Effects of increasing CREB on storage and recall processes in a CA1 network (Bianchi et al. 2014)

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Accession:151126
Several recent results suggest that boosting the CREB pathway improves hippocampal-dependent memory in healthy rodents and restores this type of memory in an AD mouse model. However, not much is known about how CREB-dependent neuronal alterations in synaptic strength, excitability and LTP can boost memory formation in the complex architecture of a neuronal network. Using a model of a CA1 microcircuit, we investigate whether hippocampal CA1 pyramidal neuron properties altered by increasing CREB activity may contribute to improve memory storage and recall. With a set of patterns presented to a network, we find that the pattern recall quality under AD-like conditions is significantly better when boosting CREB function with respect to control. The results are robust and consistent upon increasing the synaptic damage expected by AD progression, supporting the idea that the use of CREB-based therapies could provide a new approach to treat AD.
Reference:
1 . Bianchi D, De Michele P, Marchetti C, Tirozzi B, Cuomo S, Marie H, Migliore M (2014) Effects of increasing CREB-dependent transcription on the storage and recall processes in a hippocampal CA1 microcircuit. Hippocampus 24:165-77 [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network;
Brain Region(s)/Organism:
Cell Type(s): Hippocampus CA1 pyramidal GLU cell; Hippocampus CA1 interneuron oriens alveus GABA cell; Hippocampus CA1 basket cell;
Channel(s): I Na,t; I A; I K; I M; I h; I K,Ca; I Calcium; I_AHP; I Cl, leak; Ca pump;
Gap Junctions:
Receptor(s): GabaA; GabaB; AMPA; NMDA;
Gene(s):
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON;
Model Concept(s): STDP; Aging/Alzheimer`s; Depolarization block; Storage/recall; CREB;
Implementer(s): Bianchi, Daniela [danielabianchi12 -at- gmail.com]; De Michele, Pasquale [pasquale.demichele at unina.it];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; Hippocampus CA1 interneuron oriens alveus GABA cell; GabaA; GabaB; AMPA; NMDA; I Na,t; I A; I K; I M; I h; I K,Ca; I Calcium; I_AHP; I Cl, leak; Ca pump; Gaba; Glutamate;
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Bianchietal
Results
Weights
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
axoaxonic_cell17S.hoc *
basket_cell17S.hoc *
bistratified_cell13S.hoc *
burst_cell.hoc *
HAM_SR1.ses
mosinit.hoc
olm_cell2.hoc
PureRec_phase.hoc
PureRec_phase_ser.hoc
pyramidal_cell4.hoc
ranstream.hoc *
stim_cell.hoc
Sto_phase.hoc
Sto_phase_ser.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