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

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" ... 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. ..."
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]; Dura-Bernal, Salvador [salvadordura at];
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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km.mod *
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misc.mod *
MyExp2SynBB.mod *
stats.mod *
vecst.mod * *
declist.hoc *
decnqs.hoc *
decvec.hoc *
default.hoc *
drline.hoc * *
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// $Id: misc.h,v 1.38 2011/11/02 15:26:48 billl Exp $

#include <stdlib.h>
#include <math.h>
#include <limits.h> /* contains LONG_MAX */
#include <time.h>
#include <sys/time.h> 
#include <float.h>
#include <pthread.h>

#if !defined(t)
  #define _pval pval

typedef struct LISTVEC {
  int isz;
  Object* pL;
  double** pv;
  unsigned int* plen;
  unsigned int* pbuflen;
} ListVec;

typedef struct BVEC {
 int size;
 int bufsize;
 short *x;
 Object* o;
} bvec;

#define BYTEHEADER int _II__;  char *_IN__; char _OUT__[16]; int BYTESWAP_FLAG=0;
#define BYTESWAP(_X__,_TYPE__) \
    if (BYTESWAP_FLAG == 1) { \
    _IN__ = (char *) &(_X__); \
    for (_II__=0;_II__<sizeof(_TYPE__);_II__++) { \
        _OUT__[_II__] = _IN__[sizeof(_TYPE__)-_II__-1]; } \
    (_X__) = *((_TYPE__ *) &_OUT__); \

#define UNCODE(_X_,_J_,_Y_) {(_Y_)=floor((_X_)/sc[(_J_)])/sc[4]; \
#define MIN(X,Y) ((X) < (Y) ? (X) : (Y))
#define MAX(X,Y) ((X) > (Y) ? (X) : (Y))

//square root of 2 * PI
#define SQRT2PI 2.5066282746310002416
//ln(2), base e log of 2
#define LG2 0.69314718055994530941723212145818
#define VRRY 200
#define ISVEC(_OB__) (strncmp(hoc_object_name(_OB__),"Vector",6)==0)
#define dmaxuint 4294967295. // for 32 bits

// Andre Fentons cast designations
typedef unsigned char   ui1;    /* one byte unsigned integer */
typedef char        si1;    /* one byte signed integer */
typedef unsigned short  ui2;    /* two byte unsigned integer */
typedef short       si2;    /* two byte signed integer */
typedef unsigned int    ui4;    /* four byte unsigned integer */ 
typedef int     si4;    /* four byte signed integer */ 
typedef float       sf4;    /* four byte signed floating point number */ 
typedef double      sf8;    /* eight byte signed floating point number */ 


extern double *vector_newsize();
extern unsigned int  dcrsz;
extern double       *dcr;
extern double       *dcrset(int);
extern unsigned int  scrsz;
extern unsigned int *scr;
extern unsigned int *scrset(int);
extern unsigned int  iscrsz;
extern int *iscr;
extern int *iscrset(int);
extern double BVBASE;
extern double* hoc_pgetarg();
extern void hoc_notify_iv();
extern double hoc_call_func(Symbol*, int narg);
extern FILE* hoc_obj_file_arg(int narg);
extern Object** hoc_objgetarg();
char *gargstr();
char** hoc_pgargstr();
extern void vector_resize();
extern int vector_instance_px();
extern void* vector_arg();
extern double* vector_vec();
extern int vector_buffer_size(void*);
extern double hoc_epsilon;
extern int stoprun;
extern void set_seed();
extern void dshuffle(double* x,int nx);
extern void mcell_ran4_init(u_int32_t);
extern double mcell_ran4(u_int32_t *idx1, double *x, unsigned int n, double range);
extern int nrn_mlh_gsort();
extern int ivoc_list_count(Object*);
extern Object* ivoc_list_item(Object*, int);
extern int list_vector_px2();
extern int hoc_is_double_arg(int narg);
extern int hoc_is_str_arg(int narg);
extern int hoc_is_object_arg(int narg);
extern int hoc_is_pdouble_arg(int narg);
extern Symbol *hoc_get_symbol(char *);
extern Symbol *hoc_lookup(const char*);
extern Point_process* ob2pntproc(Object*);

extern char* hoc_object_name(Object*);
extern int cmpdfn();
extern int openvec(int, double **);
int list_vector_px();
double *list_vector_resize();
static void hxe() { hoc_execerror("",0); }
extern void FreeListVec(ListVec** pp);
extern ListVec* AllocListVec(Object* p);
extern ListVec* AllocILV(Object*, int, double *);
void FillListVec(ListVec* p,double dval);
void ListVecResize(ListVec* p,int newsz);
extern short *nrn_artcell_qindex_;
extern double nrn_event_queue_stats(double*);
extern void clear_event_queue();

static double sc[6];
static FILE*  testout;

//* in vecst.mod
extern int** getint2D(int rows,int cols);
extern void freeint2D(int*** ppp,int rows);
extern double** getdouble2D(int rows,int cols);
extern void freedouble2D(double*** ppp,int rows);
extern double ismono1 (double *x, int n, int flag);

//* in stats.mod
double kcorfast(double* input1, double* input2, double* i1d , double* i2d,int n,double* ps);
double Rktau (double* x, double* y, int n); // R version
double kcorfast (double* input1, double* input2, double* i1d , double* i2d,int n,double* ps);

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