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 gskch.mod  calcium-activated potassium channel (non-voltage-dependent)

COMMENT

gsk granule

ENDCOMMENT

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

NEURON {
	SUFFIX gskch
	USEION sk READ esk WRITE isk VALENCE 1
	USEION nca READ ncai VALENCE 2
	USEION lca READ lcai VALENCE 2
	USEION tca READ tcai VALENCE 2
	RANGE gsk, gskbar, qinf, qtau, isk
}

INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}

PARAMETER {
	celsius=6.3 (degC)
	v		(mV)
	dt		(ms)
	gskbar  (mho/cm2)
	esk	(mV)
	cai (mM)
	ncai (mM)
	lcai (mM)
	tcai (mM)
}

STATE { q }

ASSIGNED {
	isk (mA/cm2) gsk (mho/cm2) qinf qtau (ms) qexp
}


BREAKPOINT {          :Computes i=g*q^2*(v-esk)
	SOLVE state
        gsk = gskbar * q*q
	isk = gsk * (v-esk)
}

UNITSOFF

INITIAL {
	cai = ncai + lcai + tcai	
	q=qinf
	rate(cai)
	VERBATIM
	ncai = _ion_ncai;
	lcai = _ion_lcai;
	tcai = _ion_tcai;
	ENDVERBATIM
}


PROCEDURE state() {  :Computes state variable q at current v and dt.
	cai = ncai + lcai + tcai
	rate(cai)
	q = q + (qinf-q) * qexp
	VERBATIM
	return 0;
	ENDVERBATIM
}

LOCAL q10
PROCEDURE rate(cai) {  :Computes rate and other constants at current v.
	LOCAL alpha, beta, tinc
	:q10 = 3^((celsius - 6.3)/10)
		:"q" activation system
	q10 = 1	: BPG
alpha = 1.25e1 * cai * cai
beta = 0.00025 

:	alpha = 0.00246/exp((12*log10(cai)+28.48)/-4.5)
:	beta = 0.006/exp((12*log10(cai)+60.4)/35)
: alpha = 0.00246/fctrap(cai)
: beta = 0.006/fctrap(cai)
	qtau = 1 / (alpha + beta)
	qinf = alpha * qtau
	tinc = -dt*q10
	qexp = 1 - exp(tinc/qtau)*q10
}

UNITSON