Spine head calcium in a CA1 pyramidal cell model (Graham et al. 2014)

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Accession:154732
"We use a computational model of a hippocampal CA1 pyramidal cell to demonstrate that spine head calcium provides an instantaneous readout at each synapse of the postsynaptic weighted sum of all presynaptic activity impinging on the cell. The form of the readout is equivalent to the functions of weighted, summed inputs used in neural network learning rules. Within a dendritic layer, peak spine head calcium levels are either a linear or sigmoidal function of the number of coactive synapses, with nonlinearity depending on the ability of voltage spread in the dendrites to reach calcium spike threshold. ..."
Reference:
1 . Graham BP, Saudargiene A, Cobb S (2014) Spine head calcium as a measure of summed postsynaptic activity for driving synaptic plasticity. Neural Comput 26:2194-222 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism: Hippocampus;
Cell Type(s):
Channel(s):
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Synaptic Integration;
Implementer(s): Graham, Bruce [B.Graham at cs.stir.ac.uk];
/
GrahamEtAl2014
Cells
Results
readme.html
burststim2.mod *
cad.mod
cagk.mod
carF.mod
distca.mod
distr.mod *
h.mod *
kadist.mod *
kaprox.mod *
kca.mod *
kdrca1.mod *
km.mod
na3n.mod *
naxn.mod *
nmdaca.mod *
burst_cell.hoc *
CA1PC.hoc
mosinit.hoc
randomlocation.hoc
ranstream.hoc *
run_batsyn.hoc
run_PC.hoc
screenshot1.png
screenshot2.png
screenshot3.png
setup_PC.hoc
synstim.ses
                            
// Setting synaptic stimuli to cell model
// Stimuli are single synchronous spikes to a set of input synapses
// (more complicated stimuli, such as bursts, with repetitions, are possible)
// Last update: BPG 2-5-14

// number of synaptic contacts (initial values setting in calling file)
nCA3max = nCA3 	// apical
nCA3bmax = nCA3b 	// basal
nECmax = nEC
nBCmax = nBC
nBSCmax = nBSC

// PC synapse types
AMPA = 1
AMNM = 2	// AMPA/NMDA
GABAA = 3
GABAB = 4
flag_spines = 1	// set to 1 if SR spines required
flag_ECspines = 1 // set to 1 if spines required in SLM
tot_spines = 0
if (flag_spines == 1) tot_spines = nCA3+nCA3b
if (flag_ECspines == 1) tot_spines = tot_spines+nEC
flag_ECbranch = 0	// set to 1 if EC synapses on single branch
flag_SRbranch = 0	// set>0 if SR synapses on single branch: 1=proximal, 2=distal

soma_caR = 0.03 
soma_sAHP = 0.001
soma_mAHP = 0.001
caR_init = 0.03 
sAHP_init = 0.001
mAHP_init = 0.001
caR_spine = 0.03 
sAHP_spine = 0.001
mAHP_spine = 0.001

STARTDEL = 50	// msecs
THETA = 200	// msecs (5 Hz)
GAMMA = 10	// msecs (100 Hz)
ECCA3DEL = 0	// msecs
SIMDUR = STARTDEL + (THETA*5)	// simulation duration (msecs)

// EC (PP) excitation
ECNUM = 100	// number of EC spikes
ECSTART = STARTDEL	// time of first EC spike
ECNOISE = 0	// EC ISI noise
ECINT = 1000	// EC spike ISI (one spike for simulation period)
ECBINT = 1000	// EC burst interval
ECBLEN = 10	// EC burst length
//ECINT = GAMMA	// EC spike ISI
//ECBINT = THETA	// EC burst interval
//ECBLEN = GAMMA*5	// EC burst length
ECWGT = 0.0001	// EC weight to PCs (AMPA)
ECNWGT = 0.0008	// EC weight to PCs (NMDA)
ECDEL = 1	// EC delay

// SC (SR) excitation
CNUM = 100	// number of cue spikes
CSTART = STARTDEL+ECCA3DEL	// time of first cue spike
CNOISE = 0	// cue ISI noise
CINT = 1000	// EC spike ISI (one spike for simulation period)
CBINT = 1000	// EC burst interval
CBLEN = 10	// EC burst length
//CINT = GAMMA	// cue spike ISI
//CBINT = THETA	// EC burst interval
//CBLEN = GAMMA*5	// EC burst length
CAWGT = 0.0005	// cue weight (AMPA)
CNWGT = 0.001	// excitatory weights (NMDA)
CAWGTb = 0.0005	// cue weight (basal AMPA)
CNWGTb = 0.001	// excitatory weights (basal NMDA)
CDEL = 1	// cue delay

// BC inhibition
BCNUM = 100	// number of BC spikes
BCSTART = STARTDEL+1000	// time of first cue spike
BCINT = GAMMA	// BC spike ISI
BCNOISE = 0.05	// BC ISI noise
BCBINT = THETA-(GAMMA*5)	// BC burst interval
BCBLEN = THETA*10	// BC burst length (continuous inhib)
//BCBLEN = GAMMA*10	// BC burst length
BCWGT = 0.0    // BC weight (GABAA)
BCDEL = 3	// BC delay

// BSC inhibition
BSCNUM = 100	// number of BC spikes
BSCSTART = STARTDEL+1000	// time of first cue spike
BSCINT = GAMMA	// BC spike ISI
BSCNOISE = 0.05	// BC ISI noise
BSCBINT = THETA-(GAMMA*5)	// BC burst interval
BSCBLEN = THETA*10	// BC burst length (continuous inhib)
//BSCBLEN = GAMMA*10	// BC burst length
BSCWGT = 0.0    // BC weight (GABAA)
BSCDEL = 3	// BC delay


{load_file("ranstream.hoc")}  // to give each cell its own sequence generator
{load_file("randomlocation.hoc")}
{load_file("CA1PC.hoc")}
//{load_file("stim_cell.hoc")}
{load_file("burst_cell.hoc")}

objref cell
objref CA3list, EClist, BClist, BSClist
objref ncCA3list, ncCA3Nlist, ncEClist, ncECNlist, ncBClist, ncBSClist

mcell_ran4_init(connect_random_low_start_)

cell = new PyramidalCell()

access cell.soma
print "Segments: ", cell.totnseg, "; Area: ", cell.totarea

objref rs, nil
rs = new RandomStream(my_seed)
rs.start()

proc makeCA3() {local i
  if (flag_SRbranch == 0) {
    cell.newsyn(AMNM, nCA3, cell.SR_list, rs.r, flag_spines, tot_spines)	// CA3 AMPA/NMDA synapses in SR
  } else {
    if (flag_SRbranch == 1) {	// proximal branch
      cell.newsyn(AMNM, nCA3, cell.SRbrp_list, rs.r, flag_spines, tot_spines)	// CA3 AMPA/NMDA synapses in SR
    } else if (flag_SRbranch == 2) {  // distal branch
      cell.newsyn(AMNM, nCA3, cell.SRbrd_list, rs.r, flag_spines, tot_spines)	// CA3 AMPA/NMDA synapses in SR    
    } else if (flag_SRbranch == 3) {  // all proximal
      cell.newsyn(AMNM, nCA3, cell.SRprox_list, rs.r, flag_spines, tot_spines)	// CA3 AMPA/NMDA synapses in SR    
    } else if (flag_SRbranch == 4) {  // all distal
      cell.newsyn(AMNM, nCA3, cell.SRdist_list, rs.r, flag_spines, tot_spines)	// CA3 AMPA/NMDA synapses in SR    
    } else if (flag_SRbranch == 5) {  // trunk 1
      cell.newsyn(AMNM, nCA3, cell.SRbrt_list, rs.r, flag_spines, tot_spines)	// CA3 AMPA/NMDA synapses in SR    
    } else if (flag_SRbranch == 6) {  // trunk 2
      cell.newsyn(AMNM, nCA3, cell.SRbrt2_list, rs.r, flag_spines, tot_spines)	// CA3 AMPA/NMDA synapses in SR    
    } else {  // trunk combined
      cell.newsyn(AMNM, nCA3, cell.SRbrtc_list, rs.r, flag_spines, tot_spines)	// CA3 AMPA/NMDA synapses in SR    
    }
  }
  CA3list = new List()
  ncCA3list = new List()	// AMPA synapses
  ncCA3Nlist = new List()	// NMDA synapses
  for (i=0; i < nCA3; i=i+1) {
    CA3list.append(new BurstCell())
    CA3list.o(i).connect2target(nil)  // attach spike detector to cell
    ncCA3list.append(new NetCon(CA3list.o(i).stim, cell.pre_list.o(2*i)))
    ncCA3Nlist.append(new NetCon(CA3list.o(i).stim, cell.pre_list.o(2*i+1)))
    CA3list.o(i).stim.number = CNUM
    CA3list.o(i).stim.start = CSTART
    CA3list.o(i).stim.interval = CINT
    CA3list.o(i).stim.noise = CNOISE
    CA3list.o(i).stim.burstint = CBINT
    CA3list.o(i).stim.burstlen = CBLEN
    ncCA3list.o(i).weight = CAWGT	
    ncCA3list.o(i).delay = CDEL
    ncCA3Nlist.o(i).weight = CNWGT	
    ncCA3Nlist.o(i).delay = CDEL
  }
}

// NOTE: must be created after CA3 SR inputs
proc makeCA3b() {local i
  cell.newsyn(AMNM, nCA3b, cell.basal_list, rs.r, flag_spines, tot_spines) // CA3 AMPA/NMDA synapses in SO
  for (i=nCA3; i < nCA3+nCA3b; i=i+1) {
    CA3list.append(new BurstCell())
    CA3list.o(i).connect2target(nil)  // attach spike detector to cell
    ncCA3list.append(new NetCon(CA3list.o(i).stim, cell.pre_list.o(2*i)))
    ncCA3Nlist.append(new NetCon(CA3list.o(i).stim, cell.pre_list.o(2*i+1)))
    CA3list.o(i).stim.number = CNUM
    CA3list.o(i).stim.start = CSTART
    CA3list.o(i).stim.interval = CINT
    CA3list.o(i).stim.noise = CNOISE
    CA3list.o(i).stim.burstint = CBINT
    CA3list.o(i).stim.burstlen = CBLEN
    ncCA3list.o(i).weight = CAWGTb	
    ncCA3list.o(i).delay = CDEL
    ncCA3Nlist.o(i).weight = CNWGTb	
    ncCA3Nlist.o(i).delay = CDEL
  }
}

// NOTE: synapse indexing on basis that CA3 AMPA/NMDA synapses created first
proc makeEC() {local i
  if (flag_ECbranch == 0) {
    cell.newsyn(AMNM, nEC, cell.SLM_list, rs.r, flag_ECspines, tot_spines)	// EC AMPA/NMDA synapses in SLM
  } else if (flag_ECbranch == 1) {	// one branch
    cell.newsyn(AMNM, nEC, cell.SLMbr_list, rs.r, flag_ECspines, tot_spines)	// EC AMPA/NMDA synapses in SLM
  } else {	// trunk group
    cell.newsyn(AMNM, nEC, cell.SLMbrt_list, rs.r, flag_ECspines, tot_spines)	// EC AMPA/NMDA synapses in SLM
  }
  EClist = new List()
  ncEClist = new List()
  ncECNlist = new List()
  for (i=0; i < nEC; i=i+1) {
    EClist.append(new BurstCell())
    EClist.o(i).connect2target(nil)  // attach spike detector to cell
    ncEClist.append(new NetCon(EClist.o(i).stim, cell.pre_list.o(2*i+2*(nCA3+nCA3b))))
    ncECNlist.append(new NetCon(EClist.o(i).stim, cell.pre_list.o(2*i+2*(nCA3+nCA3b)+1)))
    EClist.o(i).stim.number = ECNUM
    EClist.o(i).stim.start = ECSTART
    EClist.o(i).stim.interval = ECINT
    EClist.o(i).stim.noise = ECNOISE
    EClist.o(i).stim.burstint = ECBINT
    EClist.o(i).stim.burstlen = ECBLEN
    ncEClist.o(i).weight = ECWGT	
    ncEClist.o(i).delay = ECDEL
    ncECNlist.o(i).weight = ECNWGT	
    ncECNlist.o(i).delay = ECDEL
  }
}

// NOTE: synapse indexing on basis that CA3/EC AMPA/NMDA synapses created first
proc makeBC() {local i
  cell.newsyn(GABAA, nBC, cell.soma_list, rs.r, 0, 0)	// BC GABAA synapses in soma
  BClist = new List()
  ncBClist = new List()
  for (i=0; i < nBC; i=i+1) {
    BClist.append(new BurstCell())
    BClist.o(i).connect2target(nil)  // attach spike detector to cell
    ncBClist.append(new NetCon(BClist.o(i).stim, cell.pre_list.o(i+2*(nCA3+nCA3b+nEC))))
    BClist.o(i).stim.number = BCNUM
    BClist.o(i).stim.start = BCSTART
    BClist.o(i).stim.interval = BCINT
    BClist.o(i).stim.noise = BCNOISE
    BClist.o(i).stim.burstint = BCBINT
    BClist.o(i).stim.burstlen = BCBLEN
    ncBClist.o(i).weight = BCWGT	
    ncBClist.o(i).delay = BCDEL
  }
}

// NOTE: synapse indexing on basis that CA3/EC AMPA/NMDA synapses created first
proc makeBSC() {local i
  cell.newsyn(GABAA, nBSC, cell.SR_list, rs.r, 0, 0)	// BSC GABAA synapses in SR
  BSClist = new List()
  ncBSClist = new List()
  for (i=0; i < nBC; i=i+1) {
    BSClist.append(new BurstCell())
    BSClist.o(i).connect2target(nil)  // attach spike detector to cell
    ncBSClist.append(new NetCon(BSClist.o(i).stim, cell.pre_list.o(i+2*(nCA3+nCA3b+nEC)+nBC)))
    BSClist.o(i).stim.number = BSCNUM
    BSClist.o(i).stim.start = BSCSTART
    BSClist.o(i).stim.interval = BSCINT
    BSClist.o(i).stim.noise = BSCNOISE
    BSClist.o(i).stim.burstint = BSCBINT
    BSClist.o(i).stim.burstlen = BSCBLEN
    ncBSClist.o(i).weight = BSCWGT	
    ncBSClist.o(i).delay = BSCDEL
  }
}

proc setCA3() {local i
  for (i=0; i < nCA3; i=i+1) {
    CA3list.o(i).stim.number = CNUM
    CA3list.o(i).stim.start = CSTART
    CA3list.o(i).stim.interval = CINT
    CA3list.o(i).stim.noise = CNOISE
    CA3list.o(i).stim.burstint = CBINT
    CA3list.o(i).stim.burstlen = CBLEN
    ncCA3list.o(i).weight = CAWGT	
    ncCA3list.o(i).delay = CDEL
    ncCA3Nlist.o(i).weight = CNWGT	
    ncCA3Nlist.o(i).delay = CDEL
  }
  // silence any extra synapses
  for (i=nCA3; i < nCA3max; i=i+1) {
    CA3list.o(i).stim.number = 0
    ncCA3list.o(i).weight = 0	
    ncCA3Nlist.o(i).weight = 0	
  }
}

proc setCA3b() {local i
  for (i=nCA3max; i < nCA3max+nCA3b; i=i+1) {
    CA3list.o(i).stim.number = CNUM
    CA3list.o(i).stim.start = CSTART
    CA3list.o(i).stim.interval = CINT
    CA3list.o(i).stim.noise = CNOISE
    CA3list.o(i).stim.burstint = CBINT
    CA3list.o(i).stim.burstlen = CBLEN
    ncCA3list.o(i).weight = CAWGTb	
    ncCA3list.o(i).delay = CDEL
    ncCA3Nlist.o(i).weight = CNWGTb	
    ncCA3Nlist.o(i).delay = CDEL
  }
  // silence any extra synapses
  for (i=nCA3max+nCA3b; i < nCA3max+nCA3bmax; i=i+1) {
    CA3list.o(i).stim.number = 0
    ncCA3list.o(i).weight = 0	
    ncCA3Nlist.o(i).weight = 0	
  }
}

proc setEC() {local i
  for (i=0; i < nEC; i=i+1) {
    EClist.o(i).stim.number = ECNUM
    EClist.o(i).stim.start = ECSTART
    EClist.o(i).stim.interval = ECINT
    EClist.o(i).stim.noise = ECNOISE
    EClist.o(i).stim.burstint = ECBINT
    EClist.o(i).stim.burstlen = ECBLEN
    ncEClist.o(i).weight = ECWGT	
    ncEClist.o(i).delay = ECDEL
    ncECNlist.o(i).weight = ECNWGT	
    ncECNlist.o(i).delay = ECDEL
  }
  // silence any extra synapses
  for (i=nEC; i < nECmax; i=i+1) {
    EClist.o(i).stim.number = 0
    ncEClist.o(i).weight = 0	
    ncECNlist.o(i).weight = 0	
  }
}

proc setBC() {local i
  for (i=0; i < nBC; i=i+1) {
    BClist.o(i).stim.number = BCNUM
    BClist.o(i).stim.start = BCSTART
    BClist.o(i).stim.interval = BCINT
    BClist.o(i).stim.noise = BCNOISE
    BClist.o(i).stim.burstint = BCBINT
    BClist.o(i).stim.burstlen = BCBLEN
    ncBClist.o(i).weight = BCWGT	
    ncBClist.o(i).delay = BCDEL
  }
}

proc setBSC() {local i
  for (i=0; i < nBC; i=i+1) {
    BSClist.o(i).stim.number = BSCNUM
    BSClist.o(i).stim.start = BSCSTART
    BSClist.o(i).stim.interval = BSCINT
    BSClist.o(i).stim.noise = BSCNOISE
    BSClist.o(i).stim.burstint = BSCBINT
    BSClist.o(i).stim.burstlen = BSCBLEN
    ncBSClist.o(i).weight = BSCWGT	
    ncBSClist.o(i).delay = BSCDEL
  }
}

proc showsyn() {
//cell.showsyn()	// show all synapses
cell.showlayersyn(0, $1*2-1, 2, 1)	// CA3 apical synapses
cell.showlayersyn(nCA3max*2, (nCA3max+$1)*2-1, 5, 0)	// CA3 basal synapses
cell.showlayersyn((nCA3max+nCA3bmax)*2, (nCA3+nCA3b+$1)*2-1, 3, 0)	// EC synapses
//cell.showlayersyn((nCA3+nCA3b+nEC)*2, (nCA3+nCA3b+nEC)*2+nBC-1, 4, 0)	// BC synapses
//cell.showlayersyn((nCA3+nCA3b+nEC)*2+nBC, (nCA3+nCA3b+nEC)*2+nBC+nBSC-1, 3, 0)	// BSC synapses
}

proc analcamx() {localobj cam	// analyse max ca across spine heads
// parameters provide spine list and start and end indices of required spines
  cam=new Vector()
  forsec $o1 {
      cam.append(camax_dca(0.5))
  }
  if ($2 <= $3) {
    print cam.mean($2,$3), cam.max($2,$3), cam.min($2,$3), cam.stdev($2,$3)
  }
}

proc analcasp() {	// analyse max ca across spine heads
// parameters provide start and end indices of required spines
// assumes that spines are present in all layers
  print "EC spines"
  analcamx(cell.spine_list, nCA3max+nCA3bmax, nCA3max+nCA3bmax+nEC-1)
  print "SR spines"
  analcamx(cell.spine_list, 0, nCA3-1)
  print "SO spines"
  analcamx(cell.spine_list, nCA3max, nCA3max+nCA3b-1)
}

proc makexsyns() {
xpanel("Synapses")
xlabel("CA3 apical")
xvalue("Number", "nCA3", 1, "setCA3()")
xvalue("AMPA", "CAWGT", 1, "setCA3()")
xvalue("NMDA", "CNWGT", 1, "setCA3()")
xlabel("CA3 basal")
xvalue("Number", "nCA3b", 1, "setCA3b()")
xvalue("AMPA", "CAWGTb", 1, "setCA3b()")
xvalue("NMDA", "CNWGTb", 1, "setCA3b()")
xlabel("EC")
xvalue("Number", "nEC", 1, "setEC()")
xvalue("AMPA", "ECWGT", 1, "setEC()")
xvalue("NMDA", "ECNWGT", 1, "setEC()")
xlabel("GABAA")
xvalue("BC", "BCWGT", 1, "setBC()")
xvalue("BSC", "BSCWGT", 1, "setBSC()")
xpanel()
}

proc makexchans() {
xpanel("Ion Channels")
xlabel("KA")
xvalue("gka", "cell.gka", 1, "cell.set_dendrite()")
xlabel("Ih")
xvalue("gh", "cell.ghd", 1, "cell.set_dendrite()")
xpanel()
}

proc makexstim() {
xpanel("Stimuli")
xlabel("CA3 apical")
xvalue("Start time", "CSTART", 1, "setCA3()")
xvalue("Total spikes", "CNUM", 1, "setCA3()")
xvalue("Spike interval", "CINT", 1, "setCA3()")
xvalue("Interval noise", "CNOISE", 1, "setCA3()")
xvalue("Burst interval", "CBINT", 1, "setCA3()")
xvalue("Burst length", "CBLEN", 1, "setCA3()")
xlabel("CA3 basal")
xvalue("Start time", "CSTART", 1, "setCA3b()")
xvalue("Total spikes", "CNUM", 1, "setCA3b()")
xvalue("Spike interval", "CINT", 1, "setCA3b()")
xvalue("Interval noise", "CNOISE", 1, "setCA3b()")
xvalue("Burst interval", "CBINT", 1, "setCA3b()")
xvalue("Burst length", "CBLEN", 1, "setCA3b()")
xlabel("EC")
xvalue("Start time", "ECSTART", 1, "setEC()")
xvalue("Total spikes", "ECNUM", 1, "setEC()")
xvalue("Spike interval", "ECINT", 1, "setEC()")
xvalue("Interval noise", "ECNOISE", 1, "setEC()")
xvalue("Burst interval", "ECBINT", 1, "setEC()")
xvalue("Burst length", "ECBLEN", 1, "setEC()")
xpanel()
}

proc makexplots() {
xpanel("Plots")
xlabel("Max voltage plots")
xbutton("Spine heads", "cell.plotvmx(cell.spine_list)")
xbutton("Dendrites", "cell.plotvmx(cell.dendrite_list)")
xbutton("Apical", "cell.plotvmx(cell.apical_list)")
xbutton("Apical trunk", "cell.plotvmx(cell.trunk_list)")
xbutton("Apical obliques", "cell.plotvmx(cell.oblique_list)")
xbutton("SR", "cell.plotvmx(cell.SR_list)")
xbutton("SLM", "cell.plotvmx(cell.SLM_list)")
xbutton("Basal", "cell.plotvmx(cell.basal_list)")
xlabel("Max calcium plots")
xbutton("Spine heads", "cell.plotcamx(cell.spine_list, tot_spines, 1.0)")
//xbutton("Anal spines", "analcasp()")
xbutton("Dendrites", "cell.plotcamxd(cell.dendrite_list)")
xbutton("Apical", "cell.plotcamxd(cell.apical_list)")
xbutton("Apical trunk", "cell.plotcamxd(cell.trunk_list)")
xbutton("Apical obliques", "cell.plotcamxd(cell.oblique_list)")
xbutton("SR", "cell.plotcamxd(cell.SR_list)")
xbutton("SLM", "cell.plotcamxd(cell.SLM_list)")
xbutton("Basal", "cell.plotcamxd(cell.basal_list)")
xpanel()
}


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