.15))/(2*FARADAY) * log (cao/cai)
	ica = gcabar*m*m*m*h*(v - eca)

}


DERIVATIVE states {
	rates(v)
	m' = (inf[0]-m)/tau[0]
	h' = (inf[1]-h)/tau[1]
}

PROCEDURE rates(v(mV)) {LOCAL a, b :rest = -70
	FROM i=0 TO 1 {
		tau[i] = vartau(v,i)
		inf[i] = varss(v,i)
	}
}




FUNCTION varss(v(mV), i) {
	if (i==0) {
	    varss = 1 / (1 + exp((v+48.5)/(-3(mV)))) : Ca activation
	}
	else if (i==1) {
             varss = 1/ (1 + exp((v+53)/(1(mV))))    : Ca inactivation
	}
}

FUNCTION vartau(v(mV), i) (ms){
	if (i==0) {
         vartau = 50(ms)  : activation variable time constant
   :       vartau = 120(ms)  : activation variable time constant
        }
	else if (i==1) {
          vartau = 5(ms)   : inactivation variable time constant
     :      vartau = 4(ms)   : inactivation variable time constant
       }
	
}