Electrostimulation to reduce synaptic scaling driven progression of Alzheimers (Rowan et al. 2014)

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Accession:154096
"... As cells die and synapses lose their drive, remaining cells suffer an initial decrease in activity. Neuronal homeostatic synaptic scaling then provides a feedback mechanism to restore activity. ... The scaling mechanism increases the firing rates of remaining cells in the network to compensate for decreases in network activity. However, this effect can itself become a pathology, ... Here, we present a mechanistic explanation of how directed brain stimulation might be expected to slow AD progression based on computational simulations in a 470-neuron biomimetic model of a neocortical column. ... "
Reference:
1 . Rowan MS, Neymotin SA, Lytton WW (2014) Electrostimulation to reduce synaptic scaling driven progression of Alzheimer's disease. Front Comput Neurosci 8:39 [PubMed]
Citations  Citation Browser
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network;
Brain Region(s)/Organism: Neocortex;
Cell Type(s): Neocortex L5/6 pyramidal GLU cell; Neocortex L2/3 pyramidal GLU cell; Neocortex V1 interneuron basket PV GABA cell; Neocortex fast spiking (FS) interneuron; Neocortex spiny stellate cell; Neocortex spiking regular (RS) neuron; Neocortex spiking low threshold (LTS) neuron;
Channel(s):
Gap Junctions:
Receptor(s): GabaA; AMPA; NMDA;
Gene(s):
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON; Python;
Model Concept(s): Long-term Synaptic Plasticity; Aging/Alzheimer`s; Deep brain stimulation; Homeostasis;
Implementer(s): Lytton, William [bill.lytton at downstate.edu]; Neymotin, Sam [Samuel.Neymotin at nki.rfmh.org]; Rowan, Mark [m.s.rowan at cs.bham.ac.uk];
Search NeuronDB for information about:  Neocortex L5/6 pyramidal GLU cell; Neocortex L2/3 pyramidal GLU cell; Neocortex V1 interneuron basket PV GABA cell; GabaA; AMPA; NMDA; Gaba; Glutamate;
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RowanEtAl2014
batchscripts
mod
README
alz.hoc
alzinfo.m
autotune.hoc *
basestdp.hoc *
batch.hoc *
batch2.hoc *
batchcommon
checkirreg.hoc *
clusterrun.sh
col.dot *
col.hoc *
comppowspec.hoc *
condisconcellfig.hoc *
condisconpowfig.hoc *
declist.hoc *
decmat.hoc *
decnqs.hoc *
decvec.hoc *
default.hoc *
drline.hoc *
e2hubsdisconpow.hoc *
e2incconpow.hoc *
filtutils.hoc *
flexinput.hoc
geom.hoc *
graphplug.hoc *
grvec.hoc *
infot.hoc *
init.hoc *
labels.hoc *
load.hoc *
local.hoc *
makepopspikenq.hoc *
matfftpowplug.hoc *
matpmtmplug.hoc *
matpmtmsubpopplug.hoc *
matspecplug.hoc *
mosinit.hoc
network.hoc *
nload.hoc *
nqpplug.hoc *
nqs.hoc *
nqsnet.hoc *
nrnoc.hoc *
params.hoc
plot.py
plotavg.py
plotbatch.sh
plotbatchcluster.sh
plotdeletions.py
plotntes.py
powchgtest.hoc *
pyhoc.py
python.hoc *
pywrap.hoc *
ratlfp.dat *
redE2.hoc *
run.hoc
runsim.sh
setup.hoc *
shufmua.hoc *
sim.hoc
simctrl.hoc *
spkts.hoc *
stats.hoc *
syncode.hoc *
vsampenplug.hoc *
writedata.hoc
xgetargs.hoc *
                            
// $Id: run.hoc,v 1.66 2011/12/28 22:14:56 samn Exp $
print "Loading run.hoc..."
objref wf1,wf2,wrec
sprint(tstr,"o[%d]",numcols)
declare("vit",tstr,"nqLFP",tstr,"SPKSZ",20000e3)
//declare("vit",tstr,"nqLFP",tstr,"SPKSZ",12e3)
 // {wf1=new File() wf2=new File()}
// wrec = new NQS("time","ID","SYN","WT")
// wrec.zvec(2e7) // make big enough?

method("local") // why was this being used?
method("global")
cvode.atol(1e-3) 
cvode.condition_order(1) // irrelevant to acells?
declare("sepflds",0) // whether to record separate fields for each layer

// rv2 is part of grvec.hoc, as a stub, so it can be
// customized to do something to vector before graphing it
proc rv2 () { }

//** draw lines between cell subpopulations
proc rasterlines () { localobj o
  g=graphItem
  for ct=0,CTYPi-1 if(col.numc[ct]) {
    drline(0,col.ixe[ct],mytstop,col.ixe[ct],g,2,6)
    // o=mdl2view(g,0,ix[ii]+numc[ii]/10)
    o=mdl2view(g,0.9,col.ix[ct]+col.numc[ct]/4)
    g.label(0.9,o.x[3],CTYP.o(ct).s)
  }
  g.flush
}
//** calls rasterlines, making sure g is set first
proc grlines () { 
  {g=Graph[$1] rasterlines()}
}

proc a () { local sh,sv
  if(g==nil)gg()
  if (!isobj(aa,"Graph")) aa=g else g=aa
  if (aa.view_count==0) aa=g
  sv=gnum gnum=ojtnum(g)
  graphItem=g
  sh=0 grv_.super=1 g.erase_all
  grv_.gveraseflag=0  grv_.gvmarkflag=grv_.super=1 // gnum=0
  gv(0,1+sh,2) // gv(1,3+sh,2) gv(2,2+sh,2)
  grv_.gvmarkflag=grv_.super=0
  gnum=sv
  rasterlines()
}
proc b () { rewt() time() a() }

//** init - called @ start of run
proc init () { 
  initMisc1()
  vseed_stats(392426)
  finitialize() 
  cvode.re_init()
}

//** initrr - for doing a rerun - not used right now
proc initrr () { 
  rewt()
  col.intf.global_init()
  NStim[0].global_init()
  vseed_stats(392426)
}

//** setMemb - nothing here
proc setMemb () {}

//** initMisc1
proc initMisc1 () { local i
  col.intf.global_init()
  for i=0,numcols-1 col[i].cstim.initrands()
}

objref ww // global ww for post processing
{wwht_INTF6=1 wwwid_INTF6=100}
//** wrecon - setup LFP recording, one LFP for each COLUMN
proc wrecon () { local cdx,ii,x,ct,cnt localobj tl,vm
  tl=new List()
  for cdx=0,numcols-1 {
    nqsdel(nqLFP[cdx])
    if(sepflds) nqLFP[cdx]=new NQS("E2","E4","E5","E6","LFP") else {nqLFP[cdx]=new NQS(1) nqLFP[cdx].s[0].s="LFP"}
    {nqLFP[cdx].v.resize(tstop/vdt_INTF6) nqLFP[cdx].pad()}
    for ii=0,nqLFP[cdx].m-1 tl.append(nqLFP[cdx].v[ii])
  }
  {vm=new Vector(CTYPi) vm.x(E2)=0 vm.x(E4)=1 vm.x(E5R)=vm.x(E5B)=2 vm.x(E6)=3}
  col.intf.initwrec(tl)
  for x=0,numcols-1 {
    for case(&ct,E2,E4,E5R,E5B,E6) {
      for ii=col[x].ix[ct],col[x].ixe[ct] {
        if(sepflds) {
          col[x].ce.o(ii).wrc(vm.x(ct)+x*5)
          col[x].ce.o(ii).wrc(4+x*5)
        } else col[x].ce.o(ii).wrc(x)
      }
    }
  }
}

//** wrecoff - turn off LFP recording
proc wrecoff () { local ct
  for ctt(&ct) for ixt(ct) XO.wrec(0)
}

//** finishMisc - called @ end of run()
func finishMisc () { local ii localobj co
  for ltr(XO,printlist) if (isassigned(XO.o)) if (XO.o.fflag) XO.o.fini
  // if(0) panobj.pvplist(ofile,params,100) //dont save printlist for now
  col.intf.global_fini
  for ltr(co,lcol) co.intf.spkstats2(1)
  print "TMAX: ",tmax_INTF6
  return 1
}

//** snapsv() save after printlist items min-max to fixed dt
proc snapsv () { local a,vdt,min,max localobj v1,o
  grv_.bst(3,3)
  vdt=0.2 
  a=allocvecs(v1)
  v1.resize(tstop/vdt)
  for ltr(o,printlist) { 
    if (o.code!=3) continue
    v1.snap(o.vec,o.tvec,vdt)
    o.vec.copy(v1)
    o.pstep=vdt
    o.tvflag=0
  }
  if (numarg()==0) grv_.pvall()
  dealloc(a)
}

proc exeruncall () { for ltr(XO,printlist) if (XO.code==3) XO.tvflag=1 }
proc pvout2 () { snapsv(1) }

//printlist=new List()
if(printlist==nil)printlist=new List()
proc prlclr () { localobj ce,col,intf
  for ltr(XO,printlist) {
    if (isassigned(XO.o)) if (XO.o.fflag) XO.o.recclr
  }
  //  for ltr(XO,ce) XO.wrc(-1)
  for ltr(col,lcol) {
    {ce=col.ce intf=ce.o(0)}
    for ii=0,ce.count-1 ce.o(ii).wrc(-1)
    intf.wwfree(0)
  }
  printlist.remove_all
}

//** prl(recv,recs[,lvextra]) - setup recording in printlist
//$1  = whether to record any cell voltages, default off
//$2  = whether to record spike times, default on
//$o3 = extra cells to record. lv.o(0)=cell,lv.o(1)=param to record,etc.,optional
proc prl () { local a,x,cidx,ii,jj,offst,y,recv,recs,max localobj xo,lvextra,co,ce
  if(numarg()>0) recv=$1 else recv=0
  if(numarg()>1) recs=$2 else recs=1
  if(numarg()>2) lvextra=$o3 else lvextra=nil
  {offst=0 prlclr()}
  for ltr(co,lcol,&ii) {
    {ce=co.ce intf=co.intf}
    if (recs) { sprint(tstr,"%s_SPKS",co.name)
      if (intf.flag("jcn")) { // for use with jitcon()
        printlist.append((vit[ii]=new vitem(tstr,SPKSZ,1)))
        intf.jitrec(vit[ii].vec,vit[ii].tvec)
      } else {
        intf.jitrec() // clear jit recording
        for ltr(xo,ce,&y) {
          if (y==0) vit[ii]=new_printlist_nc(xo, xo.id, tstr) else {
            new_printlist_nc2(vit[ii], xo, xo.id)        }
        }
      }
    }
    npacsz=20
    if (recv && ce.count>0) for x=0,CTYPi-1 {
      if (co.numc[x]>2) max=2 else max=co.numc[x]-1
      for jj=0,max {
        XO=ce.object(co.ix[x]+jj)
        XO.recclr
        new_printlist_ac(XO,"V",  CTYP.o(x).s,XO.id)
        // new_printlist_ac(XO,"VGB",  CTYP.o(x).s,XO.id)
        // new_printlist_ac(XO,"VGA",  CTYP.o(x).s,XO.id)
        // new_printlist_ac(XO,"VGA2",  CTYP.o(x).s,XO.id)
        // new_printlist_ac(XO,"VAM2",  CTYP.o(x).s,XO.id)
        // new_printlist_ac(XO,"AHP",  CTYP.o(x).s,XO.id)
        //      printlist.o(printlist.count-1).code=3 // use code 3 for snapping
        // XO=ce.object(ixe[x]-jj-1)
        // XO.recclr
        // new_printlist_ac(XO,"V",  CTYP.object(x).s,XO.id)
      }
    }
    if(lvextra!=nil){
      for(jj=0;jj<lvextra.count;jj+=2){ XO=lvextra.o(jj)
        new_printlist_ac(XO,lvextra.o(jj+1).s,CTYP.object(ctyp(XO.id)).s,XO.id)
      }
    }
  }
  if (use_nqLFP) {
    wrecon()
  }
}
 
flddur=celdur=1000
splshhsz=0.4
objref slicepictypes
slicepictypes=new Vector()
slicepictypes.append(0,3,2)
stopoq_INTF6=1

proc rer () { 
  intf.resetall
  prl()
  shock()
  srun()
}

proc turnoff () { local cel0,cel1,off
  cel0=$1 cel1=$2
  if (argtype(3)==0) off=$3 else off=0
  ind.indgen(ix[cel0],ixe[cel0],1) vec.indgen(ix[cel1],ixe[cel1],1) 
  intf.turnoff(ind,vec,off)
}

//** turn off intralaminar connections
proc intralamoff () { local ct
  for ctt(&ct) if(numc[ct] && div[ct][ct][0]) turnoff(ct,ct)
}

//** turn on intralaminar connections
proc intralamon () { local ct
  for ctt(&ct) if(numc[ct] && div[ct][ct][0]) turnoff(ct,ct,1)
}

load_file("spkts.hoc")
objref snq,fnq,anq,cvnq
//get CVPNQS
proc getcvnq () {
  if(cvnq!=nil)nqsdel(cvnq)
  if(numarg()==0) cvnq=CVPNQS(snq,1,1,0)
  if(numarg()==1) cvnq=CVPNQS(snq,$1,1,0)
  if(numarg()==2) cvnq=CVPNQS(snq,$1,$2,0)
  if(numarg()==3) cvnq=CVPNQS(snq,$1,$2,$3)
}
//get PActNQS
proc getanq () {
  if(anq!=nil)nqsdel(anq)
  if(numarg()==0) {
    anq=PActNQS(snq)
  } else if(numarg()==1) {
    anq=PActNQS(snq,$1) 
  } else if(numarg()==2) {
    anq=PActNQS(snq,$1,$2) 
  }
}
//get SpikeNQS
proc getsnq () {
  if(snq!=nil)nqsdel(snq)
  snq=SpikeNQS(printlist.o(0),0)
}
//get SpikeNQS,FreqNQS
proc getsfnq () {
  getsnq()
  if(fnq!=nil)nqsdel(fnq)
  fnq=FreqNQS(snq,20,1,0)
}
//display & print average vals of snq,fnq
proc dispfnq () { local ct
  fnq.verbose=0
  for ctt(&ct) {
    fnq.select("Type",ct,"StartT","<=",tmax_INTF6)
    printf("%s mean F = %g Hz\n",CTYP.o(ct).s,fnq.getcol("Freq").mean)
    fnq.gr("Freq","EndT",0,clr,1)
    clr+=1
  }
}

//draw $2 cell type in $3 color from PActNQS $o1
proc dispPActNQ () { local ct,color localobj anq,str  
  anq=$o1 ct=$2 color=$3 str=new String() str.s="act"
  if(numarg()>3)str.s=$s4
  anq.select("ct",ct)
  gvmarkflag=0
  anq.gr(str.s,"ts",0,color,9)
  gvmarkflag=1
  anq.gr(str.s,"ts",0,color,10)
  gvmarkflag=0
}

//* function calls
//prl(1,1)
prl(0,1) // disable printlist voltage recording for long runs to save RAM