Glutamate mediated dendritic and somatic plateau potentials in cortical L5 pyr cells (Gao et al '20)

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Accession:249705
Our model was built on a reconstructed Layer 5 pyramidal neuron of the rat medial prefrontal cortex, and constrained by 4 sets of experimental data: (i) voltage waveforms obtained at the site of the glutamatergic input in distal basal dendrite, including initial sodium spikelet, fast rise, plateau phase and abrupt collapse of the plateau; (ii) a family of voltage traces describing dendritic membrane responses to gradually increasing intensity of glutamatergic stimulation; (iii) voltage waveforms of backpropagating action potentials in basal dendrites (Antic, 2003); and (iv) the change of backpropagating action potential amplitude in response to drugs that block Na+ or K+ channels (Acker and Antic, 2009). Both, synaptic AMPA/NMDA and extrasynaptic NMDA inputs were placed on basal dendrites to model the induction of local regenerative potentials termed "glutamate-mediated dendritic plateau potentials". The active properties of the cell were tuned to match the voltage waveform, amplitude and duration of experimentally observed plateau potentials. The effects of input location, receptor conductance, channel properties and membrane time constant during plateau were explored. The new model predicted that during dendritic plateau potential the somatic membrane time constant is reduced. This and other model predictions were then tested in real neurons. Overall, the results support our theoretical framework that dendritic plateau potentials bring neuronal cell body into a depolarized state ("UP state"), which lasts 200 - 500 ms, or more. Plateau potentials profoundly change neuronal state -- a plateau potential triggered in one basal dendrite depolarizes the soma and shortens membrane time constant, making the cell more susceptible to action potential firing triggered by other afferent inputs. Plateau potentials may allow cortical pyramidal neurons to tune into ongoing network activity and potentially enable synchronized firing, to form active neural ensembles.
Reference:
1 . Gao PP, Graham JW, Zhou WL, Jang J, Angulo SL, Dura-Bernal S, Hines ML, Lytton W, Antic SD (2020) Local Glutamate-Mediated Dendritic Plateau Potentials Change the State of the Cortical Pyramidal Neuron. J Neurophysiol [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Dendrite; Neuron or other electrically excitable cell;
Brain Region(s)/Organism: Prefrontal cortex (PFC); Neocortex;
Cell Type(s): Neocortex L5/6 pyramidal GLU cell;
Channel(s): I A; I K; I h; I K,Ca;
Gap Junctions:
Receptor(s): Glutamate; NMDA;
Gene(s):
Transmitter(s): Glutamate;
Simulation Environment: NEURON; Python;
Model Concept(s): Action Potentials; Active Dendrites; Calcium dynamics; Axonal Action Potentials; Dendritic Bistability; Detailed Neuronal Models; Membrane Properties; Synaptic Integration;
Implementer(s): Antic, Srdjan [antic at neuron.uchc.edu]; Gao, Peng [peng at uchc.edu];
Search NeuronDB for information about:  Neocortex L5/6 pyramidal GLU cell; NMDA; Glutamate; I A; I K; I h; I K,Ca; Glutamate; 
/* Created by Language version: 7.5.0 */
/* NOT VECTORIZED */
#define NRN_VECTORIZED 0
#include <stdio.h>
#include <stdlib.h>
#include <math.h>
#include "scoplib_ansi.h"
#undef PI
#define nil 0
#include "md1redef.h"
#include "section.h"
#include "nrniv_mf.h"
#include "md2redef.h"
 
#if METHOD3
extern int _method3;
#endif

#if !NRNGPU
#undef exp
#define exp hoc_Exp
extern double hoc_Exp(double);
#endif
 
#define nrn_init _nrn_init__GABAa
#define _nrn_initial _nrn_initial__GABAa
#define nrn_cur _nrn_cur__GABAa
#define _nrn_current _nrn_current__GABAa
#define nrn_jacob _nrn_jacob__GABAa
#define nrn_state _nrn_state__GABAa
#define _net_receive _net_receive__GABAa 
#define release release__GABAa 
 
#define _threadargscomma_ /**/
#define _threadargsprotocomma_ /**/
#define _threadargs_ /**/
#define _threadargsproto_ /**/
 	/*SUPPRESS 761*/
	/*SUPPRESS 762*/
	/*SUPPRESS 763*/
	/*SUPPRESS 765*/
	 extern double *getarg();
 static double *_p; static Datum *_ppvar;
 
#define t nrn_threads->_t
#define dt nrn_threads->_dt
#define i _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
 
#if defined(__cplusplus)
extern "C" {
#endif
 static int hoc_nrnpointerindex =  -1;
 /* external NEURON variables */
 /* declaration of user functions */
 static int _mechtype;
extern void _nrn_cacheloop_reg(int, int);
extern void hoc_register_prop_size(int, int, int);
extern void hoc_register_limits(int, HocParmLimits*);
extern void hoc_register_units(int, HocParmUnits*);
extern void nrn_promote(Prop*, int, int);
extern Memb_func* memb_func;
 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));
}
 extern void _nrn_setdata_reg(int, void(*)(Prop*));
 static void _setdata(Prop* _prop) {
 _p = _prop->param; _ppvar = _prop->dparam;
 }
 static void _hoc_setdata(void* _vptr) { Prop* _prop;
 _prop = ((Point_process*)_vptr)->_prop;
   _setdata(_prop);
 }
 /* connect user functions to hoc names */
 static VoidFunc hoc_intfunc[] = {
 0,0
};
 static Member_func _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_GABAa
 double Alpha = 5;
#define Beta Beta_GABAa
 double Beta = 0.18;
#define Cdur Cdur_GABAa
 double Cdur = 1;
#define Cmax Cmax_GABAa
 double Cmax = 1;
#define Erev Erev_GABAa
 double Erev = -80;
#define Rtau Rtau_GABAa
 double Rtau = 0;
#define Rinf Rinf_GABAa
 double Rinf = 0;
 /* some parameters have upper and lower limits */
 static HocParmLimits _hoc_parm_limits[] = {
 0,0,0
};
 static HocParmUnits _hoc_parm_units[] = {
 "Cmax_GABAa", "mM",
 "Cdur_GABAa", "ms",
 "Alpha_GABAa", "/ms",
 "Beta_GABAa", "/ms",
 "Erev_GABAa", "mV",
 "Rtau_GABAa", "ms",
 "i", "nA",
 "g", "umho",
 0,0
};
 static double Roff0 = 0;
 static double Ron0 = 0;
 static double delta_t = 0.01;
 static double v = 0;
 /* connect global user variables to hoc */
 static DoubScal hoc_scdoub[] = {
 "Cmax_GABAa", &Cmax_GABAa,
 "Cdur_GABAa", &Cdur_GABAa,
 "Alpha_GABAa", &Alpha_GABAa,
 "Beta_GABAa", &Beta_GABAa,
 "Erev_GABAa", &Erev_GABAa,
 "Rinf_GABAa", &Rinf_GABAa,
 "Rtau_GABAa", &Rtau_GABAa,
 0,0
};
 static DoubVec hoc_vdoub[] = {
 0,0,0
};
 static double _sav_indep;
 static void nrn_alloc(Prop*);
static void  nrn_init(_NrnThread*, _Memb_list*, int);
static void nrn_state(_NrnThread*, _Memb_list*, int);
 static void nrn_cur(_NrnThread*, _Memb_list*, int);
static void  nrn_jacob(_NrnThread*, _Memb_list*, int);
 static void _hoc_destroy_pnt(_vptr) void* _vptr; {
   destroy_point_process(_vptr);
}
 
static int _ode_count(int);
static void _ode_map(int, double**, double**, double*, Datum*, double*, int);
static void _ode_spec(_NrnThread*, _Memb_list*, int);
static void _ode_matsol(_NrnThread*, _Memb_list*, int);
 
#define _cvode_ieq _ppvar[3]._i
 static void _ode_matsol_instance1(_threadargsproto_);
 /* connect range variables in _p that hoc is supposed to know about */
 static const char *_mechanism[] = {
 "7.5.0",
"GABAa",
 0,
 "i",
 "g",
 "gmax",
 0,
 "Ron",
 "Roff",
 0,
 0};
 
extern Prop* need_memb(Symbol*);

static void nrn_alloc(Prop* _prop) {
	Prop *prop_ion;
	double *_p; Datum *_ppvar;
  if (nrn_point_prop_) {
	_prop->_alloc_seq = nrn_point_prop_->_alloc_seq;
	_p = nrn_point_prop_->param;
	_ppvar = nrn_point_prop_->dparam;
 }else{
 	_p = nrn_prop_data_alloc(_mechtype, 10, _prop);
 	/*initialize range parameters*/
  }
 	_prop->param = _p;
 	_prop->param_size = 10;
  if (!nrn_point_prop_) {
 	_ppvar = nrn_prop_datum_alloc(_mechtype, 4, _prop);
  }
 	_prop->dparam = _ppvar;
 	/*connect ionic variables to this model*/
 
}
 static void _initlists();
  /* some states have an absolute tolerance */
 static Symbol** _atollist;
 static HocStateTolerance _hoc_state_tol[] = {
 0,0
};
 
#define _tqitem &(_ppvar[2]._pvoid)
 static void _net_receive(Point_process*, double*, double);
 extern Symbol* hoc_lookup(const char*);
extern void _nrn_thread_reg(int, int, void(*)(Datum*));
extern void _nrn_thread_table_reg(int, void(*)(double*, Datum*, Datum*, _NrnThread*, int));
extern void hoc_register_tolerance(int, HocStateTolerance*, Symbol***);
extern void _cvode_abstol( Symbol**, double*, int);

 void _gabaa_reg() {
	int _vectorized = 0;
  _initlists();
 	_pointtype = point_register_mech(_mechanism,
	 nrn_alloc,nrn_cur, nrn_jacob, nrn_state, nrn_init,
	 hoc_nrnpointerindex, 0,
	 _hoc_create_pnt, _hoc_destroy_pnt, _member_func);
 _mechtype = nrn_get_mechtype(_mechanism[1]);
     _nrn_setdata_reg(_mechtype, _setdata);
  hoc_register_prop_size(_mechtype, 10, 4);
  hoc_register_dparam_semantics(_mechtype, 0, "area");
  hoc_register_dparam_semantics(_mechtype, 1, "pntproc");
  hoc_register_dparam_semantics(_mechtype, 2, "netsend");
  hoc_register_dparam_semantics(_mechtype, 3, "cvodeieq");
 	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 GABAa /Users/Penny/Dropbox/ModelDB/mod/x86_64/gabaa.mod\n");
 hoc_register_limits(_mechtype, _hoc_parm_limits);
 hoc_register_units(_mechtype, _hoc_parm_units);
 }
static int _reset;
static char *modelname = "minimal model of GABAa receptors";

static int error;
static int _ninits = 0;
static int _match_recurse=1;
static void _modl_cleanup(){ _match_recurse=1;}
 
static int _ode_spec1(_threadargsproto_);
/*static int _ode_matsol1(_threadargsproto_);*/
 static int _slist1[2], _dlist1[2];
 static int release(_threadargsproto_);
 
/*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 ) )) ;
  return 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 void _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] ;
           if (nrn_netrec_state_adjust && !cvode_active_){
    /* discon state adjustment for cnexp case (rate uses no local variable) */
    double __state = Ron;
    double __primary = (Ron + _args[3] ) - __state;
     __primary += ( 1. - exp( 0.5*dt*( ( ( ( - 1.0 ) ) ) / Rtau ) ) )*( - ( ( ( ( synon )*( Rinf ) ) ) / Rtau ) / ( ( ( ( - 1.0 ) ) ) / Rtau ) - __primary );
    Ron += __primary;
  } else {
 Ron = Ron + _args[3]  ;
         }
     if (nrn_netrec_state_adjust && !cvode_active_){
    /* discon state adjustment for cnexp case (rate uses no local variable) */
    double __state = Roff;
    double __primary = (Roff - _args[3] ) - __state;
     __primary += ( 1. - exp( 0.5*dt*( ( - Beta )*( 1.0 ) ) ) )*( - ( 0.0 ) / ( ( - Beta )*( 1.0 ) ) - __primary );
    Roff += __primary;
  } else {
 Roff = Roff - _args[3]  ;
         }
 }
     net_send ( _tqitem, _args, _pnt, t +  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] ;
         if (nrn_netrec_state_adjust && !cvode_active_){
    /* discon state adjustment for cnexp case (rate uses no local variable) */
    double __state = Ron;
    double __primary = (Ron - _args[3] ) - __state;
     __primary += ( 1. - exp( 0.5*dt*( ( ( ( - 1.0 ) ) ) / Rtau ) ) )*( - ( ( ( ( synon )*( Rinf ) ) ) / Rtau ) / ( ( ( ( - 1.0 ) ) ) / Rtau ) - __primary );
    Ron += __primary;
  } else {
 Ron = Ron - _args[3]  ;
       }
     if (nrn_netrec_state_adjust && !cvode_active_){
    /* discon state adjustment for cnexp case (rate uses no local variable) */
    double __state = Roff;
    double __primary = (Roff + _args[3] ) - __state;
     __primary += ( 1. - exp( 0.5*dt*( ( - Beta )*( 1.0 ) ) ) )*( - ( 0.0 ) / ( ( - Beta )*( 1.0 ) ) - __primary );
    Roff += __primary;
  } else {
 Roff = Roff + _args[3]  ;
       }
 _args[1] = 0.0 ;
     }
   gmax = _args[0] ;
   } }
 
static int _ode_count(int _type){ return 2;}
 
static void _ode_spec(_NrnThread* _nt, _Memb_list* _ml, int _type) {
   Datum* _thread;
   Node* _nd; double _v; int _iml, _cntml;
  _cntml = _ml->_nodecount;
  _thread = _ml->_thread;
  for (_iml = 0; _iml < _cntml; ++_iml) {
    _p = _ml->_data[_iml]; _ppvar = _ml->_pdata[_iml];
    _nd = _ml->_nodelist[_iml];
    v = NODEV(_nd);
     _ode_spec1 ();
 }}
 
static void _ode_map(int _ieq, double** _pv, double** _pvdot, double* _pp, Datum* _ppd, double* _atol, int _type) { 
 	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 void _ode_matsol_instance1(_threadargsproto_) {
 _ode_matsol1 ();
 }
 
static void _ode_matsol(_NrnThread* _nt, _Memb_list* _ml, int _type) {
   Datum* _thread;
   Node* _nd; double _v; int _iml, _cntml;
  _cntml = _ml->_nodecount;
  _thread = _ml->_thread;
  for (_iml = 0; _iml < _cntml; ++_iml) {
    _p = _ml->_data[_iml]; _ppvar = _ml->_pdata[_iml];
    _nd = _ml->_nodelist[_iml];
    v = NODEV(_nd);
 _ode_matsol_instance1(_threadargs_);
 }}

static void 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 void nrn_init(_NrnThread* _nt, _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(double _v){double _current=0.;v=_v;{ {
   g = ( Ron + Roff ) * 1.0 ;
   i = g * ( v - Erev ) ;
   }
 _current += i;

} return _current;
}

static void nrn_cur(_NrnThread* _nt, _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);
 	{ _rhs = _nrn_current(_v);
 	}
 _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 void nrn_jacob(_NrnThread* _nt, _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 void nrn_state(_NrnThread* _nt, _Memb_list* _ml, int _type){
Node *_nd; double _v = 0.0; 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);
  }
 v=_v;
{
 { error =  release();
 if(error){fprintf(stderr,"at line 109 in file gabaa.mod:\n	SOLVE release METHOD cnexp\n"); nrn_complain(_p); abort_run(error);}
 }}}

}

static void terminal(){}

static void _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;
}

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