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
                            
// Artificial cells no longer need a default section.
//Network cell templates
//   AACell
// Simplified version (BPG 27-9-08)
//  - geometry and channels from Santhakumar et al 2005
//  - geometry modified to preserve VCUs different dendrites

begintemplate AACell
public is_art
public init, topol, basic_shape, subsets, geom, biophys
public pre_list, connect2target

public soma, radT2, radM2, radt2, lmM2, lmt2, radT1
public radM1, radt1, lmM1, lmt1, oriT1, oriM1, orit1
public oriT2, oriM2, orit2
public all

objref pre_list

proc init() {
  	topol()
  	subsets()
  	geom()
  	biophys()
  	geom_nseg()
  	pre_list = new List()
  	synapses()
}

create soma, radT2, radM2, radt2, lmM2, lmt2, radT1
create radM1, radt1, lmM1, lmt1, oriT1, oriM1, orit1
create oriT2, oriM2, orit2

proc topol() { local i
  	connect radT2(0), soma(1)
  	connect radM2(0), radT2(1)
  	connect radt2(0), radM2(1)
  	connect lmM2(0), radt2(1)
  	connect lmt2(0), lmM2(1)
  	connect radT1(0), soma(0)
  	connect radM1(0), radT1(1)
  	connect radt1(0), radM1(1)
  	connect lmM1(0), radt1(1)
  	connect lmt1(0), lmM1(1)
  	connect oriT1(0), soma(0)
  	connect oriM1(0), oriT1(1)
  	connect orit1(0), oriM1(1)
  	connect oriT2(0), soma(1)
  	connect oriM2(0), oriT2(1)
  	connect orit2(0), oriM2(1)
  	//basic_shape()
}

proc basic_shape() {
  	soma {pt3dclear() pt3dadd(0, 0, 0, 1) pt3dadd(15, 0, 0, 1)}
  	radT2 {pt3dclear() pt3dadd(15, 0, 0, 1) pt3dadd(45, 30, 0, 1)}
  	radM2 {pt3dclear() pt3dadd(45, 30, 0, 1) pt3dadd(75, 60, 0, 1)}
  	radt2 {pt3dclear() pt3dadd(75, 60, 0, 1) pt3dadd(90, 75, 0, 1)}
  	lmM2 {pt3dclear() pt3dadd(90, 75, 0, 1) pt3dadd(105, 90, 0, 1)}
  	lmt2 {pt3dclear() pt3dadd(105, 90, 0, 1) pt3dadd(120, 105, 0, 1)}
  	radT1 {pt3dclear() pt3dadd(0, 0, 0, 1) pt3dadd(-14, 15, 0, 1)}
  	radM1 {pt3dclear() pt3dadd(-14, 15, 0, 1) pt3dadd(-29, 30, 0, 1)}
  	radt1 {pt3dclear() pt3dadd(-29, 30, 0, 1) pt3dadd(-44, 45, 0, 1)}
  	lmM1 {pt3dclear() pt3dadd(-44, 45, 0, 1) pt3dadd(-59, 60, 0, 1)}
  	lmt1 {pt3dclear() pt3dadd(-59, 60, 0, 1) pt3dadd(-89, 90, 0, 1)}
  	oriT1 {pt3dclear() pt3dadd(0, 0, 0, 1) pt3dadd(-29, -29, 0, 1)}
  	oriM1 {pt3dclear() pt3dadd(-29, -29, 0, 1) pt3dadd(-59, -59, 0, 1)}
  	orit1 {pt3dclear() pt3dadd(-59, -59, 0, 1) pt3dadd(-89, -89, 0, 1)}
  	oriT2 {pt3dclear() pt3dadd(15, 0, 0, 1) pt3dadd(45, -29, 0, 1)}
  	oriM2 {pt3dclear() pt3dadd(45, -29, 0, 1) pt3dadd(75, -59, 0, 1)}
  	orit2 {pt3dclear() pt3dadd(75, -59, 0, 1) pt3dadd(105, -89, 0, 1)}
}

objref all
proc subsets() { local i
  	objref all
  	all = new SectionList()
    	soma all.append()
    	radT2 all.append()
    	radM2 all.append()
    	radt2 all.append()
    	lmM2 all.append()
    	lmt2 all.append()
    	radT1 all.append()
    	radM1 all.append()
    	radt1 all.append()
    	lmM1 all.append()
    	lmt1 all.append()
    	oriT1 all.append()
    	oriM1 all.append()
    	orit1 all.append()
    	oriT2 all.append()
    	oriM2 all.append()
    	orit2 all.append()

}

proc geom() {
  	forsec all {  }
  	soma {  L = 20  diam = 10  }
  	radT2 {  L = 100  diam = 4  }
  	radM2 {  L = 100  diam = 3  }
  	radt2 {  L = 200  diam = 2  }
  	lmM2 {  L = 100  diam = 1.5  }
  	lmt2 {  L = 100  diam = 1  }
  	radT1 {  L = 100  diam = 4  }
  	radM1 {  L = 100  diam = 3  }
  	radt1 {  L = 200  diam = 2  }
  	lmM1 {  L = 100  diam = 1.5  }
  	lmt1 {  L = 100  diam = 1  }
  	oriT1 {  L = 100  diam = 2  }
  	oriM1 {  L = 100  diam = 1.5  }
  	orit1 {  L = 100  diam = 1  }
  	oriT2 {  L = 100  diam = 2  }
  	oriM2 {  L = 100  diam = 1.5  }
  	orit2 {  L = 100  diam = 1  }
}

external lambda_f
proc geom_nseg() {
  	forsec all { nseg = int((L/(0.1*lambda_f(100))+.9)/2)*2 + 1  }
}

proc biophys() {

	gna = 0.15

	soma {
		insert ichan2  		
		gnatbar_ichan2 = gna  		// 0.12 //original 0.030 to .055 
		gkfbar_ichan2 = 0.013  		//original 0.015
		gl_ichan2 = 0.00018
		cm=1.4
	} 

	lmt1 {
		insert ichan2
		gnatbar_ichan2 = gna		//0.5  	//original 0.015
		gkfbar_ichan2 = 0.013
		gl_ichan2 = 0.00018
		cm=1.4
	}		

	lmt2 {
		insert ichan2
		gnatbar_ichan2 = gna		//0.5  	//original 0.015
		gkfbar_ichan2 = 0.013
		gl_ichan2 = 0.00018
		cm=1.4
	}		

	lmM1 {
		insert ichan2
		gnatbar_ichan2 = gna		//0.45  	//original 0.015
		gkfbar_ichan2 = 0.013
		gl_ichan2 = 0.00018
		cm=1.4
	}		

	lmM2 {
		insert ichan2
		gnatbar_ichan2 = gna		//0.45  	//original 0.015
		gkfbar_ichan2 = 0.013
		gl_ichan2 = 0.00018
		cm=1.4
	}		
	
	radt1 {
		insert ichan2
		gnatbar_ichan2 = gna		//0.4  	//original 0.015
		gkfbar_ichan2 = 0.013
		gl_ichan2 = 0.00018
		cm=1.4
	}		

	radt2 {
		insert ichan2
		gnatbar_ichan2 = gna		//0.4  	//original 0.015
		gkfbar_ichan2 = 0.013
		gl_ichan2 = 0.00018
		cm=1.4
	}		

	radM1 {
		insert ichan2
		gnatbar_ichan2 = gna		//0.3  	//original 0.015
		gkfbar_ichan2 = 0.013
		gl_ichan2 = 0.00018
		cm=1.4
	}		

	radM2 {
		insert ichan2
		gnatbar_ichan2 = gna		//0.3  	//original 0.015
		gkfbar_ichan2 = 0.013
		gl_ichan2 = 0.00018
		cm=1.4
	}		

	radT1 {
		insert ichan2
		gnatbar_ichan2 = gna		//0.2  	//original 0.015
		gkfbar_ichan2 = 0.013
		gl_ichan2 = 0.00018
		cm=1.4
	}		

	radT2 {
		insert ichan2
		gnatbar_ichan2 = gna		//0.2  	//original 0.015
		gkfbar_ichan2 = 0.013
		gl_ichan2 = 0.00018
		cm=1.4
	}			

	oriT1 {
		insert ichan2
		gnatbar_ichan2 = gna  		//original 0.015
		gkfbar_ichan2 = 0.013
		gl_ichan2 = 0.00018
		cm=1.4
	}		

	oriT2 {
		insert ichan2
		gnatbar_ichan2 = gna  		//original 0.015
		gkfbar_ichan2 = 0.013
		gl_ichan2 = 0.00018
		cm=1.4
	}		

	oriM1 {
		insert ichan2
		gnatbar_ichan2 = gna  		//original 0.015
		gkfbar_ichan2 = 0.013
		gl_ichan2 = 0.00018
		cm=1.4
	}		

	oriM2 {
		insert ichan2
		gnatbar_ichan2 = gna  		//original 0.015
		gkfbar_ichan2 = 0.013
		gl_ichan2 = 0.00018
		cm=1.4
	}		
	
	orit1 {
		insert ichan2
		gnatbar_ichan2 = gna  		// Sodium conductance (original 0.015)
		gkfbar_ichan2 = 0.013		// Delayed K+ rectifier (fast)
		gl_ichan2 = 0.00018		// Leak conductance
		cm=1.4
	}		

	orit2 {
		insert ichan2
		gnatbar_ichan2 = gna  		// Sodium conductance (original 0.015)
		gkfbar_ichan2 = 0.013		// Delayed K+ rectifier (fast)
		gl_ichan2 = 0.00018		// Leak conductance
		cm=1.4
	}		

	forsec all {
		insert ccanl
		catau_ccanl = 10		// Time constant for decay of intracellular Ca2+
		caiinf_ccanl = 5.e-6		// Steady-state intracellular Ca2+ concentration
		
		insert borgka
		gkabar_borgka = 0.00015		// A-type K+ conductance
		
		insert nca  			// N-type Ca2+ conductance
		gncabar_nca = 0.0008   		// check to modify- original 0.004
		
		insert lca 
		glcabar_lca = 0.005		// L-type Ca2+ conductance
		
		insert gskch
		gskbar_gskch = 0.000002		// Ca2+-dependent K (SK) conductance
		
		insert mykca
		gkbar = 0.0002			// Ca2+ and Voltage-dependent K+ (BK) conductance

//		Ra = 10.3			// 31.3 +/- 10.9
		Ra = 100			// 31.3 +/- 10.9
		enat = 55
		ekf = -90
		ek = -90
		elca = 130
		esk = -90
		el_ichan2 = -60			//-60.06
		cao_ccanl = 2
	
	} 					// make catau slower70e-3 	cao=2 cai=50.e-6

}

obfunc connect2target() { localobj nc //$o1 target point process, optional $o2 returned NetCon
  	soma nc = new NetCon(&v(1), $o1)
  	nc.threshold = -10
  	if (numarg() == 2) { $o2 = nc } // for backward compatibility
  	return nc
}

objref syn_
proc synapses() {
  	/* E0 */   lmM1 syn_ = new MyExp2Syn(0.5)  pre_list.append(syn_)	// AMPA		EC
    	syn_.tau1 = 0.5
    	syn_.tau2 = 3
    	syn_.e = 0
  	/* E1 */   lmM2 syn_ = new MyExp2Syn(0.5)  pre_list.append(syn_)	// AMPA		EC
    	syn_.tau1 = 0.5
    	syn_.tau2 = 3
    	syn_.e = 0
  	/* E2 */   radM1 syn_ = new MyExp2Syn(0.5)  pre_list.append(syn_)	// AMPA		CA3 Shaffer collateral
    	syn_.tau1 = 0.5
    	syn_.tau2 = 3
    	syn_.e = 0
  	/* E3 */   radM2 syn_ = new MyExp2Syn(0.5)  pre_list.append(syn_)	// AMPA		CA3 Shaffer collateral
    	syn_.tau1 = 0.5
    	syn_.tau2 = 3
    	syn_.e = 0
  	/* E4 */   radT1 syn_ = new MyExp2Syn(0.5)  pre_list.append(syn_)	// AMPA		CA3 Shaffer collateral
    	syn_.tau1 = 0.5
    	syn_.tau2 = 3
    	syn_.e = 0
  	/* E5 */   radT2 syn_ = new MyExp2Syn(0.5)  pre_list.append(syn_)	// AMPA		CA3 Shaffer collateral
    	syn_.tau1 = 0.5
    	syn_.tau2 = 3
    	syn_.e = 0
  	/* E6 */   oriT1 syn_ = new MyExp2Syn(0.5)  pre_list.append(syn_)	// AMPA		PC
    	syn_.tau1 = 0.5
    	syn_.tau2 = 3
    	syn_.e = 0
  	/* E7 */   oriT2 syn_ = new MyExp2Syn(0.5)  pre_list.append(syn_)	// AMPA		PC
    	syn_.tau1 = 0.5
    	syn_.tau2 = 3
    	syn_.e = 0
  	/* I8 */   soma syn_ = new MyExp2Syn(0.5)  pre_list.append(syn_)	// GABA-A	Neighboring basket cell
    	syn_.tau1 = 1
    	syn_.tau2 = 8
    	syn_.e = -75
  	/* I9 */   soma syn_ = new MyExp2Syn(0.6)  pre_list.append(syn_)	// GABA-A	Bistratified cell
    	syn_.tau1 = 1
    	syn_.tau2 = 8
    	syn_.e = -75
  	/* I10 */   oriT1 syn_ = new MyExp2Syn(0.6)  pre_list.append(syn_)	// GABA-A	Septum
    	syn_.tau1 = 1
    	syn_.tau2 = 8
    	syn_.e = -75
  	/* I11 */   oriT2 syn_ = new MyExp2Syn(0.6)  pre_list.append(syn_)	// GABA-A	Septum
    	syn_.tau1 = 1
    	syn_.tau2 = 8
    	syn_.e = -75
  	/* I12 */   oriT1 syn_ = new MyExp2Syn(0.6)  pre_list.append(syn_)	// GABA-B	Septum
    	syn_.tau1 = 35
    	syn_.tau2 = 100
    	syn_.e = -75
  	/* I13 */   oriT2 syn_ = new MyExp2Syn(0.6)  pre_list.append(syn_)	// GABA-B	Septum
    	syn_.tau1 = 35
    	syn_.tau2 = 100
    	syn_.e = -75
}

func is_art() { return 0 }

endtemplate AACell

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