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]
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 L5/6 pyramidal GLU cell; Neocortex U1 L2/6 pyramidal intratelencephalic GLU cell; Neocortex V1 interneuron basket PV GABA 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 [Samuel.Neymotin at nki.rfmh.org]; Dura-Bernal, Salvador [salvadordura at gmail.com];
Search NeuronDB for information about:  Neocortex L5/6 pyramidal GLU cell; Neocortex V1 interneuron basket PV GABA cell; Neocortex U1 L2/6 pyramidal intratelencephalic GLU 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: labels.hoc,v 1.104 2012/04/12 01:44:03 samn Exp $

print "Loading labels.hoc..."

{load_file("declist.hoc")}
// keep track of version number for future changes
// eg if (label_hoc_vers>88) rcsopen("labels.hoc",88) // go back to 88
labels_hoc_vers=find_num("$Id: labels.hoc,v 1.104 2012/04/12 01:44:03 samn Exp $","1\\."," ")
objref NCv,CODEv,DELv
objref PRIDv,POIDv,PRv,POv,DISTv,WT0v,WT1v // mo(1) will assign these
{declare("ce",nil,"CTYP",new List(),"CPLA",new List(),"TPA",new List(),"nm",new List())}
{declare("STYP",new List(),"ncells",0,"ZTYP",new List(),"INCOL",new List())}
{declare("DEND",0,"SOMA",1,"AXON",2)} // compartment codes - only 3 for now

scrsz=50*1e3
double scr[scrsz]

//* utility functions
// plmin(val,var)
func plmin() { return $1 + $2*(2*u_rand() - 1) } 

//* cell types: 
// iex(), returns numeric index associated with a string or string object
func iex () { 
  if (argtype(1)==2) sprint(tstr,"x=%s",$s1) else sprint(tstr,"x=%s",$o1.s)
  execute(tstr) return x 
}
// ice(), returns whether cell is an inhib cell based on its name starting with I
func ice () { local x
  if (argtype(1)==2) return strm($s1,"^I")
  if (argtype(1)==0) x=$1 else if (argtype(1)==1) x=$o1.type 
  return strm(CTYP.o(x).s,"^I")
}
//* GetLyr - return layer of type
func GetLyr () { local x localobj st
  st=new String()
  if (argtype(1)==2) st.s=$s1 else if (argtype(1)==0) st.s=CTYP.o($1).s else {
    st.s=CTYP.o($o1.type).s }
  sscanf(st.s,"%*1s%d",&x)
  return x
}

proc printtype () { local i
  for (i=1;argtype(i)==0;i+=1) if ($i!=-1) printf("%s(%d) ",CTYP.o($i).s,$i)
  if (argtype(i)==2) printf("%s",$si) else print ""
}
proc celltype () { localobj st
  st=new String("\n")
  if (argtype(2)==2) st.s=$s2
  if (argtype(1)==0) printtype(ce.o($1).type,st.s) else printtype($o1.type,st.s) 
}

obfunc names2indices () { local x localobj lo,xo,st
  lo=new List() st=new String()
  split($s1,lo)
  for ltr(xo,lo,&x) { sprint(st.s,"%s=%d",xo.s,x) execute(st.s) }
  return lo
}

// at some point may want to divide up this list into cell type -- eg RS,IB and location
CTYP=names2indices("NU,SM,DP,SU,IN,TC,IRE,ITH,E6,E6C,I6,I6C,I6L,E5P,E5B,E5R,I5,I5L,E4,I4,I4L,E2,E2B,I2,I2Q,I2C,I2L,RS,IB,LTS,FS,ECA1,ICA1,ICA1L,EDG,IDG,IDGL,ECA3,ICA3,ICA3L,E3,I3,I3L,ES,IS,ISL,EM,IM,IML,EV,IV,IVL,TCM,IREM,HTC")
CTYPi=CTYP.count  // number of cell types
EXCIT=-1  // don't know how to fit these in best
INHIB=-2

// 1 cmp nrn, 2 cmp nrn, multi cmp nrn, intfire1, INTF, invlfire, nstim
for scase2(XO,"1-CMP","CMP1","2-CMP","CMP2","MULTI-CMP","MC","IntFire1","IF1","INTF","IF",\
          "INVLF","IFV","NStim","STM") { CPLA.append(XO)
  sprint(tstr,"%s=%d",XO.t,i1) execute(tstr) }
CPLAi=CPLA.count // count of cell templates

for scase2(XO,"REAL","RL","ARTC","AC","SOMA","SO","DEND","DN") {TPA.append(XO)}
TPAi=TPA.count

proc ae () { localobj xo
  STYP.remove_all
  for scase2(xo,"AMPA","AM","NMDA","NM","GABAA","GA","GABAB","GB",\
             "AMPA2","AM2","NMDA2","NM2","GABAA2","GA2","GABAB2","GB2",\
             "IClamp","IC","AMPA/NMDA","EX","GABAA/GABAB2","IX",\
             "Exp2Syn","E2Sy","mGluR","MG"){
    STYP.append(new String2(xo.t,xo.s)) // switch them around here
    sprint(tstr,"%s=%d",xo.t,i1)
    execute(tstr)
  }
  STYPi=STYP.count  // number of cell types
}
ae()

for scase(XO,"DG","CA3","CA1","SUB","PSUB","MEC","LEC") {
  sprint(tstr,"%s=%d",XO.s,i1) execute(tstr) ZTYP.append(new String(XO.s))
}

for scase2(XO,"RIGHT","RIT","INCOL","INC","LEFT","LFT") { INCOL.append(new String(XO.s))
  sprint(tstr,"%s=%d",XO.t,i1) execute(tstr) }
INCOLi=INCOL.count

//* IsLTS - return if type is LTS
func IsLTS () {
  return $1 == I2L || $1 == I4L || $1 == I5L || $1 == I6L || $1 == ISL || $1 == IML || $1 == IVL
}
//* IsBurst - return if type is intrinsically bursting
func IsBurst () {
  return $1 == E2B || $1 == E5B
}
//* IsFRB - return true if type is fast regular bursting
func IsFRB () {
  return $1 == E2B
}
//* IsRS - return true if type is regular spiking E cell
func IsRS () {
  return $1 == E2 || $1 == E4 || $1 == E5R || $1 == E6 || $1 == ES || $1 == EM || $1 == EV
}
//* IsFS - return true if type is fast spiking interneuron
func IsFS () {
  return $1==I2 || $1==I4 || $1==I5 || $1==I6 || $1==ICA3 || $1==IDG || $1==ICA1 || $1==IS || $1==IM || $1==IV
}
//* IsTHAL - return true if type is from thalamus
func IsTHAL () {
  return $1 == TC || $1 == IRE || $1 == TCM || $1 == IREM || $1 == HTC
}

func isartcell () { return sfunc.is_point_process($o1) }


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