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]
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 cell; Hippocampus CA1 interneuron oriens alveus 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 cell; Hippocampus CA1 interneuron oriens alveus 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 K-A channel from Klee Ficker and Heinemann
: modified by Brannon and Yiota Poirazi (poirazi@LNC.usc.edu) 
: to account for Hoffman et al 1997 distal region kinetics
: used only in locations > 100 microns from the soma
:
: modified to work with CVode by Carl Gold, 8/10/03
:  Updated by Maria Markaki  12/02/03

NEURON {
	SUFFIX kad
	USEION k READ ek WRITE ik
        RANGE gkabar,gka,ik,sh
        GLOBAL ninf,linf,taul,taun,lmin
}


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


PARAMETER {    :parameters that can be entered when function is called in cell-setup   
:	gkabar = 0.008  (mho/cm2)  :suggested conductance value
	gkabar = 0      (mho/cm2)  :initialized conductance
        vhalfn = -1     (mV)       :activation half-potential
        vhalfl = -56    (mV)       :inactivation half-potential
       a0n = 0.1       (/ms)      :parameters used
       : a0l = 0.05       (/ms)      :parameters used
        zetan = -1.8    (1)        :in calculation of
        zetal = 3       (1)        :steady state values
        gmn   = 0.39    (1)        :and time constants
        gml   = 1       (1)
	lmin  = 2       (ms)
	nmin  = 0.1     (ms)
:	nmin  = 0.2     (ms)	:suggested
	pw    = -1      (1)
	tq    = -40     (mV)
	qq    = 5       (mV)
	q10   = 5                :temperature sensitivity
     sh
}


ASSIGNED {    :parameters needed to solve DE
	v               (mV)
        ek              (mV)
	celsius  	(degC)
	ik              (mA/cm2)
        ninf
        linf      
        taul            (ms)
        taun            (ms)
        gka             (mho/cm2)
}


STATE {       :the unknown parameters to be solved in the DEs 
	n l
}

: Solve qt once in initial block
LOCAL qt

INITIAL {    :initialize the following parameter using rates()
      rates(v)
	n=ninf
	l=linf
}

BREAKPOINT {
	SOLVE states METHOD cnexp
      gka = gkabar*n*l
	ik = gka*(v-ek)
}


DERIVATIVE states {     : exact when v held constant; integrates over dt step
        rates(v)          : do this here
        n' = (ninf - n)/taun
        l' = (linf - l)/taul
}



PROCEDURE rates(v (mV)) {		 :callable from hoc
	LOCAL a,qt
        qt = q10^((celsius-24)/10)       : temprature adjastment factor
        a = alpn(v)
        ninf = 1/(1 + a)		 : activation variable steady state value
        taun = betn(v)/(qt*a0n*(1+a))	 : activation variable time constant
	if (taun<nmin) {taun=nmin}	 : time constant not allowed to be less than nmin

        a = alpl(v)
        linf = 1/(1+ a)                  : inactivation variable steady state value
	taul = 0.26(ms/mV)*(v+50)               : inactivation variable time constant
	if (taul<lmin) {taul=lmin}       : time constant not allowed to be less than lmin
}


FUNCTION alpn(v(mV)) { LOCAL zeta
  zeta = zetan+pw/(1+exp((v-tq-sh)/qq))
UNITSOFF
  alpn = exp(1.e-3*zeta*(v-vhalfn-sh)*9.648e4/(8.315*(273.16+celsius))) 
UNITSON
}

FUNCTION betn(v(mV)) { LOCAL zeta
  zeta = zetan+pw/(1+exp((v-tq-sh)/qq))
UNITSOFF
  betn = exp(1.e-3*zeta*gmn*(v-vhalfn-sh)*9.648e4/(8.315*(273.16+celsius))) 
UNITSON
}

FUNCTION alpl(v(mV)) {
UNITSOFF
  alpl = exp(1.e-3*zetal*(v-vhalfl-sh)*9.648e4/(8.315*(273.16+celsius))) 
UNITSON
}

FUNCTION betl(v(mV)) {
UNITSOFF
  betl = exp(1.e-3*zetal*gml*(v-vhalfl-sh)*9.648e4/(8.315*(273.16+celsius))) 
UNITSON
}


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