Linear vs non-linear integration in CA1 oblique dendrites (Gómez González et al. 2011)

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Accession:144450
The hippocampus in well known for its role in learning and memory processes. The CA1 region is the output of the hippocampal formation and pyramidal neurons in this region are the elementary units responsible for the processing and transfer of information to the cortex. Using this detailed single neuron model, it is investigated the conditions under which individual CA1 pyramidal neurons process incoming information in a complex (non-linear) as opposed to a passive (linear) manner. This detailed compartmental model of a CA1 pyramidal neuron is based on one described previously (Poirazi, 2003). The model was adapted to five different reconstructed morphologies for this study, and slightly modified to fit the experimental data of (Losonczy, 2006), and to incorporate evidence in pyramidal neurons for the non-saturation of NMDA receptor-mediated conductances by single glutamate pulses. We first replicate the main findings of (Losonczy, 2006), including the very brief window for nonlinear integration using single-pulse stimuli. We then show that double-pulse stimuli increase a CA1 pyramidal neuron’s tolerance for input asynchrony by at last an order of magnitude. Therefore, it is shown using this model, that the time window for nonlinear integration is extended by more than an order of magnitude when inputs are short bursts as opposed to single spikes.
Reference:
1 . Gómez González JF, Mel BW, Poirazi P (2011) Distinguishing Linear vs. Non-Linear Integration in CA1 Radial Oblique Dendrites: It's about Time. Front Comput Neurosci 5:44 [PubMed]
Citations  Citation Browser
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism:
Cell Type(s): Hippocampus CA1 pyramidal GLU cell;
Channel(s): I Na,p; I CAN; I Sodium; I Calcium; I Potassium; I_AHP;
Gap Junctions:
Receptor(s): NMDA;
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Active Dendrites; Detailed Neuronal Models; Synaptic Integration;
Implementer(s):
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; NMDA; I Na,p; I CAN; I Sodium; I Calcium; I Potassium; I_AHP;
/* Created by Language version: 6.0.2 */
/* NOT VECTORIZED */
#include <stdio.h>
#include <math.h>
#include "scoplib.h"
#undef PI
 
#include "md1redef.h"
#include "section.h"
#include "nrnoc_ml.h"
#include "md2redef.h"

#if METHOD3
extern int _method3;
#endif

#undef exp
#define exp hoc_Exp
extern double hoc_Exp();
 	/*SUPPRESS 761*/
	/*SUPPRESS 762*/
	/*SUPPRESS 763*/
	/*SUPPRESS 765*/
	 extern double *getarg();
 static double *_p; static Datum *_ppvar;
 
#define delta_t dt
#define iglu _p[0]
#define g _p[1]
#define gmax _p[2]
#define Ron _p[3]
#define Roff _p[4]
#define synon _p[5]
#define DRon _p[6]
#define DRoff _p[7]
#define _g _p[8]
#define _tsav _p[9]
#define _nd_area  *_ppvar[0].pval
 
#if MAC
#if !defined(v)
#define v _mlhv
#endif
#if !defined(h)
#define h _mlhh
#endif
#endif
 static int hoc_nrnpointerindex =  -1;
 /* external NEURON variables */
 extern double dt;
 extern double t;
 /* declaration of user functions */
 static int _mechtype;
extern int nrn_get_mechtype();
 extern Prop* nrn_point_prop_;
 static int _pointtype;
 static void* _hoc_create_pnt(_ho) Object* _ho; { void* create_point_process();
 return create_point_process(_pointtype, _ho);
}
 static void _hoc_destroy_pnt();
 static double _hoc_loc_pnt(_vptr) void* _vptr; {double loc_point_process();
 return loc_point_process(_pointtype, _vptr);
}
 static double _hoc_has_loc(_vptr) void* _vptr; {double has_loc_point();
 return has_loc_point(_vptr);
}
 static double _hoc_get_loc_pnt(_vptr)void* _vptr; {
 double get_loc_point_process(); return (get_loc_point_process(_vptr));
}
 static _hoc_setdata(_vptr) void* _vptr; { Prop* _prop;
 _prop = ((Point_process*)_vptr)->_prop;
 _p = _prop->param; _ppvar = _prop->dparam;
 }
 /* connect user functions to hoc names */
 static IntFunc hoc_intfunc[] = {
 0,0
};
 static struct Member_func {
	char* _name; double (*_member)();} _member_func[] = {
 "loc", _hoc_loc_pnt,
 "has_loc", _hoc_has_loc,
 "get_loc", _hoc_get_loc_pnt,
 0, 0
};
 /* declare global and static user variables */
#define Alpha Alpha_GLU
 double Alpha = 0.94;
#define Beta Beta_GLU
 double Beta = 0.3;
#define Cmax Cmax_GLU
 double Cmax = 1;
#define Cdur Cdur_GLU
 double Cdur = 0.3;
#define Erev Erev_GLU
 double Erev = 0;
#define Rtau Rtau_GLU
 double Rtau = 0;
#define Rinf Rinf_GLU
 double Rinf = 0;
 /* some parameters have upper and lower limits */
 static HocParmLimits _hoc_parm_limits[] = {
 0,0,0
};
 static HocParmUnits _hoc_parm_units[] = {
 "Cmax_GLU", "mM",
 "Alpha_GLU", "/ms",
 "Erev_GLU", "mV",
 "Rtau_GLU", "ms",
 "iglu", "nA",
 "g", "umho",
 0,0
};
 static double Roff0 = 0;
 static double Ron0 = 0;
 static double v = 0;
 /* connect global user variables to hoc */
 static DoubScal hoc_scdoub[] = {
 "Cmax_GLU", &Cmax,
 "Cdur_GLU", &Cdur,
 "Alpha_GLU", &Alpha,
 "Beta_GLU", &Beta,
 "Erev_GLU", &Erev,
 "Rinf_GLU", &Rinf,
 "Rtau_GLU", &Rtau,
 0,0
};
 static DoubVec hoc_vdoub[] = {
 0,0,0
};
 static double _sav_indep;
 static nrn_alloc(), nrn_init(), nrn_state();
 static nrn_cur(), nrn_jacob();
 static void _hoc_destroy_pnt(_vptr) void* _vptr; {
   destroy_point_process(_vptr);
}
 
static int _ode_count(), _ode_map(), _ode_spec(), _ode_matsol();
extern int nrn_cvode_;
 
#define _cvode_ieq _ppvar[3]._i
 /* connect range variables in _p that hoc is supposed to know about */
 static char *_mechanism[] = {
 "6.0.2",
"GLU",
 0,
 "iglu",
 "g",
 "gmax",
 0,
 "Ron",
 "Roff",
 0,
 0};
 
static nrn_alloc(_prop)
	Prop *_prop;
{
	Prop *prop_ion, *need_memb();
	double *_p; Datum *_ppvar;
  if (nrn_point_prop_) {
	_p = nrn_point_prop_->param;
	_ppvar = nrn_point_prop_->dparam;
 }else{
 	_p = nrn_prop_data_alloc(_mechtype, 10);
 	/*initialize range parameters*/
  }
 	_prop->param = _p;
 	_prop->param_size = 10;
  if (!nrn_point_prop_) {
 	_ppvar = nrn_prop_datum_alloc(_mechtype, 4);
  }
 	_prop->dparam = _ppvar;
 	/*connect ionic variables to this model*/
 
}
 static _initlists();
  /* some states have an absolute tolerance */
 static Symbol** _atollist;
 static HocStateTolerance _hoc_state_tol[] = {
 0,0
};
 
#define _tqitem &(_ppvar[2]._pvoid)
 static _net_receive();
 typedef (*_Pfrv)();
 extern _Pfrv* pnt_receive;
 extern short* pnt_receive_size;
 _ampa_reg() {
	int _vectorized = 0;
  _initlists();
 	_pointtype = point_register_mech(_mechanism,
	 nrn_alloc,nrn_cur, nrn_jacob, nrn_state, nrn_init,
	 hoc_nrnpointerindex,
	 _hoc_create_pnt, _hoc_destroy_pnt, _member_func,
	 _vectorized);
 _mechtype = nrn_get_mechtype(_mechanism[1]);
  hoc_register_dparam_size(_mechtype, 4);
 	hoc_register_cvode(_mechtype, _ode_count, _ode_map, _ode_spec, _ode_matsol);
 	hoc_register_tolerance(_mechtype, _hoc_state_tol, &_atollist);
 pnt_receive[_mechtype] = _net_receive;
 pnt_receive_size[_mechtype] = 5;
 	hoc_register_var(hoc_scdoub, hoc_vdoub, hoc_intfunc);
 	ivoc_help("help ?1 GLU /home/jg/ModelosNeuron/ProgramsNeuronCA1_JG/CleanVersion_CA1_JG_15Mar09/mechanism/x86_64/ampa.mod\n");
 hoc_register_limits(_mechtype, _hoc_parm_limits);
 hoc_register_units(_mechtype, _hoc_parm_units);
 }
static int _reset;
static char *modelname = "simple AMPA receptors";

static int error;
static int _ninits = 0;
static int _match_recurse=1;
static _modl_cleanup(){ _match_recurse=1;}
 
static int _ode_spec1(), _ode_matsol1();
 extern int state_discon_flag_;
 static int _slist1[2], _dlist1[2];
 static int release();
 
/*CVODE*/
 static int _ode_spec1 () {_reset=0;
 {
   DRon = ( synon * Rinf - Ron ) / Rtau ;
   DRoff = - Beta * Roff ;
   }
 return _reset;
}
 static int _ode_matsol1() {
 DRon = DRon  / (1. - dt*( ( ( ( - 1.0 ) ) ) / Rtau )) ;
 DRoff = DRoff  / (1. - dt*( (- Beta)*(1.0) )) ;
}
 /*END CVODE*/
 static int release () {_reset=0;
 {
    Ron = Ron + (1. - exp(dt*(( ( ( - 1.0 ) ) ) / Rtau)))*(- ( ( ( (synon)*(Rinf) ) ) / Rtau ) / ( ( ( ( - 1.0) ) ) / Rtau ) - Ron) ;
    Roff = Roff + (1. - exp(dt*((- Beta)*(1.0))))*(- ( 0.0 ) / ( (- Beta)*(1.0) ) - Roff) ;
   }
  return 0;
}
 
static _net_receive (_pnt, _args, _lflag) Point_process* _pnt; double* _args; double _lflag; 
{ _p = _pnt->_prop->param; _ppvar = _pnt->_prop->dparam;
  if (_tsav > t){ extern char* hoc_object_name(); hoc_execerror(hoc_object_name(_pnt->ob), ":Event arrived out of order. Must call ParallelContext.set_maxstep AFTER assigning minimum NetCon.delay");}
 _tsav = t;   if (_lflag == 1. ) {*(_tqitem) = 0;}
 {
   if ( _lflag  == 0.0 ) {
     _args[2] = _args[2] + 1.0 ;
     if (  ! _args[1] ) {
       _args[3] = _args[3] * exp ( - Beta * ( t - _args[4] ) ) ;
       _args[4] = t ;
       _args[1] = 1.0 ;
       synon = synon + _args[0] ;
       state_discontinuity ( _cvode_ieq + 0, & Ron , Ron + _args[3] ) ;
       state_discontinuity ( _cvode_ieq + 1, & Roff , Roff - _args[3] ) ;
       }
     net_send ( _tqitem, _args, _pnt, Cdur , _args[2] ) ;
     }
   if ( _lflag  == _args[2] ) {
     _args[3] = _args[0] * Rinf + ( _args[3] - _args[0] * Rinf ) * exp ( - ( t - _args[4] ) / Rtau ) ;
     _args[4] = t ;
     synon = synon - _args[0] ;
     state_discontinuity ( _cvode_ieq + 0, & Ron , Ron - _args[3] ) ;
     state_discontinuity ( _cvode_ieq + 1, & Roff , Roff + _args[3] ) ;
     _args[1] = 0.0 ;
     }
   gmax = _args[0] ;
   } }
 
static int _ode_count(_type) int _type;{ return 2;}
 
static int _ode_spec(_nd, _pp, _ppd) Node* _nd; double* _pp; Datum* _ppd; {
	_p = _pp; _ppvar = _ppd; v = NODEV(_nd);
  _ode_spec1();
 }
 
static int _ode_map(_ieq, _pv, _pvdot, _pp, _ppd, _atol, _type) int _ieq, _type; double** _pv, **_pvdot, *_pp, *_atol; Datum* _ppd; {
	int _i; _p = _pp; _ppvar = _ppd;
	_cvode_ieq = _ieq;
	for (_i=0; _i < 2; ++_i) {
		_pv[_i] = _pp + _slist1[_i];  _pvdot[_i] = _pp + _dlist1[_i];
		_cvode_abstol(_atollist, _atol, _i);
	}
 }
 
static int _ode_matsol(_nd, _pp, _ppd) Node* _nd; double* _pp; Datum* _ppd; {
	_p = _pp; _ppvar = _ppd; v = NODEV(_nd);
 _ode_matsol1();
 }

static initmodel() {
  int _i; double _save;_ninits++;
 _save = t;
 t = 0.0;
{
  Roff = Roff0;
  Ron = Ron0;
 {
   Rinf = Cmax * Alpha / ( Cmax * Alpha + Beta ) ;
   Rtau = 1.0 / ( ( Alpha * Cmax ) + Beta ) ;
   synon = 0.0 ;
   }
  _sav_indep = t; t = _save;

}
}

static nrn_init(_ml, _type) _Memb_list* _ml; int _type;{
Node *_nd; double _v; int* _ni; int _iml, _cntml;
#if CACHEVEC
    _ni = _ml->_nodeindices;
#endif
_cntml = _ml->_nodecount;
for (_iml = 0; _iml < _cntml; ++_iml) {
 _p = _ml->_data[_iml]; _ppvar = _ml->_pdata[_iml];
 _tsav = -1e20;
#if CACHEVEC
  if (use_cachevec) {
    _v = VEC_V(_ni[_iml]);
  }else
#endif
  {
    _nd = _ml->_nodelist[_iml];
    _v = NODEV(_nd);
  }
 v = _v;
 initmodel();
}}

static double _nrn_current(_v) double _v;{double _current=0.;v=_v;{ {
   g = ( Ron + Roff ) * 1.0 ;
   iglu = g * ( v - Erev ) ;
   }
 _current += iglu;

} return _current;
}

static nrn_cur(_ml, _type) _Memb_list* _ml; int _type;{
Node *_nd; int* _ni; double _rhs, _v; int _iml, _cntml;
#if CACHEVEC
    _ni = _ml->_nodeindices;
#endif
_cntml = _ml->_nodecount;
for (_iml = 0; _iml < _cntml; ++_iml) {
 _p = _ml->_data[_iml]; _ppvar = _ml->_pdata[_iml];
#if CACHEVEC
  if (use_cachevec) {
    _v = VEC_V(_ni[_iml]);
  }else
#endif
  {
    _nd = _ml->_nodelist[_iml];
    _v = NODEV(_nd);
  }
 _g = _nrn_current(_v + .001);
 	{ state_discon_flag_ = 1; _rhs = _nrn_current(_v); state_discon_flag_ = 0;
 	}
 _g = (_g - _rhs)/.001;
 _g *=  1.e2/(_nd_area);
 _rhs *= 1.e2/(_nd_area);
#if CACHEVEC
  if (use_cachevec) {
	VEC_RHS(_ni[_iml]) -= _rhs;
  }else
#endif
  {
	NODERHS(_nd) -= _rhs;
  }
 
}}

static nrn_jacob(_ml, _type) _Memb_list* _ml; int _type;{
Node *_nd; int* _ni; int _iml, _cntml;
#if CACHEVEC
    _ni = _ml->_nodeindices;
#endif
_cntml = _ml->_nodecount;
for (_iml = 0; _iml < _cntml; ++_iml) {
 _p = _ml->_data[_iml];
#if CACHEVEC
  if (use_cachevec) {
	VEC_D(_ni[_iml]) += _g;
  }else
#endif
  {
     _nd = _ml->_nodelist[_iml];
	NODED(_nd) += _g;
  }
 
}}

static nrn_state(_ml, _type) _Memb_list* _ml; int _type;{
 double _break, _save;
Node *_nd; double _v; int* _ni; int _iml, _cntml;
#if CACHEVEC
    _ni = _ml->_nodeindices;
#endif
_cntml = _ml->_nodecount;
for (_iml = 0; _iml < _cntml; ++_iml) {
 _p = _ml->_data[_iml]; _ppvar = _ml->_pdata[_iml];
 _nd = _ml->_nodelist[_iml];
#if CACHEVEC
  if (use_cachevec) {
    _v = VEC_V(_ni[_iml]);
  }else
#endif
  {
    _nd = _ml->_nodelist[_iml];
    _v = NODEV(_nd);
  }
 _break = t + .5*dt; _save = t; delta_t = dt;
 v=_v;
{
 { {
 for (; t < _break; t += delta_t) {
 error =  release();
 if(error){fprintf(stderr,"at line 94 in file ampa.mod:\n	SOLVE release METHOD cnexp\n"); nrn_complain(_p); abort_run(error);}
 
}}
 t = _save;
 }}}

}

static terminal(){}

static _initlists() {
 int _i; static int _first = 1;
  if (!_first) return;
 _slist1[0] = &(Ron) - _p;  _dlist1[0] = &(DRon) - _p;
 _slist1[1] = &(Roff) - _p;  _dlist1[1] = &(DRoff) - _p;
_first = 0;
}