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]
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 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 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 Slow Ca-dependent potassium current
                            :
                            :   Ca++ dependent K+ current IC responsible for slow AHP
                            :   Differential equations
                            :
                            :   Model based on a first order kinetic scheme
                            :
                            :       + n cai <->     (alpha,beta)
                            :
                            :   Following this model, the activation fct will be half-activated at 
                            :   a concentration of Cai = (beta/alpha)^(1/n) = cac (parameter)
                            :
                            :   The mod file is here written for the case n=2 (2 binding sites)
                            :   ---------------------------------------------
                            :
                            :   This current models the "slow" IK[Ca] (IAHP): 
                            :      - potassium current
                            :      - activated by intracellular calcium
                            :      - NOT voltage dependent
                            :
                            :   A minimal value for the time constant has been added
                            :
                            :   Ref: Destexhe et al., J. Neurophysiology 72: 803-818, 1994.
                            :   See also: http://www.cnl.salk.edu/~alain , http://cns.fmed.ulaval.ca
                            :   modifications by Yiota Poirazi 2001 (poirazi@LNC.usc.edu)
			    :   taumin = 0.5 ms instead of 0.1 ms	

                            NEURON {
                                    SUFFIX kca
                                    USEION k READ ek WRITE ik
                                    USEION ca READ cai
                                    RANGE gk, gbar, m_inf, tau_m,ik
                                    GLOBAL beta, cac
                            }


                            UNITS {
                                    (mA) = (milliamp)
                                    (mV) = (millivolt)
                                    (molar) = (1/liter)
                                    (mM) = (millimolar)
                            }


                            PARAMETER {
                                    v               (mV)
                                    celsius = 36    (degC)
                                    ek      = -80   (mV)
                                    cai     = 2.4e-5 (mM)           : initial [Ca]i
                                    gbar    = 0.01   (mho/cm2)
                                    beta    = 0.03   (1/ms)          : backward rate constant
                                    cac     = 0.025  (mM)            : middle point of activation fct
       				    taumin  = 0.5    (ms)            : minimal value of the time cst
                                    gk
                                  }


                            STATE {m}        : activation variable to be solved in the DEs       

                            ASSIGNED {       : parameters needed to solve DE 
                                    ik      (mA/cm2)
                                    m_inf
                                    tau_m   (ms)
                                    tadj
                            }
                            BREAKPOINT { 
                                    SOLVE states METHOD derivimplicit
                                    gk = gbar*m*m*m     : maximum channel conductance
                                    ik = gk*(v - ek)    : potassium current induced by this channel
                            }

                            DERIVATIVE states { 
                                    evaluate_fct(v,cai)
                                    m' = (m_inf - m) / tau_m
                            }

                            UNITSOFF
                            INITIAL {
                            :
                            :  activation kinetics are assumed to be at 22 deg. C
                            :  Q10 is assumed to be 3
                            :
                                    tadj = 3 ^ ((celsius-22.0)/10) : temperature-dependent adjastment factor
                                    evaluate_fct(v,cai)
                                    m = m_inf
                            }

                            PROCEDURE evaluate_fct(v(mV),cai(mM)) {  LOCAL car
                                    car = (cai/cac)^2
                                    m_inf = car / ( 1 + car )      : activation steady state value
                                    tau_m =  1 / beta / (1 + car) / tadj
                                    if(tau_m < taumin) { tau_m = taumin }   : activation min value of time cst
                            }
                            UNITSON

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