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 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 ichan2.mod  
 
COMMENT
konduktivitas valtozas hatasa- somaban 
ENDCOMMENT
 
UNITS {
        (mA) =(milliamp)
        (mV) =(millivolt)
        (uF) = (microfarad)
	(molar) = (1/liter)
	(nA) = (nanoamp)
	(mM) = (millimolar)
	(um) = (micron)
	FARADAY = 96520 (coul)
	R = 8.3134	(joule/degC)
}
 
? interface 
NEURON { 
SUFFIX ichan2 
USEION nat READ enat WRITE inat VALENCE 1
USEION kf READ ekf WRITE ikf  VALENCE 1
USEION ks READ eks WRITE iks  VALENCE 1
NONSPECIFIC_CURRENT il 
RANGE  gnat, gkf, gks
RANGE gnatbar, gkfbar, gksbar
RANGE gl, el
RANGE minf, mtau, hinf, htau, nfinf, nftau, inat, ikf, nsinf, nstau, iks
}
 
INDEPENDENT {t FROM 0 TO 100 WITH 100 (ms)}
 
PARAMETER {
        v (mV) 
        celsius = 6.3 (degC)
        dt (ms) 
        enat  (mV)
	gnatbar (mho/cm2)   
        ekf  (mV)
	gkfbar (mho/cm2)
        eks  (mV)
	gksbar (mho/cm2)
	gl (mho/cm2)    
 	el (mV)
}
 
STATE {
	m h nf ns
}
 
ASSIGNED {
         
        gnat (mho/cm2) 
        gkf (mho/cm2)
        gks (mho/cm2)

        inat (mA/cm2)
        ikf (mA/cm2)
        iks (mA/cm2)


	il (mA/cm2)

	minf hinf nfinf nsinf
 	mtau (ms) htau (ms) nftau (ms) nstau (ms)
	mexp hexp nfexp nsexp
} 

? currents
BREAKPOINT {
	SOLVE states
        gnat = gnatbar*m*m*m*h  
        inat = gnat*(v - enat)
        gkf = gkfbar*nf*nf*nf*nf
        ikf = gkf*(v-ekf)
        gks = gksbar*ns*ns*ns*ns
        iks = gks*(v-eks)

	il = gl*(v-el)
}
 
UNITSOFF
 
INITIAL {
	trates(v)
	
	m = minf
	h = hinf
      nf = nfinf
      ns = nsinf
	
	VERBATIM
	return 0;
	ENDVERBATIM
}

? states
PROCEDURE states() {	:Computes state variables m, h, and n 
        trates(v)	:      at the current v and dt.
        m = m + mexp*(minf-m)
        h = h + hexp*(hinf-h)
        nf = nf + nfexp*(nfinf-nf)
        ns = ns + nsexp*(nsinf-ns)
        VERBATIM
        return 0;
        ENDVERBATIM
}
 
LOCAL q10

? rates
PROCEDURE rates(v) {  :Computes rate and other constants at current v.
                      :Call once from HOC to initialize inf at resting v.
        LOCAL  alpha, beta, sum
        :q10 = 3^((celsius - 6.3)/10)
        q10 = 1		: make temperature independent (BPG)
                :"m" sodium activation system - act and inact cross at -40
	alpha = -0.3*vtrap((v+60-17),-5)
	beta = 0.3*vtrap((v+60-45),5)
	sum = alpha+beta        
	mtau = 1/sum      minf = alpha/sum
                :"h" sodium inactivation system
	alpha = 0.23/exp((v+60+5)/20)
	beta = 3.33/(1+exp((v+60-47.5)/-10))
	sum = alpha+beta
	htau = 1/sum 
        hinf = alpha/sum 
             :"ns" sKDR activation system
        alpha = -0.028*vtrap((v+65-35),-6)
	beta = 0.1056/exp((v+65-10)/40)
	sum = alpha+beta        
	nstau = 1/sum      nsinf = alpha/sum
            :"nf" fKDR activation system
        alpha = -0.07*vtrap((v+65-47),-6)
	beta = 0.264/exp((v+65-22)/40)
	sum = alpha+beta        
	nftau = 1/sum      nfinf = alpha/sum
	
}
 
PROCEDURE trates(v) {  :Computes rate and other constants at current v.
                      :Call once from HOC to initialize inf at resting v.
	LOCAL tinc
        TABLE minf, mexp, hinf, hexp, nfinf, nfexp, nsinf, nsexp, mtau, htau, nftau, nstau
	DEPEND dt, celsius FROM -100 TO 100 WITH 200
                           
	rates(v)	: not consistently executed from here if usetable_hh == 1
		: so don't expect the tau values to be tracking along with
		: the inf values in hoc

	       tinc = -dt * q10
        mexp = 1 - exp(tinc/mtau)
        hexp = 1 - exp(tinc/htau)
	nfexp = 1 - exp(tinc/nftau)
	nsexp = 1 - exp(tinc/nstau)
}
 
FUNCTION vtrap(x,y) {  :Traps for 0 in denominator of rate eqns.
        if (fabs(x/y) < 1e-6) {
                vtrap = y*(1 - x/y/2)
        }else{  
                vtrap = x/(exp(x/y) - 1)
        }
}
 
UNITSON


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