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 V1 pyramidal corticothalamic L6 cell; Neocortex U1 pyramidal intratelencephalic L2-6 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 pyramidal corticothalamic L6 cell; Neocortex V1 interneuron basket PV cell; Neocortex U1 pyramidal intratelencephalic L2-6 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: misc.mod,v 1.24 2011/10/14 15:00:26 samn Exp $

COMMENT
Misc. routines:
sassign() // assign a string from system
dassign()// assign a double
nokill() // chatch SIGHUP
prtime() // gives date/time
fspitchar(c,file) // sends single char to a file
spitchar(c)       // sends single char to stdout: eg c=1 => ^A
file_exist(file) // returns 1 if filename exists
hocgetc(file) // get single char from a file

  Note that with a SUFFIX equal to "nothing" these functions do not
have a suffix in hoc.  Thus to call sassign() in hoc use simply type
"sassign()" <- without the quotes.

    file_exist(filename)
        - returns 1 if filename exists

    sassign()  (string assign, written by Bill Lytton)
        - This routine is used to set a string in Hoc to something that has
          been returned by a system call.  sassign("name","shell_call ...")
          will produce a file called "sassign" in the cwd that will contain
          a hoc call that sets string 'name' to the result of shell_call 
          which should be a string.
        
    dassign()  (double assign, written and used by Bill Lytton)
        - This routine is used to set a variable in Hoc to something that has
          been returned by a system call.  sassign("name","shell_call ...")
          will produce a file called "dassign" in the cwd that will contain
          a hoc call that sets variable 'name' to the result of shell_call 
          which should be a number.

ENDCOMMENT
                           
INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}

NEURON {
    SUFFIX nothing
}

VERBATIM
#include <unistd.h>     /* F_OK     */
#include <errno.h>      /* errno    */
#include <signal.h>
#include <sys/types.h>         /* MUST REMEMBER THIS */
#include <time.h>
#include <stdio.h>
#include <limits.h>
extern int hoc_is_tempobj(int narg);
ENDVERBATIM

:* FUNCTION file_exist()
FUNCTION file_exist() {
VERBATIM
    /* Returns TRUE if file exists, if file not exist the need to reset
       errno else will get a nrnoc error.  Seems to be a problem even
       if I don't include <errno.h> */

    char *gargstr(), *filename;

    filename = gargstr(1);

    if (*filename && !access(filename, F_OK)) {
        _lfile_exist = 1;

    } else {
        /* Errno set to 2 when file not found */
        errno = 0;

        _lfile_exist = 0;
    }
ENDVERBATIM
}

FUNCTION istmpobj () {
VERBATIM
  _listmpobj=hoc_is_tempobj_arg(1);
ENDVERBATIM  
}

:* PROCEDURE sassign()
FUNCTION sassign() {
VERBATIM
    FILE *pipein;
    char string[BUFSIZ], **strname, *syscall;
    char** hoc_pgargstr();

    strname = hoc_pgargstr(1);
    syscall = gargstr(2);

    if( !(pipein = popen(syscall, "r"))) {
        fprintf(stderr,"System call failed\n");
        return 0; 
    }
    
    if (fgets(string,BUFSIZ,pipein) == NULL) {
        fprintf(stderr,"System call did not return a string\n");
        pclose(pipein); return 0;
    }

    /*  assign_hoc_str(strname, string, 0); */
    hoc_assign_str(strname, string);

    pclose(pipein);
    errno = 0;
    return 0;
ENDVERBATIM
}

:* PROCEDURE dassign() 
FUNCTION dassign() {
VERBATIM
    FILE *pipein, *outfile;
    char *strname, *syscall;
    double num;

    strname = gargstr(1);
    syscall = gargstr(2);

    if ( !(outfile = fopen("dassign","w"))) {
        fprintf(stderr,"Can't open output file dassign\n");
        return 0; 
    }

    if( !(pipein = popen(syscall, "r"))) {
        fprintf(stderr,"System call failed\n");
        fclose(outfile); return 0; 
    }
    
    if (fscanf(pipein,"%lf",&num) != 1) {
        fprintf(stderr,"System call did not return a number\n");
        fclose(outfile); pclose(pipein); return 0; 
    }

    fprintf(outfile,"%s=%g\n",strname,num);
    fprintf(outfile,"system(\"rm dassign\")\n");

    fclose(outfile); pclose(pipein);
    errno = 0;
    return 0;
ENDVERBATIM
}

:* PROCEDURE nokill() 
: nohup
PROCEDURE nokill() {
VERBATIM
  signal(SIGHUP, SIG_IGN);
ENDVERBATIM
}

:* FUNCTION prtime()
FUNCTION prtime () {
VERBATIM
_lprtime = clock();
ENDVERBATIM
}

:* FUNCTION now ()
FUNCTION now () {
VERBATIM
  _lnow = time((time_t*)0);
  _lnow -= (12784) * 24*60*60; // time from the Epoch to 01/01/05
ENDVERBATIM
}

:* FUNCTION sleepfor (seconds[,nanoseconds])
: returns 0 on success, -1 on failure, nanosecond arg should be < 1 second
FUNCTION sleepfor (sec) {
VERBATIM
  struct timespec ts;
  ts.tv_sec = (time_t)_lsec;
  ts.tv_nsec = ifarg(2)?(long)*getarg(2):(long)0;
  return (double) nanosleep(&ts,(struct timespec*)0);
ENDVERBATIM
}

:* PROCEDURE spitchar
PROCEDURE spitchar(c) {
VERBATIM
{	
  printf("%c", (int)_lc);
}
ENDVERBATIM
}

:* PROCEDURE spitchar
VERBATIM
static char *pmlc;
ENDVERBATIM

PROCEDURE mymalloc(sz) {
VERBATIM
{ 
  size_t x,y;
  x=(size_t)_lsz;
  pmlc=(char *)malloc(x);
  printf("Did %ld: %x\n",x,pmlc);
  y=(unsigned int)_lsz-1;
  pmlc[y]=(char)97;
  printf("WRITE/READ 'a': "); 
  printf("%c\n",pmlc[y]);
  if (ifarg(2)) free(pmlc); else printf("Use unmalloc() to free memory\n");
}
ENDVERBATIM
}

PROCEDURE unmalloc() {
VERBATIM
  free(pmlc);
ENDVERBATIM
}

:* FUNCTION hocgetc
FUNCTION hocgetc() {
VERBATIM
{	
  FILE* f, *hoc_obj_file_arg();
  f = hoc_obj_file_arg(1);
  _lhocgetc = (double)getc(f);
}
ENDVERBATIM
}

PROCEDURE pwd() {
  VERBATIM
  {char cwd[1000],cmd[1200];
  getcwd(cwd, 1000);
  sprintf(cmd, "execute1(\"strdef cwd\")\n");         hoc_oc(cmd);
  sprintf(cmd, "execute1(\"cwd=\\\"%s\\\"\")\n",cwd); hoc_oc(cmd);
  }
  ENDVERBATIM
}

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