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]
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 V1 pyramidal corticothalamic L6 cell; Neocortex V1 pyramidal intratelencephalic L2-5 cell; Neocortex V1 interneuron basket PV 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 [billl at neurosim.downstate.edu]; Neymotin, Sam [samn at neurosim.downstate.edu]; Rowan, Mark [m.s.rowan at cs.bham.ac.uk];
Search NeuronDB for information about:  Neocortex V1 pyramidal corticothalamic L6 cell; Neocortex V1 pyramidal intratelencephalic L2-5 cell; Neocortex V1 interneuron basket PV cell; GabaA; AMPA; NMDA; Gaba; Glutamate;
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RowanEtAl2014
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xgetargs.hoc *
                            
// $Id: xgetargs.hoc,v 1.20 2008/05/11 17:19:11 billl Exp $

print "Loading xgetargs.hoc..."

xgahfl=0
{load_file("decvec.hoc")}
strdef mesg
objref xgabxl,xgabxo

//* xgetargs()
// xgetargs(panel_name,command,arg1[,arg2,...],defaults) // existing or new params -- flag 2
//   may have no named params in this case since just set with call to command
//   eg xgetargs("New","redo","do this","do that","1,2")
// xgetargs(panel_name,command,"a1,a2,..") // existing params -- flag 1
// xgetargs(panel_name,command,strlist)
// xgetargs(1,...) // dismiss after setting
// xgetargs(list,...) // list of helper functions returned by xgetclrfunc()
// eg xgetargs("Random session","newrand","# of patts","patt size  ","overlap   ","5,33,7")
// optional 1st arg flag=1 means to remove panel after command is called
// Union contains: o[0]=VBox, o[1]=argv, [o[2]=param name list] o[3]=orig update
//                 o[4]=helper functions
//                 x[0]=#args, x[1]=flag, x[2]=dismiss x[3-5] reserved for future use
//                 s=panel/button name,t=quit call,u=varlable,v=scratch
obfunc xgetargs () { local i,j,args,flag,dismiss,na localobj o,argv,vb,l,st,xo
  if (!isassigned(xgabxl)) xgabxl=new List()
  st=new String2()
  na=numarg()  
  dismiss=0 i=1 
  xgabxl.append(o=new Union())
  if (argtype(i)==0) { dismiss=$1 i+=1 }
  if (argtype(i)==1) {xo=$oi i+=1} else xo=xgetclrfunc()
  o.os(4,"funcs",xo) // list of helper functions
  o.xs(2,"dismiss",dismiss) // dismiss=1 means dismiss at end
  o.os(1,"argv",argv=new Vector(na))
  argv.resize(0)
  o.os(0,"vb",vb=new VBox())
  sprint(o.t,"xgaqt(%s)",o)
  vb.dismiss_action(o.t)
  o.s=$si i+=1 o.t=$si i+=1
  vb.intercept(1)
  xpanel(o.s)
  xvarlabel(o.u)
  sprint(o.v,"xgetexec(%s)",o)
  xbutton(o.s,o.v)
  excu("xgetbuttn",o.o[4],o)
  if (i==na) { // this should be a list of existing params
    o.xs(1,"flag",flag=1) // flag -- variables have names
    o.os(2,"plist",l=new List()) // list of param names
    if (argtype(i)==2) {
      split_interp=1
      split($si,l) // list of strings
      split($si,argv) // list of values
    } else if (argtype(i)==1) {
      for ltr(xo,$oi) {
        l.append(xo)
        argv.append(str2num(xo.s))
      }
    } else { printf("xgetargs ERRA\n") xpanel() return o=nil}
    args=argv.size
    if (args==0) { // create them
      for ltr(xo,l) {
        sprint(st.s,"%s=1",xo.s) execute(st.s)
        args=l.count argv.resize(args) argv.fill(1)
      }
    } else if (args!=l.count) {printf("xgetargs ERRB %d %d\n",args,l.count) xpanel() return o=nil}
    o.os(3,"orig",argv.c)   // save original values
    o.xs(0,"nargs",args)
    excu("xgetlabl",o.o[4],o)
    for j=0,args-1 {
      sprint(o.v,"%s.x[%d]",argv,j)
      sprint(st.s,"xgetchg(%s,%d)",o,j)
      xvalue(l.o(j).t, o.v, 1, st.s, 1)
    }
  } else {
    j=i i=na
    if (strm($si,"^[a-z]")) { // a named variable; should all be name vars
      o.xs(1,"flag",flag=3) // flag -- variables have names and routine is called with args
      split_interp=1
      split($si,argv)
      o.os(2,"plist",l=new List()) // list of param names
      split($si,l) // list of strings
    } else {
      split_interp=0
      split($si,argv)
      o.xs(1,"flag",flag=2) // flag -- variables may have no names; are just args to a function
    }
    i=j // restore i
    o.xs(0,"nargs",args=argv.size)
    if (args!=na-i) { printf("xgetargs ERRC: mismatch %d %d\n",args,na-i) xpanel() return o=nil }
    o.os(3,"orig",argv.c)   // save original values
    for j=0,args-1 {
      sprint(o.v,"%s.x[%d]",argv,j)
      sprint(st.s,"xgetchg(%s,%d)",o,j)
      xvalue($si,o.v,1,st.s,1)
      if (flag==3) l.o(j).t=$si
      i+=1
    }
  }
  o.u=o.s // start with this label
  // xbutton("Help (2 clicks)","xgah()")
  xpanel()
  vb.intercept(0)
  vb.full_request(1)
  vb.map(o.s)
  xgabxo=o // global for current xgab object
  return o
}

//* xgah() should provide help -- doesn't
proc xgah () { 
  if (xgahfl==1) {
    continue_dialog("Press help button first, then elsewhere for button-specific help")
    xgahfl=0
  } else xgahfl=1
}

//* xgetclrfunc() -- set up the callbacks as empty functions
obfunc xgetclrfunc () { local flag localobj st,xo,o
  flag=0
  if (numarg()==1) if (isobj($o1,"List")) flag=1
  if (flag) { // just clear the functions
    for ltr(xo,$o1) xo.t="" // clear
    return $o1
  } else { // create
    st=new String() o=new List()
    for scase(st,"xgetchg2","xgetexec2","xgaqt2","xgetlabl","xgetbuttn") {
      o.append(new String2(st.s)) }
    if (numarg()==1) $o1=o
    return o
  }
}

//* xgetchg() done after a value is changed
proc xgetchg () { local i localobj o
  o=$o1 i=$2
print "A",o,i,o.o[4]
  if (excu("xgetchg2",o.o[4],o,i)) return
  sprint(o.u,"Press '%s' button for effect",o.s)
}

//* xgetexec() done when the 'make changes' button is pressed
proc xgetexec () { local i,args,dismiss,flag localobj o,l,av,vb,xo
  o=$o1
  if (excu("xgetexec2",o.o[4],o)) return
  args=o.x flag=o.x[1] dismiss=o.x[2] av=o.o[1] vb=o.o
  if (flag==1 || flag==3) {
    l=o.o[2]
    if (args!=l.count || args!=av.size) {
      printf("xgetexec() ERRA %d,%d,%d\n",args,l.count,av.size) return
    }
    for ltr(xo,l,&i) {
      sprint(o.v,"%s=%g",xo.s,av.x[i])
      execute(o.v)
    }
    if (flag==1) { // call the routine -- else will call below
      if (strm(o.t,"[(]")) o.v=o.t else sprint(o.v,"%s(%s)",o.t,o) // no args passed to function
    }
  }
  if (flag==2 || flag==3) {
    sprint(o.v,"%s(",o.t)
    for i=0,args-2 sprint(o.v,"%s%g,",o.v,av.x[i])
    sprint(o.v,"%s%g)",o.v,av.x[i]) 
  }
  execute(o.v)
  o.u="Changes submitted"
  if (dismiss) { xgaqt(o) // get rid of the box
  } else { o.o[3].copy(o.o[1]) } // new set of origs
}
  
//* xgaqt() called when the panel is dismissed
proc xgaqt () { local x localobj av,vb,o
  o=$o1 
  if (excu("xgaqt2",o.o[4],o)) return
  av=o.o[1] vb=o.o
  vb.unmap()
  if ((x=xgabxl.index(o))!=-1) xgabxl.remove(x)
  if (xgabxo==o) xgabxo=nil
}

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