Dentate gyrus network model (Santhakumar et al 2005)

 Download zip file   Auto-launch 
Help downloading and running models
Accession:51781
Mossy cell loss and mossy fiber sprouting are two characteristic consequences of repeated seizures and head trauma. However, their precise contributions to the hyperexcitable state are not well understood. Because it is difficult, and frequently impossible, to independently examine using experimental techniques whether it is the loss of mossy cells or the sprouting of mossy fibers that leads to dentate hyperexcitability, we built a biophysically realistic and anatomically representative computational model of the dentate gyrus to examine this question. The 527-cell model, containing granule, mossy, basket, and hilar cells with axonal projections to the perforant-path termination zone, showed that even weak mossy fiber sprouting (10-15% of the strong sprouting observed in the pilocarpine model of epilepsy) resulted in the spread of seizure-like activity to the adjacent model hippocampal laminae after focal stimulation of the perforant path. See reference for more and details.
Reference:
1 . Santhakumar V, Aradi I, Soltesz I (2005) Role of mossy fiber sprouting and mossy cell loss in hyperexcitability: a network model of the dentate gyrus incorporating cell types and axonal topography. J Neurophysiol 93:437-53 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network;
Brain Region(s)/Organism: Dentate gyrus;
Cell Type(s): Dentate gyrus granule cell; Dentate gyrus mossy cell; Dentate gyrus basket cell; Dentate gyrus hilar cell;
Channel(s): I L high threshold; I T low threshold; I K; I h; I K,Ca; I Calcium; I Potassium;
Gap Junctions:
Receptor(s): GabaA; AMPA;
Gene(s):
Transmitter(s):
Simulation Environment: NEURON; neuroConstruct (web link to model);
Model Concept(s): Activity Patterns; Spatio-temporal Activity Patterns; Axonal Action Potentials; Epilepsy; Synaptic Integration;
Implementer(s): Santhakumar, Vijayalakshmi [santhavi at umdnj.edu];
Search NeuronDB for information about:  Dentate gyrus granule cell; GabaA; AMPA; I L high threshold; I T low threshold; I K; I h; I K,Ca; I Calcium; I Potassium;
Files displayed below are from the implementation
/
dentategyrusnet2005
readme.html *
bgka.mod *
CaBK.mod *
ccanl.mod *
Gfluct2.mod *
gskch.mod *
hyperde3.mod *
ichan2.mod *
LcaMig.mod *
nca.mod *
tca.mod *
DG500_M7.hoc *
dgnetactivity.jpg *
dgnettraces.jpg *
mosinit.hoc *
RI10sp.hoc
testnet.hoc
                            
// This is a fully wired network that functions with 500 Granule Cells, 15 Mossy cells, 6 Basket cells and 6 HIPP Cells
//Model is based on Santhakumar et al., 2005 Fig7. The output data replicates panels A2 and B2
//Network activity is initiated by a single artificial stimulation of the Perforant Path (PP) input to 100GCs and some MC and BCs
//NOTE: Simulations include only AMPA and GABA synapses
//NOTE: single cell templates are based on physiological data obtained in synaptic blockers
//Cells are arranged in a RING and connections are made with TOPOGRAPHIC constraints
//NOTE: This simulation includes SPROUTED connections between GC axons on to GC dendrites - not present in the normal dentate

secondorder=2
tstep=0
period=2
dt=0.1
tstop=300	//1500

// define network size
ngcell = 500
nbcell = 6
nmcell = 15
nhcell = 6
npp = 1

//**********************       GRANULE CELL         ****************************************
//Defining granule cell modified from Aradi and Holmes 1999
objref Gcell[ngcell]


	begintemplate GranuleCell


ndend1=4
ndend2=4
public  pre_list, connect_pre, subsets, is_art, is_connected
public  vbc2gc, vmc2gc, vhc2gc, vgc2bc, vbc2bc, vmc2bc, vhc2bc, vgc2mc, vbc2mc, vmc2mc, vhc2mc, vgc2hc, vmc2hc
public soma, gcdend1, gcdend2
public all, gcldend, pdend, mdend, ddend

create soma, gcdend1[ndend1], gcdend2[ndend2]
objref syn, pre_list


proc init() {
	pre_list = new List()
	subsets()
	gctemp()
	synapse()
}
objref all, gcldend, pdend, mdend, ddend
proc subsets(){ local i
	objref all, gcldend, pdend, mdend, ddend
	all = new SectionList()
		soma all.append()
		for i=0, 3 gcdend1 [i] all.append()
		for i=0, 3 gcdend2 [i] all.append()

	gcldend  = new SectionList()
		gcdend1 [0] gcldend.append()
		gcdend2 [0] gcldend.append()

	pdend  = new SectionList()
		gcdend1 [1] pdend.append()
		gcdend2 [1] pdend.append()

	mdend  = new SectionList()
		gcdend1 [2] mdend.append()
		gcdend2 [2] mdend.append()

	ddend  = new SectionList()
		gcdend1 [3] ddend.append()
		gcdend2 [3] ddend.append()
}
proc gctemp() {

	soma {nseg=1 L=16.8 diam=16.8} // changed L & diam
		
	gcdend1 [0] {nseg=1 L=50 diam=3}
	for i = 1, 3	gcdend1 [i] {nseg=1 L=150 diam=3}

	gcdend2 [0] {nseg=1 L=50 diam=3}
	for i = 1, 3	gcdend2 [i] {nseg=1 L=150 diam=3}	 	

    
	forsec all {
		insert ccanl
	catau_ccanl = 10
	caiinf_ccanl = 5.e-6
	Ra=210
	}

	soma {insert ichan2  //modified from Aradi and Soltesz 2002
	gnatbar_ichan2=0.12  
	gkfbar_ichan2=0.016  
	gksbar_ichan2=0.006
		insert borgka //KA from Aradi and Soltesz 2002
	gkabar_borgka=0.012
		insert nca  // HAV-N- Ca channel modified from Aradi and Soltesz 2002
	gncabar_nca=0.002  
		insert lca // L type Ca from Migliore et al., 1995
	glcabar_lca=0.005
		insert cat	//T-type Ca adapted from Aradi and Holmes 1999
	gcatbar_cat=0.000037
		insert gskch	//SK channel from Aradi and Soltesz 2002
	gskbar_gskch=0.001
		insert cagk 	//from Migliore et al., 1995
	gkbar_cagk=0.0006
	gl_ichan2 = 0.00004
	cm=1

} 

		forsec gcldend {insert ichan2
	gnatbar_ichan2=0.018  //original 0.015
	gkfbar_ichan2=0.004
	gksbar_ichan2=0.006
		insert nca  // HAV-N- Ca channel
	gncabar_nca=0.003  // check to modify- original 0.004
		insert lca 
	glcabar_lca=0.0075
		insert cat
	gcatbar_cat=0.000075
		insert gskch
	gskbar_gskch=0.0004
		insert cagk
	gkbar_cagk=0.0006
	gl_ichan2 = 0.00004
	cm=1}
		
		forsec pdend {insert ichan2
	gnatbar_ichan2=0.013
	gkfbar_ichan2=0.004
	gksbar_ichan2=0.006
		insert nca  // HAV-N- Ca channel
	gncabar_nca=0.001  // check to modify- original 0.004
		insert lca 
	glcabar_lca=0.0075
		insert cat
	gcatbar_cat=0.00025
		insert gskch
	gskbar_gskch=0.0002
		insert cagk
	gkbar_cagk=0.001
	gl_ichan2 = 0.000063
	cm=1.6
	}
		
	 	forsec mdend {insert ichan2
	gnatbar_ichan2=0.008
	gkfbar_ichan2=0.001
	gksbar_ichan2=0.006
		insert nca  
	gncabar_nca=0.001  
		insert lca 
	glcabar_lca=0.0005
		insert cat
	gcatbar_cat=0.0005
		insert gskch
	gskbar_gskch=0.0
		insert cagk
	gkbar_cagk=0.0024
	gl_ichan2 = 0.000063

	cm=1.6}

		forsec ddend {insert ichan2
	gnatbar_ichan2=0.0
	gkfbar_ichan2=0.001
	gksbar_ichan2=0.008
		insert nca  
	gncabar_nca=0.001  
		insert lca 
	glcabar_lca=0.0
		insert cat
	gcatbar_cat=0.001
		insert gskch
	gskbar_gskch=0.0
		insert cagk
	gkbar_cagk=0.0024
	gl_ichan2 = 0.000063
	cm=1.6}
		
	
	connect gcdend1[0](0), soma(1)
	connect gcdend2[0](0), soma(1)
	for i=1,3 {
	connect gcdend1[i](0), gcdend1[i-1](1)
	}
	for i=1,3 {
	connect gcdend2[i](0), gcdend2[i-1](1)
	}


	forsec all {enat = 45 ekf = -90 eks = -90  ek=-90  elca=130 etca=130	 esk=-90
		 el_ichan2 =-70
		cao_ccanl=2 } 

		}


	proc connect_pre() {  
	soma $o2 = new NetCon (&v(1), $o1)
	}


 // Define synapses on to GCs using 
//- an Exp2Syn object (parameters tau1 -rise, tau2 -decay, 
// time constant [ms] and e - rev potential [mV]
// delay [ms] and weight -variablr betw 0 and 1 [1 corresponding to 1 'S]


	objref syn
	proc synapse() {
	gcdend1[3] syn = new Exp2Syn(0.5) // PP syn based on data from Greg Hollrigel and Kevin Staley
	syn.tau1 = 1.5	syn.tau2 = 5.5	syn.e = 0
	pre_list.append(syn)

	gcdend2[3] syn = new Exp2Syn(0.5) // PPsyn based on Greg and Staley
	syn.tau1 = 1.5	syn.tau2 = 5.5	syn.e = 0
	pre_list.append(syn)

	gcdend1[1] syn = new Exp2Syn(0.5) // MC syn *** Estimated
	syn.tau1 = 1.5	syn.tau2 = 5.5	syn.e = 0
	pre_list.append(syn)

	gcdend2[1] syn = new Exp2Syn(0.5) // MC syn   *** Estimated
	syn.tau1 = 1.5	syn.tau2 = 5.5	syn.e = 0
	pre_list.append(syn)

	gcdend1[3] syn = new Exp2Syn(0.5) // HIPP  syn based on Harney and Jones corrected for temp
	syn.tau1 = 0.5	syn.tau2 = 6	syn.e = -70
	pre_list.append(syn)

	gcdend2[3] syn = new Exp2Syn(0.5) // HIPP syn based on Harney and Jones corrected for temp
	syn.tau1 = 0.5	syn.tau2 = 6	syn.e = -70
	pre_list.append(syn)

	soma syn = new Exp2Syn(0.5) // BC  syn syn based on Bartos
	syn.tau1 = 0.26	syn.tau2 = 5.5	syn.e = -70
	pre_list.append(syn)

	gcdend1[1] syn = new Exp2Syn(0.5) // NOTE: SPROUTED SYNAPSE based on Molnar and Nadler
	syn.tau1 = 1.5	syn.tau2 = 5.5	syn.e = 0
	pre_list.append(syn)

	gcdend2[1] syn = new Exp2Syn(0.5) // NOTE: SPROUTED SYNAPSE
	syn.tau1 = 1.5	syn.tau2 = 5.5	syn.e = 0
	pre_list.append(syn)


// Total of 7 synapses per GC 0,1 PP; 	2,3 MC;	4,5 HIPP and 	6 BC	7,8 Sprout
	}
	func is_art() { return 0 }

	endtemplate GranuleCell
// *********     BASKET CELL     **************************************

// Define Basket Cell template
objref Bcell[nbcell]

	begintemplate BasketCell
ndend1=4
ndend2=4
ndend3=4
ndend4=4

public  pre_list, connect_pre, subsets, is_art, is_connected
public vbc2gc, vmc2gc, vhc2gc, vgc2bc, vbc2bc, vmc2bc, vhc2bc, vgc2mc, vbc2mc, vmc2mc, vhc2mc, vgc2hc, vmc2hc
public soma, bcdend1, bcdend2, bcdend3, bcdend4
public all, adend, bdend, cdend, ddend
create soma, bcdend1[ndend1], bcdend2[ndend2], bcdend3[ndend3], bcdend4[ndend4]
objref syn, pre_list



objref syn
proc init() {
	pre_list = new List()
	subsets()
	temp()
	synapse()
}

objref all, adend, bdend, cdend, ddend

proc subsets() { local i
	objref all, adend, bdend, cdend, ddend
	all = new SectionList()
		soma all.append()
		for i=0, 3 bcdend1 [i] all.append()
		for i=0, 3 bcdend2 [i] all.append()
		for i=0, 3 bcdend3 [i] all.append()
		for i=0, 3 bcdend4 [i] all.append()

	adend  = new SectionList()
		bcdend1 [0] adend.append()
		bcdend2 [0] adend.append()
		bcdend3 [0] adend.append()
		bcdend4 [0] adend.append()

	bdend  = new SectionList()
		bcdend1 [1] bdend.append()
		bcdend2 [1] bdend.append()
		bcdend3 [1] bdend.append()
		bcdend4 [1] bdend.append()

	cdend  = new SectionList()
		bcdend1 [2] cdend.append()
		bcdend2 [2] cdend.append()
		bcdend3 [2] cdend.append()
		bcdend4 [2] cdend.append()

	ddend  = new SectionList()
		bcdend1 [3] ddend.append()
		bcdend2 [3] ddend.append()
		bcdend3 [3] ddend.append()
		bcdend4 [3] ddend.append()
}

proc temp() {

	soma {nseg=1 L=20 diam=15} // changed L & diam
		
	bcdend1 [0] {nseg=1 L=75 diam=4}	// bcdend 1 and 2 are apical
	bcdend1 [1] {nseg=1 L=75 diam=3}
	bcdend1 [2] {nseg=1 L=75 diam=2}
 	bcdend1 [3] {nseg=1 L=75 diam=1}

	bcdend2 [0] {nseg=1 L=75 diam=4}
	bcdend2 [1] {nseg=1 L=75 diam=3}
	bcdend2 [2] {nseg=1 L=75 diam=2}
	bcdend2 [3] {nseg=1 L=75 diam=1}
 		 
	bcdend3 [0] {nseg=1 L=50 diam=4} 	// bcdend 3 and 4 are basal
	bcdend3 [1] {nseg=1 L=50 diam=3}
	bcdend3 [2] {nseg=1 L=50 diam=2}
	bcdend3 [3] {nseg=1 L=50 diam=1} 
	
	bcdend4 [0] {nseg=1 L=50 diam=4}
	bcdend4 [1] {nseg=1 L=50 diam=3}
	bcdend4 [2] {nseg=1 L=50 diam=2}
	bcdend4 [3] {nseg=1 L=50 diam=1} 	

    
	forsec all {
		insert ccanl
	catau_ccanl = 10
	caiinf_ccanl = 5.e-6
		insert borgka
	gkabar_borgka=0.00015
		insert nca  
	gncabar_nca=0.0008   
		insert lca 
	glcabar_lca=0.005
		insert gskch
	gskbar_gskch=0.000002
		insert cagk
	gkbar_cagk=0.0002
	}

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

	forsec adend {insert ichan2
	gnatbar_ichan2=0.12  //original 0.015
	gkfbar_ichan2=0.013
	gl_ichan2 = 0.00018
	cm=1.4
	}		
	forsec	bdend {insert ichan2
	gnatbar_ichan2=0.0
	gkfbar_ichan2=0.00
	gl_ichan2 = 0.00018
	cm=1.4}
		
	forsec 	cdend {insert ichan2
	gnatbar_ichan2=0.0
	gkfbar_ichan2=0.00
	gl_ichan2 = 0.00018
	cm=1.4}

	forsec	ddend {insert ichan2
	gnatbar_ichan2=0.0
	gkfbar_ichan2=0.00
	gl_ichan2 = 0.00018
	cm=1.4}


	connect bcdend1[0](0), soma(1)
	connect bcdend2[0](0), soma(1)
	connect bcdend3[0](0), soma(0)
	connect bcdend4[0](0), soma(0)
	for i=1,3 {
	connect bcdend1[i](0), bcdend1[i-1](1)
	}
	for i=1,3 {
	connect bcdend2[i](0), bcdend2[i-1](1)
	}
	for i=1,3 {
	connect bcdend3[i](0), bcdend3[i-1](1)
	}
	for i=1,3 {
	connect bcdend4[i](0), bcdend4[i-1](1)
	}


	forsec all {Ra=100}
	forsec all {enat = 55 ekf = -90  ek=-90  elca=130	esk=-90
		 el_ichan2 =-60.06
		cao_ccanl=2 }  
		}

//Defining Synapses on to Basket Cells
	objref syn  
	proc synapse() {

	bcdend1 [3] syn = new Exp2Syn(0.5)	//PP(AMPA) syn to apical dist dend Dingledine '95
	syn.tau1 = 2	syn.tau2 = 6.3	syn.e = 0 
	pre_list.append(syn)

	bcdend2 [3] syn = new Exp2Syn(0.5)	//PP(AMPA) syn to apical dist dend Dingledine '95
	syn.tau1 = 2	syn.tau2 = 6.3	syn.e = 0  
	pre_list.append(syn)

	bcdend1 [0] syn = new Exp2Syn(0.5)	//GC(AMPA) syn to prox dend Geiger '97
	syn.tau1 = .3	syn.tau2 = .6	syn.e = 0
	pre_list.append(syn)

	bcdend2 [0] syn = new Exp2Syn(0.5)	//GC(AMPA) syn to prox dend Geiger '97
	syn.tau1 = .3	syn.tau2 = .6	syn.e = 0
	pre_list.append(syn)

	bcdend3 [0] syn = new Exp2Syn(0.5)	//GC(AMPA) syn to prox dend Geiger '97
	syn.tau1 = .3	syn.tau2 = .6	syn.e = 0
	pre_list.append(syn)

	bcdend4 [0] syn = new Exp2Syn(0.5)	//GC(AMPA) syn to prox dend Geiger '97
	syn.tau1 = .3	syn.tau2 = .6	syn.e = 0
	pre_list.append(syn)

	bcdend1 [1] syn = new Exp2Syn(0.5)	//MC(AMPA) syn to apical IML dend
	syn.tau1 = 0.9	syn.tau2 = 3.6	syn.e = 0 // *** Estimated based on CA3>BC min stim Dingledine '95
	pre_list.append(syn)

	bcdend2 [1] syn = new Exp2Syn(0.5)	//MC(AMPA) syn to apical IML dend
	syn.tau1 = 0.9	syn.tau2 = 3.6	syn.e = 0 // *** Estimated based on CA3>BC min stim Dingledine '95
	pre_list.append(syn)

	bcdend1 [1] syn = new Exp2Syn(0.5)	//BC(GABA) syn to apical IML dend Bartos
	syn.tau1 = 0.16		syn.tau2 = 1.8	syn.e = -70
	pre_list.append(syn)

	bcdend2 [1] syn = new Exp2Syn(0.5)	//BC(GABA) syn to apical IML dend Bartos
	syn.tau1 = 0.16		syn.tau2 = 1.8	syn.e = -70
	pre_list.append(syn)

	bcdend1 [3] syn = new Exp2Syn(0.5)	//HIPP(GABA) syn to apical distal dend 
	syn.tau1 = 0.4	syn.tau2 = 5.8	syn.e = -70 // *** Estimated as HIPP>GC
	pre_list.append(syn)

	bcdend2 [3] syn = new Exp2Syn(0.5)	//HIPP(GABA) syn to apical distal dend 
	syn.tau1 = 0.4	syn.tau2 = 5.8	syn.e = -70 // *** Estimated as HIPP>GC
	pre_list.append(syn)

// Total of 12 synapses 	0,1 PP; 	2-5 GC; 	6,7 MC; 	8,9 BC; 	10,11 HIPP 
	}

	proc connect_pre() {  
	soma $o2 = new NetCon (&v(1), $o1)
	}

	func is_art()  { return 0 }

	endtemplate BasketCell


//****************     MOSSY CELL     ***********************************************************
//Define Mossy Cell template
//NOTE that fluctuating conductance fl can be included to simulate low input resistance in the absence of synaptic blockers Ratzliff et al., 2004

objref Mcell[nmcell]

	begintemplate MossyCell
ndend1=4
ndend2=4
ndend3=4
ndend4=4

public  pre_list, connect_pre, subsets, is_art, is_connected
public vbc2gc, vmc2gc, vhc2gc, vgc2bc, vbc2bc, vmc2bc, vhc2bc, vgc2mc, vbc2mc, vmc2mc, vhc2mc, vgc2hc, vmc2hc
public soma, mcdend1, mcdend2, mcdend3, mcdend4
create soma, mcdend1[ndend1], mcdend2[ndend2], mcdend3[ndend3], mcdend4[ndend4]
public all, adend, bdend, cdend, ddend
objref syn, pre_list, fl

//to include steady state current injection
nst=10
	objectvar stim[nst]
double stimdur[nst], stimdel[nst], stimamp[nst]
public stim, stimdur, stimamp, stimdel


objref syn
proc init() {
	pre_list = new List()
	subsets()
	temp()
	synapse()
}

objref all, pdend, ddend

proc subsets() { local i
	objref all, pdend, ddend
	all = new SectionList()
		soma all.append()
		for i=0, 3 mcdend1 [i] all.append()
		for i=0, 3 mcdend2 [i] all.append()
		for i=0, 3 mcdend3 [i] all.append()
		for i=0, 3 mcdend4 [i] all.append()

	pdend  = new SectionList()
		mcdend1 [0] pdend.append()
		mcdend2 [0] pdend.append()
		mcdend3 [0] pdend.append()
		mcdend4 [0] pdend.append()

	ddend  = new SectionList()
		for i=1, 3 mcdend1 [i] ddend.append()
		for i=1, 3 mcdend2 [i] ddend.append()
		for i=1, 3 mcdend3 [i] ddend.append()
		for i=1, 3 mcdend4 [i] ddend.append()
	
}


proc temp() {

	soma {nseg=1 L=20 diam=20} 
		
	mcdend1 [0] {nseg=1 L=50 diam=5.78}
	mcdend1 [1] {nseg=1 L=50 diam=4}
	mcdend1 [2] {nseg=1 L=50 diam=2.5}
 	mcdend1 [3] {nseg=1 L=50 diam=1}

	mcdend2 [0] {nseg=1 L=50 diam=5.78}
	mcdend2 [1] {nseg=1 L=50 diam=4}
	mcdend2 [2] {nseg=1 L=50 diam=2.5}
	mcdend2 [3] {nseg=1 L=50 diam=1}
 		 
	mcdend3 [0] {nseg=1 L=50 diam=5.78}
	mcdend3 [1] {nseg=1 L=50 diam=4}
	mcdend3 [2] {nseg=1 L=50 diam=2.5}
	mcdend3 [3] {nseg=1 L=50 diam=1} 
	
	mcdend4 [0] {nseg=1 L=50 diam=5.78}
	mcdend4 [1] {nseg=1 L=50 diam=4}
	mcdend4 [2] {nseg=1 L=50 diam=2.5}
	mcdend4 [3] {nseg=1 L=50 diam=1} 	

    
	forall {
		insert ccanl
	catau_ccanl = 10
	caiinf_ccanl = 5.e-6
		insert borgka
	gkabar_borgka=0.00001
		insert nca  
	gncabar_nca=0.00008  
		insert lca 
	glcabar_lca=0.0006
		insert gskch
	gskbar_gskch=0.016
		insert cagk
	gkbar_cagk=0.0165
		insert hyperde3 //Ih mechanism from contro Ih in Chen et al., 2001
	ghyfbar_hyperde3=0.000005
	ghysbar_hyperde3=0.000005
	}

	soma {insert ichan2  
	gnatbar_ichan2=0.12  
	gkfbar_ichan2=0.0005  
	gl_ichan2 = 0.000011
	cm=0.6} 

	forsec pdend {insert ichan2
	gnatbar_ichan2=0.12  
	gkfbar_ichan2=0.0005
	gl_ichan2 = 0.000044
	cm=2.4}
		
	forsec ddend {insert ichan2
	gnatbar_ichan2=0.0
	gkfbar_ichan2=0.00
	gl_ichan2 = 0.000044
	cm=2.4}
		
	connect mcdend1[0](0), soma(1)
	connect mcdend2[0](0), soma(1)
	connect mcdend3[0](0), soma(0)
	connect mcdend4[0](0), soma(0)
	for i=1,3 {connect mcdend1[i](0), mcdend1[i-1](1)}
	for i=1,3 {connect mcdend2[i](0), mcdend2[i-1](1)}
	for i=1,3 {connect mcdend3[i](0), mcdend3[i-1](1)}
	for i=1,3 {connect mcdend4[i](0), mcdend4[i-1](1)}

	forall {Ra=100}
	forall {enat = 55 ekf = -90  ek=-90  esk=-90 elca=130
		ehyf=-40 ehys=-40
		 el_ichan2 =-59
		cao_ccanl=2 } 

// CURRENT INJECTION
//for i=0,0 {
//stimdel[i]=1
//stimdur[i]=300
//stimamp[i]=0.65 // to reproduce 2-4Hz firing in vitro in the presence of baseline fluctuations
//soma stim[i] = new IClamp(0.5)
//stim.del[i]=stimdel[i]
//stim.dur[i]=stimdur[i]
//stim.amp[i]=stimamp[i]
//}

// FLUCTUATING CONDUCTANCE DESTEXHE ET AL., 2001
//objref fl
//soma fl = new Gfluct2(0.5)
//fl.g_e0 = 0.0242
//fl.g_i0 = 0.1146
//fl.std_e = 0.0375
//fl.std_i = 0.01875


		}

//Defining synapses on to Mossy Cells
	objref syn  
	proc synapse() {

	mcdend1 [3] syn = new Exp2Syn(0.7)	//PP(AMPA) syn to dist dend similar to PP to GC
	syn.tau1 = 1.5	syn.tau2 = 5.5	syn.e = 0
	pre_list.append(syn)

	mcdend2 [3] syn = new Exp2Syn(0.7)	//PP(AMPA) syn to dist dend similar to PP to GC
	syn.tau1 = 1.5	syn.tau2 = 5.5	syn.e = 0
	pre_list.append(syn)

	mcdend3 [3] syn = new Exp2Syn(0.7)	//PP(AMPA) syn to dist dend similar to PP to GC
	syn.tau1 = 1.5	syn.tau2 = 5.5	syn.e = 0
	pre_list.append(syn)

	mcdend4 [3] syn = new Exp2Syn(0.7)	//PP(AMPA) syn to dist dend similar to PP to GC
	syn.tau1 = 1.5	syn.tau2 = 5.5	syn.e = 0
	pre_list.append(syn)

	mcdend1 [0] syn = new Exp2Syn(0.5)	//GC(AMPA) syn to prox dend similar to GC>CA3 Jonas '93
	syn.tau1 = 0.5	syn.tau2 = 6.2	syn.e = 0
	pre_list.append(syn)

	mcdend2 [0] syn = new Exp2Syn(0.5)	//GC(AMPA) syn to prox dend similar to GC>CA3 Jonas '93
	syn.tau1 = 0.5	syn.tau2 = 6.2	syn.e = 0
	pre_list.append(syn)

	mcdend3 [0] syn = new Exp2Syn(0.5)	//GC(AMPA) syn to prox dend similar to GC>CA3 Jonas '93
	syn.tau1 = 0.5	syn.tau2 = 6.2	syn.e = 0
	pre_list.append(syn)

	mcdend4 [0] syn = new Exp2Syn(0.5)	//GC(AMPA) syn to prox dend similar to GC>CA3 Jonas '93
	syn.tau1 = 0.5	syn.tau2 = 6.2	syn.e = 0
	pre_list.append(syn)

	mcdend1 [0] syn = new Exp2Syn(0.5)	//MC(AMPA) syn to prox dend similar to CA#>CA3 Aaron
	syn.tau1 = 0.45 	syn.tau2 =2.2	syn.e = 0
	pre_list.append(syn)

	mcdend2 [0] syn = new Exp2Syn(0.5)	//MC(AMPA) syn to prox dend similar to CA#>CA3 Aaron
	syn.tau1 = 0.45	syn.tau2 = 2.2		syn.e = 0
	pre_list.append(syn)

	mcdend3 [0] syn = new Exp2Syn(0.5)	//MC(AMPA) syn to prox dend similar to CA#>CA3 Aaron
	syn.tau1 = 0.45	syn.tau2 = 2.2	syn.e = 0
	pre_list.append(syn)

	mcdend4 [0] syn = new Exp2Syn(0.5)	//MC(AMPA) syn to prox dend similar to CA#>CA3 Aaron
	syn.tau1 = 0.45	syn.tau2 = 2.2	syn.e = 0
	pre_list.append(syn)

	soma syn = new Exp2Syn(0.5)	//BC(GABA) syn to prox dend based on BC>CA3 Bartos PNAS (mice)
	syn.tau1 = 0.3	syn.tau2 = 3.3	syn.e = -70
	pre_list.append(syn)

	mcdend1 [2] syn = new Exp2Syn(0.5)	//HIPP(GABA) syn to prox dend based on Hilar>GC Harney&Jones
	syn.tau1 = .5	syn.tau2 = 6		syn.e = -70
	pre_list.append(syn)

	mcdend2 [2] syn = new Exp2Syn(0.5)	//HIPP(GABA) syn to prox dend based on Hilar>GC Harney&Jones
	syn.tau1 = .5	syn.tau2 = 6		syn.e = -70
	pre_list.append(syn)

	mcdend3 [2] syn = new Exp2Syn(0.5)	//HIPP(GABA) syn to prox dend based on Hilar>GC Harney&Jones
	syn.tau1 = .5	syn.tau2 = 6		syn.e = -70
	pre_list.append(syn)

	mcdend4 [2] syn = new Exp2Syn(0.5)	//HIPP(GABA) syn to prox dend based on Hilar>GC Harney&Jones
	syn.tau1 = .5	syn.tau2 = 6	syn.e =-70
	pre_list.append(syn)

	

// Total of 17 synapses 	0-3 PP; 	4-7 GC; 	8-11 MC; 	12 BC; 	13-16 HIPP 
	}

	proc connect_pre() {  
	soma $o2 = new NetCon (&v(1), $o1)
	}

	func is_art()  { return 0 }

	endtemplate MossyCell

//***************    HIPP CELL      ****************************

// Define HIPP CELL template
objref Hcell[nhcell]

	begintemplate HIPPCell

ndend1=3
ndend2=3
ndend3=3
ndend4=3
public  pre_list, connect_pre, subsets, is_art, is_connected
public vbc2gc, vmc2gc, vhc2gc, vgc2bc, vbc2bc, vmc2bc, vhc2bc, vgc2mc, vbc2mc, vmc2mc, vhc2mc, vgc2hc, vmc2hc
public soma, hcdend1, hcdend2, hcdend3, hcdend4
create soma, hcdend1[ndend1], hcdend2[ndend2], hcdend3[ndend3], hcdend4[ndend4]
public all, pdend, ddend
objref syn, pre_list


objref syn
proc init() {
	pre_list = new List()
	subsets()
	temp()
	synapse()
}

objref all, pdend, ddend

proc subsets() { local i
	objref all, pdend, ddend
	all = new SectionList()
		soma all.append()
		for i=0, 2 hcdend1 [i] all.append()
		for i=0, 2 hcdend2 [i] all.append()
		for i=0, 2 hcdend3 [i] all.append()
		for i=0, 2 hcdend4 [i] all.append()

	pdend  = new SectionList()
		hcdend1 [0] pdend.append()
		hcdend2 [0] pdend.append()
		hcdend3 [0] pdend.append()
		hcdend4 [0] pdend.append()

	ddend  = new SectionList()
		for i=1, 2 hcdend1 [i] ddend.append()
		for i=1, 2 hcdend2 [i] ddend.append()
		for i=1, 2 hcdend3 [i] ddend.append()
		for i=1, 2 hcdend4 [i] ddend.append()
}

proc temp() {

	soma {nseg=1 L=20 diam=10} 
		
	hcdend1 [0] {nseg=1 L=75 diam=3}
	hcdend1 [1] {nseg=1 L=75 diam=2}
	hcdend1 [2] {nseg=1 L=75 diam=1}

	hcdend2 [0] {nseg=1 L=75 diam=3}
	hcdend2 [1] {nseg=1 L=75 diam=2}
	hcdend2 [2] {nseg=1 L=75 diam=1}
 		 
	hcdend3 [0] {nseg=1 L=50 diam=3}
	hcdend3 [1] {nseg=1 L=50 diam=2}
	hcdend3 [2] {nseg=1 L=50 diam=1}
	
	hcdend4 [0] {nseg=1 L=50 diam=3}
	hcdend4 [1] {nseg=1 L=50 diam=2}
	hcdend4 [2] {nseg=1 L=50 diam=1}	

    
	forall {
		insert ccanl
	catau_ccanl = 10
	caiinf_ccanl = 5.e-6
		insert borgka
	gkabar_borgka=0.0008
		insert nca  
	gncabar_nca=0.0  
		insert lca
	glcabar_lca=0.0015
		insert gskch
	gskbar_gskch=0.003
		insert cagk
	gkbar_cagk=0.003
		insert hyperde3
	ghyfbar_hyperde3=0.000015
	ghysbar_hyperde3=0.000015
	}

	soma {insert ichan2  
	gnatbar_ichan2=0.2
	gkfbar_ichan2=0.006  
	gl_ichan2 = 0.000036
	cm=1.1} 

	forsec pdend {insert ichan2
	gnatbar_ichan2=0.2  
	gkfbar_ichan2=0.006
	gl_ichan2 = 0.000036
	cm=1.1}
		
	forsec ddend {insert ichan2
	gnatbar_ichan2=0.0
	gkfbar_ichan2=0.00
	gl_ichan2 = 0.000036
	cm=1.1}

	connect hcdend1[0](0), soma(1)
	connect hcdend2[0](0), soma(1)
	connect hcdend3[0](0), soma(0)
	connect hcdend4[0](0), soma(0)
	for i=1,2 {connect hcdend1[i](0), hcdend1[i-1](1)}
	for i=1,2 {connect hcdend2[i](0), hcdend2[i-1](1)}
	for i=1,2 {connect hcdend3[i](0), hcdend3[i-1](1)}
	for i=1,2 {connect hcdend4[i](0), hcdend4[i-1](1)}

	forall {Ra=100}
	forall {enat = 55 ekf = -90  ek=-90  esk=-90 elca=130
		 el_ichan2 =-70.45	ehyf=-40 ehys=-40
		cao_ccanl=2 }  
		}

// Defining synapses on to HIPP cells

	objref syn  
	proc synapse() {

	hcdend1 [0] syn = new Exp2Syn(0.5)	//GC(AMPA) syn to prox dend similar to GC>BC
	syn.tau1 = .3	syn.tau2 = .6	syn.e = 0
	pre_list.append(syn)

	hcdend2 [0] syn = new Exp2Syn(0.5)	//GC(AMPA) syn to prox dend similar to GC>BC
	syn.tau1 = .3	syn.tau2 = .6	syn.e = 0
	pre_list.append(syn)

	hcdend3 [0] syn = new Exp2Syn(0.5)	//GC(AMPA) syn to prox dend similar to GC>BC
	syn.tau1 = .3 syn.tau2 = .6	syn.e = 0
	pre_list.append(syn)

	hcdend4 [0] syn = new Exp2Syn(0.5)	//GC(AMPA) syn to prox dend similar to GC>BC
	syn.tau1 = .3	syn.tau2 = .6	syn.e = 0
	pre_list.append(syn)

	hcdend1 [1] syn = new Exp2Syn(0.5)	//MC(AMPA) syn to mid dend similar to CA3>int Aaron
	syn.tau1 = .9	syn.tau2 = 3.6	syn.e = 0 //*** Assumed data at physio temp
	pre_list.append(syn)

	hcdend2 [1] syn = new Exp2Syn(0.5)	//MC(AMPA) syn to mid dend similar to CA3>int Aaron
	syn.tau1 = 0.9	syn.tau2 = 3.6	syn.e = 0 //*** Assumed data at physio temp
	pre_list.append(syn)

	hcdend3 [1] syn = new Exp2Syn(0.5)	//MC(AMPA) syn to mid dend similar to CA3>int Aaron
	syn.tau1 = 0.9	syn.tau2 = 3.6	syn.e = 0  //*** Assumed data at physio temp
	pre_list.append(syn)

	hcdend4 [1] syn = new Exp2Syn(0.5)	//MC(AMPA) syn to mid dend similar to CA3>int Aaron
	syn.tau1 = 0.9		syn.tau2 = 3.6 	syn.e = 0  //*** Assumed data at physio temp
	pre_list.append(syn)

// Total of 12 synapses 	0-3 PP; 	4-7 GC; 	8-11 MC	
	}

	proc connect_pre() {  
	soma $o2 = new NetCon (&v(1), $o1)
	}

	func is_art()  { return 0 }


	endtemplate HIPPCell
//**********   Perforant Path Stimulus   ***********************************************

//Define artificial stimulus to activate PP
objref PPSt[npp]

	begintemplate PPstim

	public pp, connect_pre, is_art, acell
	create acell
	objref pp

	proc init() {
		actemp() 		
	}
		proc actemp() {
				acell pp = new NetStim(.5)
				pp.interval = 100
				pp.number = 1
				pp.start = 5
				}

	func is_art() {return 1}
	proc connect_pre() {acell $o2 = new NetCon(pp, $o1)}

	endtemplate PPstim
//###############################################################################################################
//############## CONNECTING THE CELLS  #############################
	
// NETWORK SPECIFICATION INTERFACE
	for i=0, ngcell-1 {Gcell[i] = new GranuleCell(i)}
	for i=0, nbcell-1 {Bcell[i] = new BasketCell(i)}
	for i=0, nmcell-1 {Mcell[i] = new MossyCell(i)}
	for i=0, nhcell-1 {Hcell[i] = new HIPPCell(i)}
	for i =0, npp-1 {PPSt[i] = new PPstim(i)}

objref nclist, netcon, cells, net_c, net_d, net_gr,  net_bc,  net_mc,  net_hc,  vbc2gc, vmc2gc, vhc2gc
{  cells = new List()
nclist = new List()
}

// Include all cells in cells
 func cell_append() {cells.append($o1) 
	return cells.count -1}

func nc_append() {

	if ($3 >= 0 )	{
		cells.object($1).connect_pre(cells.object($2).pre_list.object($3),netcon)
		netcon.weight = $4	netcon.delay = $5	netcon.threshold = $6
	} 
	nclist.append(netcon)
	return nclist.count-1
		}
// To check for preexisting connections between randomly selected cells
//to avoid multiple contacts between same 2 cells
func is_connected() {local i, c
	c=0
	for i=0, nclist.count-1 {
	net_c= nclist.object(i)
	if (($o1 == net_c.postcell())  && ($o2 == net_c.precell())) {c=1}
}
return c
}


objref vbc2gc, vmc2gc, vhc2gc, vgc2bc, vbc2bc, vmc2bc, vhc2bc, vgc2mc, vbc2mc, vmc2mc, vhc2mc, vgc2hc, vmc2hc,vgc2gc

//To delete certain randomly selected cells from net - in this case 8 of 15 MCs
objref killMC
	{
	vgc2bc = new Vector(nbcell, 0) //defines vectors for each "pre2post" pair, vector length is same as number of post cells fills with 0
	vbc2bc = new Vector(nbcell, 0)
	vmc2bc = new Vector(nbcell, 0)
	vhc2bc = new Vector(nbcell, 0)

//To delete certain randomly selected cells from net - in this case 8 of 15 MCs
	killMC = new Vector(8, 0)
	vgc2mc = new Vector(nmcell, 0)
	vbc2mc = new Vector(nmcell, 0)
	vmc2mc = new Vector(nmcell, 0)
	vhc2mc = new Vector(nmcell, 0)


	vgc2hc = new Vector(nhcell, 0)
	vmc2hc = new Vector(nhcell, 0)

	vbc2gc = new Vector(ngcell, 0)
	vmc2gc = new Vector(ngcell, 0)
	vhc2gc = new Vector(ngcell, 0)
	vgc2gc = new Vector(ngcell, 0)
	}




//initiating randm number generator for each pre2post pair
//also randomly select MC to kill "deadMC"

objref rdsynb, rdsyna, rdgc2hc, rdgc2bc, rdgc2mc, rdbc2gc, rdbc2bc, rdbc2mc, deadMC
objref rdmc2gc1, rdmc2gc2, rdmc2bc, rdmc2mc, rdmc2mc1, rdmc2hc, rdhc2gc, rdhc2bc, rdhc2mc, rdgc2gc
ropen("/proc/uptime")		// get a seed  that is changing based on the processing time
	 {			
 	rseed = fscan()		// so simulation will not start with the same seed
	ropen()		
	}
//************************************  GC  ***********************************************
rdgc2bc = new Random(rseed)			// use for syn.connections 
proc new_rdgc2bc() {rdgc2bc.discunif(-1,1)}	// range is based on spread of connections on either side of RING- precell loc =0
new_rdgc2bc()
rdgc2mc = new Random(rseed)			// use for syn.connections 
proc new_rdgc2mc() {rdgc2mc.discunif(0,2)}
new_rdgc2mc()
rdgc2hc = new Random(rseed)			// use for syn.connections 
proc new_rdgc2hc() {rdgc2hc.discunif(-2 , 2)}
new_rdgc2hc()
rdgc2gc = new Random(rseed)			// use for syn.connections 
proc new_rdgc2gc() {rdgc2gc.discunif(-50, 50)}
new_rdgc2gc()

//************************************  BC  ***********************************************
rdbc2gc = new Random(rseed)			// use for syn.connections 
proc new_rdbc2gc() {rdbc2gc.discunif(-70, 70)} // range is based on spread of connections on either side of RING- precell loc =0
new_rdbc2gc()
rdbc2bc = new Random(rseed)			// use for syn.connections 
proc new_rdbc2bc() {rdbc2bc.discunif(-1, 1)}
new_rdbc2bc()
rdbc2mc = new Random(rseed)			// use for syn.connections 
proc new_rdbc2mc() {rdbc2mc.discunif(-3, 3)}
new_rdbc2mc()

//*************************************  MC  ********************************************

//deadMC = new Random(rseed)	//randomly select MC to kill "deadMC" 
//proc new_deadMC() {deadMC.discunif(ngcell+nbcell, ngcell+nbcell+nmcell-1)}
//new_deadMC()
// Check to see if 8 different cells are killed
//for i= 0, 7 {
//MC = deadMC.repick()
//if (killMC.contains(MC) == 0) {
//killMC.x[i] = MC
//} else {i -=1}
//}

rdmc2gc1 = new Random(rseed)			// use for syn.connections 
proc new_rdmc2gc1() {rdmc2gc1.discunif(25, 175)} // range is based on spread of connections on either side of RING- precell loc =0
new_rdmc2gc1()
rdmc2gc2 = new Random(rseed)			// use for syn.connections 
proc new_rdmc2gc2() {rdmc2gc2.discunif(-175, -25)}
new_rdmc2gc2()
rdmc2bc = new Random(rseed)			// use for syn.connections 
proc new_rdmc2bc() {rdmc2bc.discunif(-3,3)}
new_rdmc2bc()
rdmc2mc = new Random(rseed)			// use for syn.connections 
proc new_rdmc2mc() {rdmc2mc.discunif(ngcell+nbcell, ngcell+nbcell+nmcell-1)}
new_rdmc2mc()
rdmc2mc1 = new Random(rseed)			// use for syn.connections 
proc new_rdmc2mc1() {rdmc2mc1.discunif(-3, 3)}
new_rdmc2mc1()
rdmc2hc = new Random(rseed)			// use for syn.connections 
proc new_rdmc2hc() {rdmc2hc.discunif(-2, 2)}
new_rdmc2hc()
//*************************************  HC  ********************************************

rdhc2gc = new Random(rseed)			// use for syn.connections 
proc new_rdhc2gc() {rdhc2gc.discunif(-130, 130)}
new_rdhc2gc()
rdhc2bc = new Random(rseed)			// use for syn.connections 
proc new_rdhc2bc() {rdhc2bc.discunif(-2, 2)}
new_rdhc2bc()
rdhc2mc = new Random(rseed)			// use for syn.connections 
proc new_rdhc2mc() {rdhc2mc.discunif(-2, 2)}
new_rdhc2mc()

//****************  randomizer for the dendritic location of synapse  **************************************

rdsyna = new Random(rseed)		// initialize random distr.
proc new_rdsyna() {rdsyna.discunif(0, 1)} // randomize among 2 dendrites
new_rdsyna()

rdsynb = new Random(rseed)		// initialize random distr.
proc new_rdsynb() {rdsynb.discunif(0, 3)}	// randomize among 4 dendrites
new_rdsynb()

//	NETWORK INITIATION
	for i = 0, ngcell-1 {cell_append(Gcell[i])} // cells 0-499 GCs
	for i = 0, nbcell-1 {cell_append(Bcell[i])} // cells 500-505 BC
	for i = 0, nmcell-1 {cell_append(Mcell[i])} // cells 506-520 MC
	for i = 0, nhcell-1 {cell_append(Hcell[i])} // cells 521-526 HC
	for i = 0, npp-1 {cell_append(PPSt[i])}	// 527 PP artificial cell

//**************Preforant Path  synaptic connections ******************************
proc initNet() { local i,j
for i=0, npp-1 {


		for j=0, 100 {	// to 101 granule cells
	nc_append(i+ngcell+nbcell+nmcell+nhcell, j, 0, 2e-2, 3, 10)  // connect PP to GC[j],syn[0],wt,del,threshold
	nc_append(i+ngcell+nbcell+nmcell+nhcell, j, 1, 2e-2, 3, 1)  // connect PP to GC[j],syn[1],wt,del,threshold 
	}

	for j= ngcell, ngcell+1 { //to 2 BCs
	nc_append(ngcell+nbcell+nmcell+nhcell, j, 0, 1e-2, 3, 10)  // Gcell[3] to Bcell[1]
	nc_append(ngcell+nbcell+nmcell+nhcell, j, 1, 1e-2, 3, 10)  // Gcell[3] to Bcell[1]
	}

//	for j=0, 1 { 	// 15% of MCs have OML dendrites so 2 of 15 MCs could get PP input
//	 npost = rdmc2mc.repick() //pick MC at random
//	dbr = rdsynb.repick()
// if the MC is not already connected to PP and the randomly picked MC is proximal to the stimulated GCs
//	if ((is_connected(MossyCell[npost-ngcell-nbcell], PPstim[0]) == 0) && (npost < ngcell+nbcell+3) && (killMC.contains(npost) == 0)) {
//connect PP syn to the selected mossy
//	nc_append(ngcell+nbcell+nmcell+nhcell, npost, dbr, 0.5e-2, 3, 10)  // Gcell[3] to Bcell[1]
//	print npost, dbr
//	} else {	j -= 1	print "pp2mc"}
//	if (killMC.contains(npost) == 1) {j +=1}
//	}

}
//******************************************************************************************

//**************Granule Cell post synaptic connections ******************************


for  i=0, ngcell-1 {

	for j=0, 0 {
// Based on the lamellar distribution of the GCs to BCs - 500 GCs were divided into 6 groups proximal to each of the 6 BCs
	if (i < 84) { a=0}
	if ((i > 83) && (i < 166)) { a=1}
	if ((i > 165) && (i < 252)) { a=2}
	if ((i > 251) && (i < 336)) { a=3}
	if ((i > 335) && (i < 420)) { a=4}
	if ((i > 419) && (i < 500)) { a=5}

	 Gauz3 = rdgc2bc.repick() // randomly pick location of post synaptic Bcell
	if (a+Gauz3 > 5) {npost = a+Gauz3-6 } //determine appropriate post syn BC
	if (a+Gauz3 < 0) {npost = a+Gauz3+6} 
	if ((a+Gauz3 > -1) && (a+Gauz3 < 6)) {npost = a+Gauz3}
	dbr = rdsynb.repick() // randomly pick the dendrite to connect to
	print npost, a
	if (vgc2bc.x[npost] < 90)  { //check to make sure that post syn BC does not get more than 90 GC synapses
	nc_append(i, ngcell+npost, dbr+2, 4.7e-3, .8, 10)  // connect GC[i] to BC[j],syn[2]+dendritic_var,wt,del,threshold
	print i, npost, dbr+2
	vgc2bc.x[npost]  +=1 //increment the no of synapses to the post cell
	} else {j -= 1	print "nogc2bc"} // for connection that is not made reconnect axon to another cell
	}
// Based on the lamellar distribution of the GCs to MCs - 500 GCs were divided into 5 groups, 3 MCs were distributed in each lamella
	for j=0, 0 {
	if (i < 100) { a=0}
	if ((i > 99) && (i < 200)) { a=1}
	if ((i > 199) && (i < 300)) { a=2}
	if ((i > 299) && (i < 400)) { a=3}
	if ((i > 399) && (i < 500)) { a=4}
	b=a*3
	 npost = rdgc2mc.repick()
	dbr = rdsynb.repick()
//	print npost, b
//	if ((vgc2mc.x[npost+b] < 38) && (killMC.contains(ngcell+nbcell+npost+b) == 0)){ // use if killing MC
	if (vgc2mc.x[npost+b] < 38){
	nc_append(i, ngcell+nbcell+npost+b, dbr+4, 0.2e-3, 1.5, 10)  // Gcell[3] to Bcell[1]
//	print npost+b, dbr+4
	vgc2mc.x[npost+b] +=1
	} else {	j -= 1	print "nogc2mc"}
//	if (killMC.contains(ngcell+nbcell+npost+b) == 1) {j +=1 print "dead MC"}	// use if killing MC
	}

	for j=0, 2 {
	if (i < 84) { a=0}
	if ((i > 83) && (i < 166)) { a=1}
	if ((i > 165) && (i < 252)) { a=2}
	if ((i > 251) && (i < 336)) { a=3}
	if ((i > 335) && (i < 420)) { a=4}
	if ((i > 419) && (i < 500)) { a=5}
	 Gauz3 = rdgc2hc.repick()
	if (a+Gauz3 > 5) {npost = a+Gauz3-6 }
	if (a+Gauz3 < 0) {npost = a+Gauz3+6} 
	if ((a+Gauz3 > -1) && (a+Gauz3 < 6)) {npost = a+Gauz3}
	dbr = rdsynb.repick()
	if ((is_connected(HIPPCell[npost], GranuleCell[i]) == 0) && (vgc2hc.x[npost] < 275)) {
	nc_append(i, ngcell+nbcell+nmcell+npost, dbr, 0.5e-3, 1.5, 10)  // Gcell[3] to Bcell[1]
//	print npost, dbr
	vgc2hc.x[npost] +=1
	} else {j -= 1	print "hhhh"}
	}
// NOTE: THIS IS FOR SPROUTED SYNAPSES
	for j=0, 9 {
	 Gauz3 = rdgc2gc.repick()
	//print Gauz3
	if (i+Gauz3 > 499) {npost = i+Gauz3-500 }
	if (i+Gauz3 < 0) {npost = i+Gauz3+500} 
	if ((i+Gauz3 > -1) && (i+Gauz3 < 500)) {npost = i+Gauz3}
	//print npost
	dbr = rdsyna.repick()
	if ((is_connected(GranuleCell[npost], GranuleCell[i]) == 0) && (vgc2gc.x[npost] < 15)) {
	nc_append(i, npost, dbr+7, 2e-3, .8, 10)  // Gcell[3] to Bcell[1]
	//	print npost, dbr+8
	vgc2gc.x[npost] +=1
	} else {j -= 1	print "gc2gc"}
	}
}
//******************************************************************************************

//**************Basket Cell post synaptic connections ******************************



for  i=0, nbcell-1 {
	
		for j=0, 99 {
	 Gauz3 = rdbc2gc.repick()
print Gauz3
	if (i*83+41+Gauz3 > 499) {npost = i*83+41+Gauz3-500 }
	if (i*83+41+Gauz3 < 0) {npost = i*83+41+Gauz3+500} 
	if ((i*83+41+Gauz3 > -1) && (i*83+41+Gauz3 < 500)) {npost = i*83+41+Gauz3}
print i, npost
	if ((is_connected(GranuleCell[npost], BasketCell[i]) == 0) && (vbc2gc.x[npost] < 2)) {
	nc_append(i+ngcell, npost, 6, 1.6e-3, .85, -10)  // Gcell[3] to Bcell[1]
	vbc2gc.x[npost] +=1
	print i, npost, 6
	} else {j -= 1	print "BC2GC"}
	}

	for j=0, 1 {
	 Gauz3  = rdbc2bc.repick()
//print Gauz3
	if (i+Gauz3 > 5) {npost = i+Gauz3-6 }
	if (i+Gauz3 < 0) {npost = i+Gauz3+6} 
	if ((i+Gauz3 >-1) && (i+Gauz3 < 6)) {npost = i+Gauz3}
	dbr = rdsyna.repick()
	if ((is_connected(BasketCell[npost], BasketCell[i]) == 0) && (vbc2bc.x[npost] < 3)) {
	nc_append(i+ngcell, npost+ngcell, dbr+8, 7.6e-3, .8, -10)  // Gcell[3] to Bcell[1]
	print npost, dbr+8
	vbc2bc.x[npost] +=1
	} else {j -= 1	print "bc2bc"}
	}

	for j=0, 2 {
	 Gauz3 = rdbc2mc.repick()
//print Gauz3
	if (i*2+2+Gauz3 > 14) {npost = i*2+2+Gauz3-15 }
	if (i*2+2+Gauz3 < 0) {npost = i*2+2+Gauz3+15} 
	if ((i*2+2+Gauz3 >-1) && (i*2+2+Gauz3 < 15)) {npost = i*2+2+Gauz3}
//print npost	 
//	if ((is_connected(MossyCell[npost], BasketCell[i]) == 0) && (vbc2mc.x[npost] < 3) && (killMC.contains(ngcell+nbcell+npost) == 0)) {	// use if killing MC
	if ((is_connected(MossyCell[npost], BasketCell[i]) == 0) && (vbc2mc.x[npost] < 3)) {
	nc_append(i+ngcell, npost+ngcell+nbcell, 12, 1.5e-3, 1.5, -10)  // Gcell[3] to Bcell[1]
	print npost, 12
	vbc2mc.x[npost] +=1
	} else {	j -= 1	print "bc2mc"}
//	if (killMC.contains(ngcell+nbcell+npost) == 1) {j +=1 print "dead MC"}	// use if killing MC
	}


}
//******************************************************************************************

//**************Mossy Cell post synaptic connections ******************************



for  i=0, nmcell-1 {
//if (killMC.contains(ngcell+nbcell+i) == 0){ 	// use if killing MC

	if (i < 3) { y=0}
	if ((i > 2) && (i < 6)) { y=1}
	if ((i > 5) && (i < 9)) { y=2}
	if ((i > 8) && (i < 12)) { y=3}
	if ((i > 11) && (i < 15)) { y=4}
	
		for j=0, 99 {
	 Gauz1 = rdmc2gc1.repick()
print Gauz1
	if (i*33+17+Gauz1 > 499) {
	 npost1 = i*33+17+Gauz1-500
	} else {npost1 =i*33+17+Gauz1}
print npost1
	dbr = rdsyna.repick()
	if ((is_connected(GranuleCell[npost1], MossyCell[i]) == 0) && (vmc2gc.x[npost1] < 7))  {
	nc_append(i+ngcell+nbcell, npost1, dbr+2, 0.3e-3, 3, 10)  // Gcell[3] to Bcell[1]
	vmc2gc.x[npost1] +=1
	print i, npost1, dbr+2
	} else {j -= 1	print "MC2GC1"}
	}
		for j=0, 99 {
	 Gauz2 = rdmc2gc2.repick()
//print Gauz2
	if (i*33+17+Gauz2 < 0) {
	 npost2 =i*33+17+Gauz2+500
	} else {npost2 =i*33+17+Gauz2}
//print npost2
	dbr = rdsyna.repick()
	if ((is_connected(GranuleCell[npost2], MossyCell[i]) == 0) && (vmc2gc.x[npost2] < 7))  {
	nc_append(i+ngcell+nbcell, npost2, dbr+2, 0.3e-3, 3, 10)  // Gcell[3] to Bcell[1]
	vmc2gc.x[npost2] +=1
//	print i, npost2, dbr+2
	} else {j -= 1	print "MC2GC2"}
	}

	for j=0, 0 {
	 Gauz3 = rdmc2bc.repick()
	if (y+Gauz3 > 5) {npost = y+Gauz3-6}
	if (y+Gauz3 < 0) {npost = y+Gauz3+6} 
	if ((y+Gauz3 > -1) && (y+Gauz3 < 6)) {npost = y+Gauz3}
	dbr = rdsyna.repick()
	if ((vmc2bc.x[npost] < 4) && (Gauz3 !=0)) {
	nc_append(i+ngcell+nbcell, ngcell+npost, dbr+6, 0.3e-3, 3, 10)  // Gcell[3] to Bcell[1]
//	print npost, dbr+6
	vmc2bc.x[npost] += 1
	} else {j -= 1	print "mc2bc"}
	}

	for j=0, 2 {
	 Gauz3 = rdmc2mc1.repick()
//print Gauz3
	if (i+Gauz3 > 14) {npost = i+Gauz3-15 }
	if (i+Gauz3 < 0) {npost = i+Gauz3+15} 
	if ((i+Gauz3 >-1) && (i+Gauz3 < 15)) {npost = i+Gauz3}
//print npost
	dbr = rdsynb.repick()
//	if ((is_connected(MossyCell[npost], MossyCell[i]) == 0) && (vmc2mc.x[npost] < 4) && (Gauz3 != 0) && (killMC.contains(ngcell+nbcell+npost) == 0))  {	// use if killing MC
	if ((is_connected(MossyCell[npost], MossyCell[i]) == 0) && (vmc2mc.x[npost] < 4) && (Gauz3 != 0))  {
	nc_append(i+ngcell+nbcell, npost+ngcell+nbcell, dbr+8, 0.5e-3, 2, 10)  // Gcell[3] to Bcell[1]
//	print npost, dbr+8
	vmc2mc.x[npost] +=1
	} else {	j -= 1	print "mc2mc"}
// 	if (killMC.contains(ngcell+nbcell+npost) == 1){ j += 1 print "dead MC"}	// use if killing MC
	}

	for j=0, 1 {
	 Gauz3 = rdmc2hc.repick()
	if (y+Gauz3 > 5) {npost = y+Gauz3-6}
	if (y+Gauz3 < 0) {npost = y+Gauz3+6} 
	if ((y+Gauz3 > -1) && (y+Gauz3 < 6)) {npost = y+Gauz3}
	dbr = rdsynb.repick()
	if ((is_connected(HIPPCell[npost], MossyCell[i]) == 0) && (vmc2hc.x[npost] < 7) && (Gauz3 != 0))  {
	nc_append(i+ngcell+nbcell, ngcell+nbcell+nmcell+npost, dbr+4, 0.2e-3, 3, 10)  // Gcell[3] to Bcell[1]
//	print npost, dbr+4
	vmc2hc.x[npost] +=1
	} else {	j -= 1	print y, Gauz3, "mc2hc"}
	}

//}
}
//******************************************************************************************
//**************HIPP Cell post synaptic connections ******************************



 for  i=0, nhcell-1 {
	
		for j=0, 159 {
	 Gauz3 = rdhc2gc.repick()
//print Gauz3
	if (i*83+41+Gauz3 > 499) {npost = i*83+41+Gauz3-500 }
	if (i*83+41+Gauz3 < 0) {npost = i*83+41+Gauz3+500} 
	if ((i*83+41+Gauz3 > -1) && (i*83+41+Gauz3 < 500)) {npost = i*83+41+Gauz3}
//print npost
	dbr = rdsyna.repick()
	if ((is_connected(GranuleCell[npost], HIPPCell[i]) == 0) && (vhc2gc.x[npost] < 3))  {
	nc_append(i+ngcell+nbcell+nmcell, npost, dbr+4, 0.5e-3, 1.6, 10)  // Gcell[3] to Bcell[1]
	vhc2gc.x[npost] +=1
	print i, npost, dbr+4
	} else {j -= 1	print "HC2GC"}
	}

	for j=0, 3 {
	  Gauz3 = rdhc2bc.repick()
	if (i+Gauz3 > 5) {npost = i+Gauz3-6}
	if (i+Gauz3 < 0) {npost = i+Gauz3+6} 
	if ((i+Gauz3 > -1) && (i+Gauz3 < 6)) {npost = i+Gauz3}
	dbr = rdsyna.repick()
	if ((is_connected(BasketCell[npost], HIPPCell[i]) == 0) && (vhc2bc.x[npost] < 5))  {
	nc_append(i+ngcell+nbcell+nmcell, npost+ngcell, dbr+10, 0.5e-3, 1.6, 10)  // Gcell[3] to Bcell[1]
	print npost, dbr+10
	vhc2bc.x[npost] += 1
	} else {j -= 1	print "hc2bc"}
	}

	for j=0, 3 {
	 Gauz3 = rdhc2mc.repick()
//print Gauz3
	if (i*2+2+Gauz3 > 14) {npost = i*2+2+Gauz3-15 }
	if (i*2+2+Gauz3 < 0) {npost = i*2+2+Gauz3+15} 
	if ((i*2+2+Gauz3 >-1) && (i*2+2+Gauz3 < 15)) {npost = i*2+2+Gauz3}
//print npost
	dbr = rdsynb.repick()
//	if ((is_connected(MossyCell[npost], HIPPCell[i]) == 0) && (vhc2mc.x[npost] < 2) && (killMC.contains(ngcell+nbcell+npost) == 0))  {	//use if killing MC
	if ((is_connected(MossyCell[npost], HIPPCell[i]) == 0) && (vhc2mc.x[npost] < 2))  {
	nc_append(i+ngcell+nbcell+nmcell, npost+ngcell+nbcell, dbr+13, 1.5e-3, 1, 10)  // Gcell[3] to Bcell[1]
	print npost, dbr+13
	vhc2mc.x[npost] += 1
	} else {	j -= 1	print "hc2mc"}
// 	if (killMC.contains(ngcell+nbcell+npost) == 1){ j += 1 print "dead MC"} //use if killing MC
	}

}

}
//*********************************Print out Net cons*********************************************************
strdef strvar
objref dfile
dfile = new File()

proc saveNet(){ local i
	dfile.wopen("DGNC.txt")
	dfile.printf("Precell \tpstcell \t Synapse \n")
	for i=0, nclist.count-1 {
	dfile.printf("%s\t%s\t%s\n", nclist.object[i].precell, nclist.object[i].postcell, nclist.object[i].syn)}

dfile.printf("TO BC\n GC \tBC \tMC \tHC \n")
for i= 0, nbcell-1 {dfile.printf("%d\t%d\t%d\t%d \n",  vgc2bc.x[i], vbc2bc.x[i], vmc2bc.x[i], vhc2bc.x[i])}
dfile.printf("TO MC\n GC \tBC \tMC \tHC \n")
for i= 0, nmcell-1 {dfile.printf("%d\t%d\t%d\t%d\n",  vgc2mc.x[i], vbc2mc.x[i], vmc2mc.x[i], vhc2mc.x[i])}
dfile.printf("TO HC \n GC\t MC\n")
for i= 0, nhcell-1 {dfile.printf("%d\t%d\n", vgc2hc.x[i], vmc2hc.x[i])}
dfile.printf("TO GC\n BC\t MC\t HC\t GC\n")
for i= 0, ngcell-1 {dfile.printf("%d\t%d\t%d\t%d\n", vbc2gc.x[i], vmc2gc.x[i], vhc2gc.x[i], vgc2gc.x[i])}
dfile.close()

}


//*******  output memb voltage traces of every 10th GC and all other cells to file **********************************************
strdef strmat
objref efile
efile = new File()

	efile.wopen("DGVt.txt")
	efile.printf("t\t")
	for i = 0, 49 {
	b = i*10
	efile.printf("%s\t", cells.object[b])}
	for i = 498, cells.count-2{
	efile.printf("%s\t", cells.object[i])}
	efile.printf("\n")
	efile.close("DGVt.txt")

proc sMatrix(){ local  j

	efile.aopen("DGVt.txt")
	efile.printf("%f\t", t)
	for i = 0, 49 {
	b = i*10
	efile.printf("%f\t", cells.object[b].soma.v(0.5))}
	for j =498, cells.count-2 {
	efile.printf("%f\t", cells.object[j].soma.v(0.5))}
	efile.printf("\n")
	efile.close("DGVt.txt")
}

objref  VmT
objref VmMat[cells.count-1]
VmT = new Vector()
for i=0, cells.count-2 {
	VmMat[i] = new Vector()
	}

proc VecMx() { local i
	VmT.append(t)
	for i=0, cells.count-2 {
		VmMat[i].append( cells.object[i].soma.v(0.5))
		}
	}
//Generate spike matrix and save to file	
objref Spike[cells.count-1]
for i=0, cells.count-2 {
	Spike[i] = new Vector()
	}
strdef Spkstr
objref dfile
dfile = new File()


proc SpkMx() { local i, j
	for i=0, cells.count-2 {
		Spike[i].spikebin(VmMat[i], 0)
		}

	dfile.wopen("DGSp.txt")

	while(k <  VmT.size) {
	for j = 0, cells.count-2 {
	if(Spike[j].x[k] != 0) {
	dfile.printf("%f\t%d\n", VmT.x[k], j)}
	}
	k +=1 }
	dfile.close("DGSp.txt")
	}


objref r_plt
proc initrPlt() {
	r_plt = new Graph(0)
	r_plt.size(0, tstop,0, cells.count)
	r_plt.label(0.95, 0.02, "ms")
	r_plt.label(0.01, 0.82, "neu")
	r_plt.view(0,0, tstop, cells.count,320,20,300,230)
}
 initrPlt()
//Plot spike raster
proc plotAP() { local i, a
	a=1
 	r_plt.erase()
	while(j < cells.count-2) {
	for i = 0, VmT.size-1 {
	if ((j > ngcell-1)&&(j < ngcell+nbcell-1)) { a=2}
	if ((j > ngcell+nbcell-1)&&(j < ngcell+nbcell+nmcell-1)) { a=3}
	if (j > ngcell+nbcell+nmcell-1) { a=4}
	if (Spike[j].x[i] == 1) {
	r_plt.mark(VmT.x[i], j, "T", 5, a, 1)}}
	j+=1}
	r_plt.flush()
	}


//################################################################################################
proc init() { local dtsav, temp, secsav
finitialize(v_init)
t = -1000 // negative t step to initialize to steady state
dtsav = dt
secondorder =0
dt= 10
	// if cvode is on, turn it off to do large fixed step
temp= cvode.active()
if (temp!=0) {cvode.active(0)}
while(t<-100) { fadvance() print t}
	//restore cvode if reqd
if (temp!=0) {cvode.active(1)}
dt = dtsav
secondorder =2
t = 0
if (cvode.active()){
cvode.re_init()
}else{
fcurrent()
}
//frecord_init()
}
proc continuerun() {local rt
	eventcount =0
	eventslow =1
	stoprun =0
	if (using_cvode_) {
	cvode.event($1)
	}
	while(t < $1 && stoprun == 0) {
	step()
	sMatrix() 
	VecMx()
	rt = stopsw()
	if (rt > realtime) {
		realtime = rt
		if (!stdrun_quiet) fastflushPlot()
		doNotify()
		if (realtime == 2 && eventcount > 50) {
			eventslow = int(eventcount/50)+1
		}
		eventcount = 0
	}else{
		eventcount = eventcount +1
		if ((eventcount%eventslow) == 0) {
			doEvents()
		}
	}
	}
	flushPlot()
}

objectvar save_window_, rvp_
objectvar scene_vector_[4]
objectvar ocbox_, ocbox_list_, scene_, scene_list_
{ocbox_list_ = new List()  scene_list_ = new List()}

{
xpanel("RunControl", 0)
v_init = -60
xvalue("Init","v_init", 1,"stdinit()", 1, 1 )
xbutton("Init & Run","run()")
xbutton("Stop","stoprun=1")
runStopAt = 5
xvalue("Continue til","runStopAt", 1,"{continuerun(runStopAt) stoprun=1}", 1, 1 )
runStopIn = 1
xvalue("Continue for","runStopIn", 1,"{continuerun(t + runStopIn) stoprun=1}", 1, 1 )
xbutton("Single Step","steprun()")
t = 0
xvalue("t","t", 2 )
tstop = 300	//1500
xvalue("Tstop","tstop", 1,"tstop_changed()", 0, 1 )
dt = 0.1
xvalue("dt","dt", 1,"setdt()", 0, 1 )
steps_per_ms = 10	//40
xvalue("Points plotted/ms","steps_per_ms", 1,"setdt()", 0, 1 )
xpanel(544,121)
}

//plot membrane voltage traces
{
save_window_ = new Graph(0)
save_window_.size(0,tstop,-80,40)
scene_vector_[2] = save_window_
{save_window_.view(0, -80, tstop, 120, 290, 470, 579.84, 208)}
graphList[0].append(save_window_)
save_window_.save_name("graphList[0].")
save_window_.addexpr("Gcell[0].soma.v(0.5)",1,1)
save_window_.addexpr("Bcell[0].soma.v(0.5)",2,1)
save_window_.addexpr("Bcell[1].soma.v(0.5)",5,1)
save_window_.addexpr("Mcell[0].soma.v(0.5)",3,1)
save_window_.addexpr("Hcell[0].soma.v(0.5)",4,1)
}


proc rrun(){
initNet()
saveNet()
run()
SpkMx()
}

rrun()
plotAP()

objectvar scene_vector_[1]
{doNotify()}
//quit()

Loading data, please wait...