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: pywrap.hoc,v 1.31 2012/08/04 03:19:13 samn Exp $ 

//* variables
declare("INITPYWRAP",0) // whether initialized properly

//* initialize pywrap
if(2!=name_declared("p")) {
  print "pywrap.hoc: loading python.hoc"
  load_file("python.hoc")
}
func initpywrap () { localobj pjnk
  INITPYWRAP=0
  if(2!=name_declared("p")){printf("initpywrap ERR0A: PythonObject p not found in python.hoc!\n") return 0}
  print p  
  pjnk=new PythonObject()
  if(!isojt(p,pjnk)){printf("initpywrap ERR0B: PythonObject p not found in python.hoc!\n")}
  if(!nrnpython("import numpy")) {printf("pypmtm ERR0C: could not import numpy python library!\n") return 0}
  INITPYWRAP=1
  return 1
}
initpywrap()

//** pypmtm(vec,samplingrate[,nw])
// this function calls python version of pmtm, runs multitaper power spectra, returns an nqs
obfunc pypmtm () { local sampr,spc,nw localobj vin,str,nqp,ptmp
  if(!INITPYWRAP) {printf("pypmtm ERR0A: python.hoc not initialized properly\n") return nil}
  if(!nrnpython("from mtspec import *")) {printf("pypmtm ERR0B: could not import mtspec python library!\n") return nil}  
/*  if(!nrnpython("import numpy")) {printf("pypmtm ERR0C: could not import numpy python library!\n") return nil}*/
  if(numarg()==0) {printf("pypmtm(vec,samplingrate)\n") return nil}
  vin=$o1 sampr=$2 str=new String()
  p.vjnk = vin.to_python()
  p.vjnk = p.numpy.array(p.vjnk)
  spc = 1.0 / sampr // "spacing"
  nw=4 if(numarg()>2) nw=$3
  sprint(str.s,"[Pxx,w]=mtspec(vjnk,%g,%d)",spc,nw)
  nrnpython(str.s)
  nqp=new NQS("f","pow")
  nqp.v.from_python(p.w)
  nqp.v[1].from_python(p.Pxx)
  return nqp
}

//** pybspow(vec,samplingrate[,maxf,pord])
// this function calls python version of bsmart, to get power pectrum, returns an nqs
// pord is order of polynomial -- higher == less smoothing. default is 12
obfunc pybspow () { local sampr,pord,maxf localobj vin,str,nqp,ptmp
  if(!INITPYWRAP) {printf("pybspow ERR0A: python.hoc not initialized properly\n") return nil}
  if(!nrnpython("from spectrum import ar")) {printf("pybspow ERR0B: could not import spectrum python library!\n") return nil}  
  if(numarg()==0) {printf("pybspow(vec,samplingrate)\n") return nil}
  vin=$o1 sampr=$2 str=new String()
  if(numarg()>2) maxf=$3 else maxf=sampr/2
  if(numarg()>3) pord=$4 else pord=64
  p.vjnk = vin.to_python()
  p.vjnk = p.numpy.array(p.vjnk)
  sprint(str.s,"Pxx,F=ar(vjnk,rate=%g,order=%d,maxfreq=%g)",sampr,pord,maxf)
  nrnpython(str.s)
  nqp=new NQS("f","pow")
  nqp.v[0].from_python(p.F)
  nqp.v[1].from_python(p.Pxx)
  return nqp
}

//** pyspecgram(vec,samplingrate[,orows])
// this function calls python version of specgram, returns an nqs
obfunc pyspecgram () { local sampr,spc,i,j,sz,f,tt,orows,a localobj vin,str,nqp,ptmp,vtmp
  if(!INITPYWRAP) {printf("pyspecgram ERR0A: python.hoc not initialized properly\n") return nil}
  if(!nrnpython("from matplotlib.mlab import specgram")) {printf("pyspecgram ERR0B: could not import specgram from matplotlib.mlab!\n") return nil}  
  if(numarg()==0) {printf("pyspecgram(vec,samplingrate)\n") return nil}
  a=allocvecs(vtmp)
  vin=$o1 sampr=$2 str=new String()
  if(numarg()>2)orows=$3 else orows=1
  p.vjnk = vin.to_python()
  p.vjnk = p.numpy.array(p.vjnk)
  sprint(str.s,"[Pxx,freqs,tt]=specgram(vjnk,Fs=%g)",sampr)
  nrnpython(str.s)
  if(orows) {
    {nqp=new NQS("f","pow") nqp.odec("pow")}
    {sz=p.Pxx.shape[0] nqp.clear(sz)}
    for i=0,sz-1 {
      {vtmp.resize(0) vtmp.from_python(p.Pxx[i]) f=p.freqs[i]}
      nqp.append(f,vtmp)
    }
  } else {
    nqp=new NQS("f","pow","t")
    sz = p.Pxx.shape[0]
    nqp.clear(sz * p.Pxx.shape[1])
    for i=0,sz-1 {
      {vtmp.resize(0) vtmp.from_python(p.Pxx[i]) f=p.freqs[i]}
      for j=0,vtmp.size-1 nqp.append(f,vtmp.x(j),p.tt[j])
    }
  }
  dealloc(a)
  return nqp
}

//** pycsd(vec1,vec2,samplingrate)
// this function calls python version of csd (cross-spectral density)
// returns an nqs with csd -- csd is non-directional
obfunc pycsd () { local sampr,a localobj v1,v2,str,nqp
  if(!INITPYWRAP) {printf("pycsd ERR0A: python.hoc not initialized properly\n") return nil}
  if(!nrnpython("from matplotlib.mlab import csd")) {printf("pycsd ERR0B: could not import csd from matplotlib.mlab!\n") return nil}  
  if(numarg()==0) {printf("pycsd(vec,samplingrate)\n") return nil}
  v1=$o1 v2=$o2 sampr=$3 str=new String()
  {p.vjnk1=v1.to_python() p.vjnk1=p.numpy.array(p.vjnk1)}
  {p.vjnk2=v2.to_python() p.vjnk2=p.numpy.array(p.vjnk2)}
  sprint(str.s,"[Pxy,freqs]=csd(vjnk1,vjnk2,Fs=%g)",sampr)
  nrnpython(str.s)
  nqp=new NQS("f","pow")
  nqp.v[0].from_python(p.freqs)
  nqp.v[1].from_python(p.Pxy)
  return nqp
}

//** pypsd(vec,samplingrate[,NFFT])
// this function calls python version of psd (power-spectral density)
// returns an nqs with psd
obfunc pypsd () { local sampr,NFFT localobj v1,str,nqp
  if(!INITPYWRAP) {printf("pypsd ERR0A: python.hoc not initialized properly\n") return nil}
  if(!nrnpython("from matplotlib.mlab import psd")) {printf("pypsd ERR0B: could not import psd from matplotlib.mlab!\n") return nil}  
  // nrnpython("from matplotlib.mlab import window_none")
  if(numarg()==0) {printf("pypsd(vec,samplingrate)\n") return nil}
  v1=$o1 sampr=$2 str=new String() 
  {p.vjnk1=v1.to_python() p.vjnk1=p.numpy.array(p.vjnk1)}
  if(numarg()>2) NFFT=$3 else NFFT=v1.size
  if(sz%2==1) sz+=1
  sprint(str.s,"[Pxx,freqs]=psd(vjnk1,Fs=%g,NFFT=%d)",sampr,NFFT)
  nrnpython(str.s)
  nqp=new NQS("f","pow")
  nqp.v[0].from_python(p.freqs)
  nqp.v[1].from_python(p.Pxx)
  return nqp
}

//** pycohere(vec1,vec2,samplingrate) 
// this function calls python version of cohere (coherence is normalized csd btwn vec1, vec2)
// returns an nqs with coherence
obfunc pycohere () { local sampr,a localobj v1,v2,str,nqp
  if(!INITPYWRAP) {printf("pycohere ERR0A: python.hoc not initialized properly\n") return nil}
  if(!nrnpython("from matplotlib.mlab import cohere")) {printf("pycohere ERR0B: could not import cohere from matplotlib.mlab!\n") return nil}  
  if(numarg()==0) {printf("pycohere(vec1,vec2,samplingrate)\n") return nil}
  v1=$o1 v2=$o2 sampr=$3 str=new String()
  {p.vjnk1=v1.to_python() p.vjnk1=p.numpy.array(p.vjnk1)}
  {p.vjnk2=v2.to_python() p.vjnk2=p.numpy.array(p.vjnk2)}
  sprint(str.s,"[Pxy,freqs]=cohere(vjnk1,vjnk2,Fs=%g)",sampr)
  nrnpython(str.s)
  nqp=new NQS("f","coh")
  nqp.v[0].from_python(p.freqs)
  nqp.v[1].from_python(p.Pxy)
  return nqp
}

//* pypca(matrix) - does PCA on input matrix and returns scores (projections onto PCs)
// rows of the matrix are observations, columns are 'features' or 'dimensions'
obfunc pypca () { local r,c,a localobj inm,inmT,vin,vout,str,mout
  if(!INITPYWRAP) {printf("pypca ERR0A: python.hoc not initialized properly\n") return nil}
  if(!nrnpython("from princomp import PCA")) {printf("pypca ERR0B: could not import PCA!\n") return nil}  
  if(!nrnpython("import numpy as np")){printf("pypca ERR0C: could not import numpy as np!\n") return nil}
  str=new String2()
  if(numarg()<1) {printf("pypca(Vector,rows,cols)\n") return nil}
  a=allocvecs(vin,vout)
  {inm=$o1 r=inm.nrow c=inm.ncol}
  inmT = inm.transpose() // transpose since to_vector goes in column ordering
  {vin.resize(r*c) inmT.to_vector(vin)}
  p.vjnk = vin.to_python() // convert to python format
  sprint(str.s,"vjnk=np.resize(vjnk,(%d,%d))",r,c)
  if(!nrnpython(str.s)){printf("pypca ERR0D: could not run %s\n",str.s) dealloc(a) return nil}
  if(!nrnpython("mypca=PCA(vjnk)")){printf("pypca ERR0E: could not run PCA\n") dealloc(a) return nil}
  if(!nrnpython("score=mypca.Y")){printf("pypca ERR0F: could not set scores\n") dealloc(a) return nil}
  sprint(str.s,"score=np.resize(score,(%d,1))",r*c)
  if(!nrnpython(str.s)){printf("pypca ERR0E: could not run %s\n",str.s) dealloc(a) return nil}
  vout.from_python(p.score) // convert to a hoc Vector  
  mout=new Matrix(c,r)//output as a matrix. NB: c,r are reversed from original for following transpose
  mout.from_vector(vout)//from_vector uses column ordering
  mout = mout.transpose()//so need to transpose
  dealloc(a)
  return mout
}

//* pyspecck(vec,sampr[,maxf,win]) - call ck's spectrogram.py
// vec = time-series. sampr = sampling rate (Hz).
// maxf = max frequency. win = window size (seconds) for specgram chunks
// system call to spectrogram.py file to display a spectrogram, writes temp
// file and then deletes it...
func pyspecck () { local i,sampr,maxf,win localobj fp,vec,str
  vec=$o1 sampr=$2
  if(numarg()>2)maxf=$3 else maxf=sampr/2
  if(numarg()>3)win=$4 else win=1
  str=new String2()
  fp=new File()
  if(!fp.mktemp()){printf("pyspecck ERR0: couldn't make temp file!\n") return 0}
  str.s=fp.getname()
  fp.wopen(str.s)
  for i=0,vec.size-1 fp.printf("%g\n",vec.x(i))
  fp.close()  
  sprint(str.t,"/usr/site/nrniv/local/python/spectrogram.py %s %g %g %g",str.s,sampr,maxf,win)
  print str.t
  system(str.t)
  fp.unlink()
  return 1
}

//* pykstest(vec1,vec2) - perform a two-sample, two-sided kolmogorov-smirnov test
// and return the p-value. kstest checks if values in vec1,vec2 come from same distribution (null hypothesis)
// returns -1 on failure. uses scipy.stats.ks_2samp function
func pykstest () { localobj v1,v2
  if(!INITPYWRAP) {printf("pykstest ERR0A: python.hoc not initialized properly\n") return -1}
  {v1=$o1 v2=$o2}
  if(!nrnpython("from scipy.stats import ks_2samp")) return -1
  {p.v1=v1.to_python() p.v2=v2.to_python()}
  if(!nrnpython("(D,pval)=ks_2samp(v1,v2)")) return -1
  return p.pval  
}