Multitarget pharmacology for Dystonia in M1 (Neymotin et al 2016)

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Accession:189154
" ... We developed a multiscale model of primary motor cortex, ranging from molecular, up to cellular, and network levels, containing 1715 compartmental model neurons with multiple ion channels and intracellular molecular dynamics. We wired the model based on electrophysiological data obtained from mouse motor cortex circuit mapping experiments. We used the model to reproduce patterns of heightened activity seen in dystonia by applying independent random variations in parameters to identify pathological parameter sets. ..."
Reference:
1 . Neymotin SA, Dura-Bernal S, Lakatos P, Sanger TD, Lytton WW (2016) Multitarget Multiscale Simulation for Pharmacological Treatment of Dystonia in Motor Cortex. Front Pharmacol 7:157 [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network; Molecular Network;
Brain Region(s)/Organism: Neocortex;
Cell Type(s): Neocortex V1 L6 pyramidal corticothalamic cell; Neocortex U1 L2/6 pyramidal intratelencephalic cell; Neocortex V1 interneuron basket PV cell; Neocortex fast spiking (FS) interneuron; Neocortex spiking regular (RS) neuron; Neocortex spiking low threshold (LTS) neuron; Neocortex layer 4 neuron; Neocortex layer 2-3 interneuron; Neocortex layer 4 interneuron; Neocortex layer 5 interneuron; Neocortex layer 6a interneuron;
Channel(s): I A; I h; I_SERCA; Ca pump; I K,Ca; I Calcium; I L high threshold; I T low threshold; I N; I_KD; I M; I Na,t;
Gap Junctions:
Receptor(s): GabaA; GabaB; AMPA; mGluR;
Gene(s): HCN1;
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON; Python;
Model Concept(s): Oscillations; Activity Patterns; Beta oscillations; Reaction-diffusion; Calcium dynamics; Pathophysiology; Multiscale;
Implementer(s): Neymotin, Sam [samn at neurosim.downstate.edu]; Dura-Bernal, Salvador [salvadordura at gmail.com];
Search NeuronDB for information about:  Neocortex V1 L6 pyramidal corticothalamic cell; Neocortex V1 interneuron basket PV cell; Neocortex U1 L2/6 pyramidal intratelencephalic cell; GabaA; GabaB; AMPA; mGluR; I Na,t; I L high threshold; I N; I T low threshold; I A; I M; I h; I K,Ca; I Calcium; I_SERCA; I_KD; Ca pump; Gaba; Glutamate;
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dystdemo
readme.txt
cagk.mod
cal.mod *
calts.mod *
can.mod *
cat.mod *
gabab.mod
h_winograd.mod
HCN1.mod
IC.mod *
icalts.mod *
ihlts.mod *
kap.mod
kcalts.mod *
kdmc.mod
kdr.mod
km.mod *
mglur.mod *
misc.mod *
MyExp2SynBB.mod *
MyExp2SynNMDABB.mod
nax.mod
stats.mod *
vecst.mod *
aux_fun.inc *
conf.py
declist.hoc *
decnqs.hoc *
decvec.hoc *
default.hoc *
drline.hoc *
geom.py
ghk.inc *
grvec.hoc
init.hoc
labels.hoc
labels.py *
local.hoc *
misc.h
mpisim.py
netcfg.cfg
nqs.hoc *
nqs.py
nrnoc.hoc *
pyinit.py *
python.hoc *
pywrap.hoc *
simctrl.hoc *
simdat.py
syn.py
syncode.hoc *
vector.py *
xgetargs.hoc *
                            
// $Id: xgetargs.hoc,v 1.20 2008/05/11 17:19:11 billl Exp $

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
  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
}