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 */
/* VECTORIZED */
#define NRN_VECTORIZED 1
#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__ih
#define _nrn_initial _nrn_initial__ih
#define nrn_cur _nrn_cur__ih
#define _nrn_current _nrn_current__ih
#define nrn_jacob _nrn_jacob__ih
#define nrn_state _nrn_state__ih
#define _net_receive _net_receive__ih 
#define state state__ih 
 
#define _threadargscomma_ _p, _ppvar, _thread, _nt,
#define _threadargsprotocomma_ double* _p, Datum* _ppvar, Datum* _thread, _NrnThread* _nt,
#define _threadargs_ _p, _ppvar, _thread, _nt
#define _threadargsproto_ double* _p, Datum* _ppvar, Datum* _thread, _NrnThread* _nt
 	/*SUPPRESS 761*/
	/*SUPPRESS 762*/
	/*SUPPRESS 763*/
	/*SUPPRESS 765*/
	 extern double *getarg();
 /* Thread safe. No static _p or _ppvar. */
 
#define t _nt->_t
#define dt _nt->_dt
#define gbar _p[0]
#define ascale _p[1]
#define bscale _p[2]
#define ashift _p[3]
#define aslope _p[4]
#define bslope _p[5]
#define i _p[6]
#define m _p[7]
#define Dm _p[8]
#define v _p[9]
#define _g _p[10]
 
#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;
 static Datum* _extcall_thread;
 static Prop* _extcall_prop;
 /* external NEURON variables */
 /* declaration of user functions */
 static void _hoc_alpha(void);
 static void _hoc_beta(void);
 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 void _nrn_setdata_reg(int, void(*)(Prop*));
 static void _setdata(Prop* _prop) {
 _extcall_prop = _prop;
 }
 static void _hoc_setdata() {
 Prop *_prop, *hoc_getdata_range(int);
 _prop = hoc_getdata_range(_mechtype);
   _setdata(_prop);
 hoc_retpushx(1.);
}
 /* connect user functions to hoc names */
 static VoidFunc hoc_intfunc[] = {
 "setdata_ih", _hoc_setdata,
 "alpha_ih", _hoc_alpha,
 "beta_ih", _hoc_beta,
 0, 0
};
#define alpha alpha_ih
#define beta beta_ih
 extern double alpha( _threadargsprotocomma_ double );
 extern double beta( _threadargsprotocomma_ double );
 /* declare global and static user variables */
#define erev erev_ih
 double erev = -45;
#define q10 q10_ih
 double q10 = 2.2;
 /* some parameters have upper and lower limits */
 static HocParmLimits _hoc_parm_limits[] = {
 0,0,0
};
 static HocParmUnits _hoc_parm_units[] = {
 "erev_ih", "mV",
 "gbar_ih", "S/cm2",
 "i_ih", "mA/cm2",
 0,0
};
 static double delta_t = 0.01;
 static double m0 = 0;
 /* connect global user variables to hoc */
 static DoubScal hoc_scdoub[] = {
 "erev_ih", &erev_ih,
 "q10_ih", &q10_ih,
 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 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[0]._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",
"ih",
 "gbar_ih",
 "ascale_ih",
 "bscale_ih",
 "ashift_ih",
 "aslope_ih",
 "bslope_ih",
 0,
 "i_ih",
 0,
 "m_ih",
 0,
 0};
 
extern Prop* need_memb(Symbol*);

static void nrn_alloc(Prop* _prop) {
	Prop *prop_ion;
	double *_p; Datum *_ppvar;
 	_p = nrn_prop_data_alloc(_mechtype, 11, _prop);
 	/*initialize range parameters*/
 	gbar = 0.00015;
 	ascale = 0.00643;
 	bscale = 0.193;
 	ashift = 154.9;
 	aslope = 11.9;
 	bslope = 33.1;
 	_prop->param = _p;
 	_prop->param_size = 11;
 	_ppvar = nrn_prop_datum_alloc(_mechtype, 1, _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
};
 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 _h_kole_reg() {
	int _vectorized = 1;
  _initlists();
 	register_mech(_mechanism, nrn_alloc,nrn_cur, nrn_jacob, nrn_state, nrn_init, hoc_nrnpointerindex, 1);
 _mechtype = nrn_get_mechtype(_mechanism[1]);
     _nrn_setdata_reg(_mechtype, _setdata);
  hoc_register_prop_size(_mechtype, 11, 1);
  hoc_register_dparam_semantics(_mechtype, 0, "cvodeieq");
 	hoc_register_cvode(_mechtype, _ode_count, _ode_map, _ode_spec, _ode_matsol);
 	hoc_register_tolerance(_mechtype, _hoc_state_tol, &_atollist);
 	hoc_register_var(hoc_scdoub, hoc_vdoub, hoc_intfunc);
 	ivoc_help("help ?1 ih /Users/Penny/Dropbox/ModelDB/mod/x86_64/h_kole.mod\n");
 hoc_register_limits(_mechtype, _hoc_parm_limits);
 hoc_register_units(_mechtype, _hoc_parm_units);
 }
static int _reset;
static char *modelname = "Ih-current";

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[1], _dlist1[1];
 static int state(_threadargsproto_);
 
double alpha ( _threadargsprotocomma_ double _lv ) {
   double _lalpha;
 _lalpha = ascale * ( _lv + ashift ) / ( exp ( ( _lv + ashift ) / aslope ) - 1.0 ) ;
   
return _lalpha;
 }
 
static void _hoc_alpha(void) {
  double _r;
   double* _p; Datum* _ppvar; Datum* _thread; _NrnThread* _nt;
   if (_extcall_prop) {_p = _extcall_prop->param; _ppvar = _extcall_prop->dparam;}else{ _p = (double*)0; _ppvar = (Datum*)0; }
  _thread = _extcall_thread;
  _nt = nrn_threads;
 _r =  alpha ( _p, _ppvar, _thread, _nt, *getarg(1) );
 hoc_retpushx(_r);
}
 
double beta ( _threadargsprotocomma_ double _lv ) {
   double _lbeta;
 _lbeta = bscale * exp ( _lv / bslope ) ;
   
return _lbeta;
 }
 
static void _hoc_beta(void) {
  double _r;
   double* _p; Datum* _ppvar; Datum* _thread; _NrnThread* _nt;
   if (_extcall_prop) {_p = _extcall_prop->param; _ppvar = _extcall_prop->dparam;}else{ _p = (double*)0; _ppvar = (Datum*)0; }
  _thread = _extcall_thread;
  _nt = nrn_threads;
 _r =  beta ( _p, _ppvar, _thread, _nt, *getarg(1) );
 hoc_retpushx(_r);
}
 
/*CVODE*/
 static int _ode_spec1 (double* _p, Datum* _ppvar, Datum* _thread, _NrnThread* _nt) {int _reset = 0; {
   Dm = ( 1.0 - m ) * alpha ( _threadargscomma_ v ) - m * beta ( _threadargscomma_ v ) ;
   }
 return _reset;
}
 static int _ode_matsol1 (double* _p, Datum* _ppvar, Datum* _thread, _NrnThread* _nt) {
 Dm = Dm  / (1. - dt*( ( ( ( - 1.0 ) ) )*( alpha ( _threadargscomma_ v ) ) - ( 1.0 )*( beta ( _threadargscomma_ v ) ) )) ;
  return 0;
}
 /*END CVODE*/
 static int state (double* _p, Datum* _ppvar, Datum* _thread, _NrnThread* _nt) { {
    m = m + (1. - exp(dt*(( ( ( - 1.0 ) ) )*( alpha ( _threadargscomma_ v ) ) - ( 1.0 )*( beta ( _threadargscomma_ v ) ))))*(- ( ( ( 1.0 ) )*( alpha ( _threadargscomma_ v ) ) ) / ( ( ( ( - 1.0 ) ) )*( alpha ( _threadargscomma_ v ) ) - ( 1.0 )*( beta ( _threadargscomma_ v ) ) ) - m) ;
   }
  return 0;
}
 
static int _ode_count(int _type){ return 1;}
 
static void _ode_spec(_NrnThread* _nt, _Memb_list* _ml, int _type) {
   double* _p; Datum* _ppvar; 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 (_p, _ppvar, _thread, _nt);
 }}
 
static void _ode_map(int _ieq, double** _pv, double** _pvdot, double* _pp, Datum* _ppd, double* _atol, int _type) { 
	double* _p; Datum* _ppvar;
 	int _i; _p = _pp; _ppvar = _ppd;
	_cvode_ieq = _ieq;
	for (_i=0; _i < 1; ++_i) {
		_pv[_i] = _pp + _slist1[_i];  _pvdot[_i] = _pp + _dlist1[_i];
		_cvode_abstol(_atollist, _atol, _i);
	}
 }
 
static void _ode_matsol_instance1(_threadargsproto_) {
 _ode_matsol1 (_p, _ppvar, _thread, _nt);
 }
 
static void _ode_matsol(_NrnThread* _nt, _Memb_list* _ml, int _type) {
   double* _p; Datum* _ppvar; 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(double* _p, Datum* _ppvar, Datum* _thread, _NrnThread* _nt) {
  int _i; double _save;{
  m = m0;
 {
   double _la , _lb ;
 _la = alpha ( _threadargscomma_ v ) ;
   _lb = beta ( _threadargscomma_ v ) ;
   m = _la / ( _la + _lb ) ;
   }
 
}
}

static void nrn_init(_NrnThread* _nt, _Memb_list* _ml, int _type){
double* _p; Datum* _ppvar; Datum* _thread;
Node *_nd; double _v; int* _ni; int _iml, _cntml;
#if CACHEVEC
    _ni = _ml->_nodeindices;
#endif
_cntml = _ml->_nodecount;
_thread = _ml->_thread;
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);
  }
 v = _v;
 initmodel(_p, _ppvar, _thread, _nt);
}
}

static double _nrn_current(double* _p, Datum* _ppvar, Datum* _thread, _NrnThread* _nt, double _v){double _current=0.;v=_v;{ {
   i = gbar * m * ( v - erev ) ;
   }
 _current += i;

} return _current;
}

static void nrn_cur(_NrnThread* _nt, _Memb_list* _ml, int _type) {
double* _p; Datum* _ppvar; Datum* _thread;
Node *_nd; int* _ni; double _rhs, _v; int _iml, _cntml;
#if CACHEVEC
    _ni = _ml->_nodeindices;
#endif
_cntml = _ml->_nodecount;
_thread = _ml->_thread;
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(_p, _ppvar, _thread, _nt, _v + .001);
 	{ _rhs = _nrn_current(_p, _ppvar, _thread, _nt, _v);
 	}
 _g = (_g - _rhs)/.001;
#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) {
double* _p; Datum* _ppvar; Datum* _thread;
Node *_nd; int* _ni; int _iml, _cntml;
#if CACHEVEC
    _ni = _ml->_nodeindices;
#endif
_cntml = _ml->_nodecount;
_thread = _ml->_thread;
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) {
double* _p; Datum* _ppvar; Datum* _thread;
Node *_nd; double _v = 0.0; int* _ni; int _iml, _cntml;
#if CACHEVEC
    _ni = _ml->_nodeindices;
#endif
_cntml = _ml->_nodecount;
_thread = _ml->_thread;
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;
{
 {   state(_p, _ppvar, _thread, _nt);
  }}}

}

static void terminal(){}

static void _initlists(){
 double _x; double* _p = &_x;
 int _i; static int _first = 1;
  if (!_first) return;
 _slist1[0] = &(m) - _p;  _dlist1[0] = &(Dm) - _p;
_first = 0;
}

#if defined(__cplusplus)
} /* extern "C" */
#endif

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