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; 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; 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
                            
COMMENT

Sodium current for the soma

References:

1.	Martina, M., Vida, I., and Jonas, P.  Distal initiation and active
	propagation of action potentials in interneuron dendrites,
	Science, 287:295-300, 2000.

			soma	axon-lacking dend	axon-bearing dend
Na+	gmax	    107 ps/um2	   117 ps/um2		   107 ps/um2
	slope 	    10.9 mV/e	   11.2 mV/e		   11.2 mV/e
	V1/2        -37.8 mV       -45.6 mV                -45.6 mV



2.	Marina, M. and Jonas, P.  Functional differences in Na+ channel
	gating between fast-spiking interneurons and principal neurones of rat
	hippocampus, J. Physiol., 505.3:593-603, 1997.

*Note* The interneurons here are basket cells from the dentate gyrus.

Na+	Activation V1/2				-25.1 mV
	slope			 		11.5
	Activation t (-20 mV)	 		0.16 ms
	Deactivation t (-40 mV)	 		0.13 ms
 	Inactivation V1/2			-58.3 mV
	slope			 		6.7
	onset of inactivation t (-20 mV)	1.34 ms
	onset of inactivation t (-55 mV)	18.6 ms
	recovery from inactivation t		2.0 ms
	(30 ms conditioning pulse)
	recovery from inactivation t		2.7 ms
	(300 ms conditioning pulse)

ENDCOMMENT
UNITS {
        (mA) = (milliamp)
        (mV) = (millivolt)
}
 
NEURON {
        SUFFIX Nasoma
        USEION na READ ena WRITE ina
        NONSPECIFIC_CURRENT il
        RANGE gnasoma, gl, el, ina
        GLOBAL minf, hinf, hexp, mtau, htau
}
 
INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}
 
PARAMETER {
        v (mV)
        celsius = 24 (degC)
        dt (ms)
        gnasoma = .0107 (mho/cm2)
        ena = 90 (mV)
        gl = .00005 (mho/cm2)
        el = -70 (mV)
}
 
STATE {
        m h 
}
 
ASSIGNED {
        ina (mA/cm2)
        il (mA/cm2)
        minf 
	mexp 
	hinf 
	hexp
	mtau (ms)
	htau (ms)
}
 
INITIAL {
	m = minf
	h = hinf
}

BREAKPOINT {
        SOLVE states
	ina = gnasoma*minf*minf*minf*h*(v - ena)    
        il = gl*(v - el)
}

PROCEDURE states() {	:exact when v held constant
	evaluate_fct(v)
	h = h + hexp*(hinf - h)
	VERBATIM
	return 0;
	ENDVERBATIM 
}
UNITSOFF
PROCEDURE evaluate_fct(v(mV)) {  :Computes rate and other constants at 
		      :current v.
                      :Call once from HOC to initialize inf at resting v.
        LOCAL q10, tinc, alpha, beta
        TABLE minf, hinf, hexp, mtau, htau DEPEND dt, celsius FROM -200 TO 
100 WITH 300
:		q10 = 3^((celsius - 24)/10)
		q10 = 1	: BPG
		tinc = -dt*q10
		alpha = 0.1*vtrap(-(v+38),10)
		beta = 4*exp(-(v+63)/18)
		mtau = 1/(alpha + beta)
		minf = alpha*mtau
		alpha = 0.07*Exp(-(v+63)/20)
		beta = 1/(1+Exp(-(v+33)/10))
		htau = 1/(alpha + beta)
		hinf = alpha*htau
		hexp = 1-Exp(tinc/htau)
}
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)
		}
}
FUNCTION Exp(x) {
		if (x < -100) {
			Exp = 0
		}else{
			Exp = exp(x)
		}
}
UNITSON

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