In silico hippocampal modeling for multi-target pharmacotherapy in schizophrenia (Sherif et al 2020)

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Accession:258738
"Using a hippocampal CA3 computer model with 1200 neurons, we examined the effects of alterations in NMDAR, HCN (Ih current), and GABAAR on information flow (measured with normalized transfer entropy), and in gamma activity in local field potential (LFP). We found that altering NMDARs, GABAAR, Ih, individually or in combination, modified information flow in an inverted-U shape manner, with information flow reduced at low and high levels of these parameters. Theta-gamma phase-amplitude coupling also had an inverted-U shape relationship with NMDAR augmentation. The strong information flow was associated with an intermediate level of synchrony, seen as an intermediate level of gamma activity in the LFP, and an intermediate level of pyramidal cell excitability"
Reference:
1 . Sherif MA, Neymotin SA, Lytton WW (2020) In silico hippocampal modeling for multi-target pharmacotherapy in schizophrenia. NPJ Schizophr 6:25 [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: Hippocampus;
Cell Type(s): Hippocampus CA3 pyramidal GLU cell; Hippocampus CA3 interneuron basket GABA cell; Hippocampus CA3 stratum oriens lacunosum-moleculare interneuron;
Channel(s): I h;
Gap Junctions:
Receptor(s): AMPA; NMDA;
Gene(s): NR2A GRIN2A;
Transmitter(s): Glutamate; Gaba;
Simulation Environment: NEURON;
Model Concept(s): Schizophrenia;
Implementer(s): Sherif, Mohamed [mohamed.sherif.md at gmail.com];
Search NeuronDB for information about:  Hippocampus CA3 pyramidal GLU cell; Hippocampus CA3 interneuron basket GABA cell; AMPA; NMDA; I h; Gaba; Glutamate;
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CA3modelCode_npjSchizophrenia_September2020--main
data
README.md
CA1ih.mod
CA1ika.mod *
CA1ikdr.mod *
CA1ina.mod *
cagk.mod *
caolmw.mod *
capr.mod *
expsynstdp.mod
Gfluctp.mod *
HCN1.mod *
HCN2.mod
IA.mod
icaolmw.mod *
icapr.mod *
iholmkop.mod *
iholmw.mod *
ihpyrkop.mod *
ihstatic.mod *
infot.mod *
kahppr.mod *
kaolmkop.mod *
kapyrkop.mod *
kcaolmw.mod *
kcpr.mod *
kdrbwb.mod *
kdrolmkop.mod *
kdrpr.mod *
kdrpyrkop.mod *
km.mod
misc.mod *
MyExp2Syn.mod *
MyExp2SynAlpha.mod *
MyExp2SynBB.mod *
MyExp2SynNMDA.mod *
MyExp2SynNMDABB.mod *
nafbwb.mod *
nafolmkop.mod *
nafpr.mod *
nafpyrkop.mod *
samnutils.mod
sampen.mod
stats.mod
updown.mod *
vecst.mod *
wrap.mod *
analysisPlottingCode.py
aux_fun.inc *
batch.py
conf.py
declist.hoc *
decmat.hoc *
decnqs.hoc *
decvec.hoc *
default.hoc *
drline.hoc *
fig1sample.png
fig1simulationConfig.cfg
geom.py
grvec.hoc *
init.hoc
labels.hoc *
local.hoc *
misc.h
network.py
nqs.hoc *
nqs_utils.hoc *
nrnoc.hoc *
params.py
psd.py
pyinit.py
pywrap.hoc *
run.py
runone.py
simctrl.hoc *
stats.hoc *
syncode.hoc *
updown.hoc
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) }