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
                            
COMMENT

Ih current	 - hyperpolarization-activated nonspecific Na and K channel
		 - contributes to the resting membrane potential
		 - controls the afterhyperpolarization
Reference:

1.	Maccaferri, G. and McBain, C.J. The hyperpolarization-activated current
	(Ih) and its contribution to pacemaker activity in rat CA1 hippocampal
	stratum oriens-alveus interneurons, J. Physiol. 497.1:119-130,
	1996.

		V1/2 = -84.1 mV
		   k = 10.2
		reversal potential = -32.9 +/- 1.1 mV

at -70 mV, currents were fitted by a single exponetial of t = 2.8+/- 0.76 s
at -120 mV, two exponentials were required, t1 = 186.3+/-33.6 ms 
t2 = 1.04+/-0.16 s


2.	Maccaferri, G. et al. Properties of the
	Hyperpoarization-activated current in rat hippocampal CA1 Pyramidal
	cells. J. Neurophysiol. Vol. 69 No. 6:2129-2136, 1993.

		V1/2 = -97.9 mV
		   k = 13.4
		reversal potential = -18.3 mV

3.	Pape, H.C.  Queer current and pacemaker: The
	hyperpolarization-activated cation current in neurons, Annu. Rev. 
	Physiol. 58:299-327, 1996.

		single channel conductance is around 1 pS
		average channel density is below 0.5 um-2
		0.5 pS/um2 = 0.00005 mho/cm2 = 0.05 umho/cm2		
4.	Magee, J.C. Dendritic Hyperpolarization-Activated Currents Modify
	the Integrative Properties of Hippocampal CA1 Pyramidal Neurons, J.
	Neurosci., 18(19):7613-7624, 1998

Deals with Ih in CA1 pyramidal cells.  Finds that conductance density
increases with distance from the soma.

soma g = 0.0013846 mho/cm2
dendrite g (300-350 um away) = 0.0125 mho/cm2
see Table 1 in th paper

ENDCOMMENT

 UNITS {
        (mA) = (milliamp)
        (mV) = (millivolt)
}
 
NEURON {
        SUFFIX Ih
        USEION h READ eh WRITE ih VALENCE 1
        RANGE gkhbar,ih
        GLOBAL rinf, rexp, tau_r
}
 
INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}
 
PARAMETER {
        v (mV)
        p = 5 (degC)
        dt (ms)
        gkhbar = 0.001385 (mho/cm2)			
        eh = -32.9 (mV)
}
 
STATE {
        r
}
 
ASSIGNED {
        ih (mA/cm2)
	rinf rexp
	tau_r
}
 
BREAKPOINT {
        SOLVE deriv METHOD derivimplicit
        ih = gkhbar*r*(v - eh)
}
 
INITIAL {
	rates(v)
	r = rinf
}

DERIVATIVE deriv { :Computes state variable h at current v and dt.
	rates(v)
	r' = (rinf - r)/tau_r
}

PROCEDURE rates(v) {  :Computes rate and other constants at current v.
                      :Call once from HOC to initialize inf at resting v.
        TABLE rinf, rexp, tau_r DEPEND dt, p FROM -200
TO 100 WITH 300
	rinf = 1/(1 + exp((v+84.1)/10.2))
	rexp = 1 - exp(-dt/(tau_r))
	tau_r = 100 + 1/(exp(-17.9-0.116*v)+exp(-1.84+0.09*v))
}
 
UNITSON


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