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__kl
#define _nrn_initial _nrn_initial__kl
#define nrn_cur _nrn_cur__kl
#define _nrn_current _nrn_current__kl
#define nrn_jacob _nrn_jacob__kl
#define nrn_state _nrn_state__kl
#define _net_receive _net_receive__kl 
#define rates rates__kl 
#define states states__kl 
 
#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 gbar _p[0]
#define gka _p[1]
#define n _p[2]
#define l _p[3]
#define ek _p[4]
#define Dn _p[5]
#define Dl _p[6]
#define ik _p[7]
#define _g _p[8]
#define _ion_ek	*_ppvar[0]._pval
#define _ion_ik	*_ppvar[1]._pval
#define _ion_dikdv	*_ppvar[2]._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 */
 extern double celsius;
 /* declaration of user functions */
 static void _hoc_alpl(void);
 static void _hoc_alpn(void);
 static void _hoc_betl(void);
 static void _hoc_betn(void);
 static void _hoc_rates(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) {
 _p = _prop->param; _ppvar = _prop->dparam;
 }
 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_kl", _hoc_setdata,
 "alpl_kl", _hoc_alpl,
 "alpn_kl", _hoc_alpn,
 "betl_kl", _hoc_betl,
 "betn_kl", _hoc_betn,
 "rates_kl", _hoc_rates,
 0, 0
};
#define alpl alpl_kl
#define alpn alpn_kl
#define betl betl_kl
#define betn betn_kl
 extern double alpl( double );
 extern double alpn( double );
 extern double betl( double );
 extern double betn( double );
 /* declare global and static user variables */
#define a0n a0n_kl
 double a0n = 0.05;
#define a0l a0l_kl
 double a0l = 0.05;
#define gml gml_kl
 double gml = 1;
#define gmn gmn_kl
 double gmn = 0.55;
#define linf linf_kl
 double linf = 0;
#define lmin lmin_kl
 double lmin = 2;
#define ninf ninf_kl
 double ninf = 0;
#define nmin nmin_kl
 double nmin = 0.1;
#define pw pw_kl
 double pw = -1;
#define qtl qtl_kl
 double qtl = 1;
#define q10 q10_kl
 double q10 = 5;
#define qq qq_kl
 double qq = 5;
#define taun taun_kl
 double taun = 0;
#define taul taul_kl
 double taul = 0;
#define tq tq_kl
 double tq = -40;
#define vhalfl vhalfl_kl
 double vhalfl = -56;
#define vhalfn vhalfn_kl
 double vhalfn = 11;
#define zetal zetal_kl
 double zetal = 3;
#define zetan zetan_kl
 double zetan = -1.5;
 /* some parameters have upper and lower limits */
 static HocParmLimits _hoc_parm_limits[] = {
 0,0,0
};
 static HocParmUnits _hoc_parm_units[] = {
 "vhalfn_kl", "mV",
 "vhalfl_kl", "mV",
 "a0l_kl", "/ms",
 "a0n_kl", "/ms",
 "zetan_kl", "1",
 "zetal_kl", "1",
 "gmn_kl", "1",
 "gml_kl", "1",
 "lmin_kl", "mS",
 "nmin_kl", "mS",
 "pw_kl", "1",
 0,0
};
 static double delta_t = 0.01;
 static double l0 = 0;
 static double n0 = 0;
 static double v = 0;
 /* connect global user variables to hoc */
 static DoubScal hoc_scdoub[] = {
 "vhalfn_kl", &vhalfn_kl,
 "vhalfl_kl", &vhalfl_kl,
 "a0l_kl", &a0l_kl,
 "a0n_kl", &a0n_kl,
 "zetan_kl", &zetan_kl,
 "zetal_kl", &zetal_kl,
 "gmn_kl", &gmn_kl,
 "gml_kl", &gml_kl,
 "lmin_kl", &lmin_kl,
 "nmin_kl", &nmin_kl,
 "pw_kl", &pw_kl,
 "tq_kl", &tq_kl,
 "qq_kl", &qq_kl,
 "q10_kl", &q10_kl,
 "qtl_kl", &qtl_kl,
 "ninf_kl", &ninf_kl,
 "linf_kl", &linf_kl,
 "taul_kl", &taul_kl,
 "taun_kl", &taun_kl,
 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[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",
"kl",
 "gbar_kl",
 0,
 "gka_kl",
 0,
 "n_kl",
 "l_kl",
 0,
 0};
 static Symbol* _k_sym;
 
extern Prop* need_memb(Symbol*);

static void nrn_alloc(Prop* _prop) {
	Prop *prop_ion;
	double *_p; Datum *_ppvar;
 	_p = nrn_prop_data_alloc(_mechtype, 9, _prop);
 	/*initialize range parameters*/
 	gbar = 0.01;
 	_prop->param = _p;
 	_prop->param_size = 9;
 	_ppvar = nrn_prop_datum_alloc(_mechtype, 4, _prop);
 	_prop->dparam = _ppvar;
 	/*connect ionic variables to this model*/
 prop_ion = need_memb(_k_sym);
 nrn_promote(prop_ion, 0, 1);
 	_ppvar[0]._pval = &prop_ion->param[0]; /* ek */
 	_ppvar[1]._pval = &prop_ion->param[3]; /* ik */
 	_ppvar[2]._pval = &prop_ion->param[4]; /* _ion_dikdv */
 
}
 static void _initlists();
  /* some states have an absolute tolerance */
 static Symbol** _atollist;
 static HocStateTolerance _hoc_state_tol[] = {
 0,0
};
 static void _update_ion_pointer(Datum*);
 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 _IL_reg() {
	int _vectorized = 0;
  _initlists();
 	ion_reg("k", -10000.);
 	_k_sym = hoc_lookup("k_ion");
 	register_mech(_mechanism, nrn_alloc,nrn_cur, nrn_jacob, nrn_state, nrn_init, hoc_nrnpointerindex, 0);
 _mechtype = nrn_get_mechtype(_mechanism[1]);
     _nrn_setdata_reg(_mechtype, _setdata);
     _nrn_thread_reg(_mechtype, 2, _update_ion_pointer);
  hoc_register_prop_size(_mechtype, 9, 4);
  hoc_register_dparam_semantics(_mechtype, 0, "k_ion");
  hoc_register_dparam_semantics(_mechtype, 1, "k_ion");
  hoc_register_dparam_semantics(_mechtype, 2, "k_ion");
  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);
 	hoc_register_var(hoc_scdoub, hoc_vdoub, hoc_intfunc);
 	ivoc_help("help ?1 kl /Users/Penny/Dropbox/ModelDB/mod/x86_64/IL.mod\n");
 hoc_register_limits(_mechtype, _hoc_parm_limits);
 hoc_register_units(_mechtype, _hoc_parm_units);
 }
static int _reset;
static char *modelname = "K-A channel from Klee Ficker and Heinemann";

static int error;
static int _ninits = 0;
static int _match_recurse=1;
static void _modl_cleanup(){ _match_recurse=1;}
static int rates(double);
 
static int _ode_spec1(_threadargsproto_);
/*static int _ode_matsol1(_threadargsproto_);*/
 static int _slist1[2], _dlist1[2];
 static int states(_threadargsproto_);
 
double alpn (  double _lv ) {
   double _lalpn;
 double _lzeta ;
 _lzeta = zetan + pw / ( 1.0 + exp ( ( _lv - tq ) / qq ) ) ;
   _lalpn = exp ( 1.e-3 * _lzeta * ( _lv - vhalfn ) * 9.648e4 / ( 8.315 * ( 273.16 + celsius ) ) ) ;
   
return _lalpn;
 }
 
static void _hoc_alpn(void) {
  double _r;
   _r =  alpn (  *getarg(1) );
 hoc_retpushx(_r);
}
 
double betn (  double _lv ) {
   double _lbetn;
 double _lzeta ;
 _lzeta = zetan + pw / ( 1.0 + exp ( ( _lv - tq ) / qq ) ) ;
   _lbetn = exp ( 1.e-3 * _lzeta * gmn * ( _lv - vhalfn ) * 9.648e4 / ( 8.315 * ( 273.16 + celsius ) ) ) ;
   
return _lbetn;
 }
 
static void _hoc_betn(void) {
  double _r;
   _r =  betn (  *getarg(1) );
 hoc_retpushx(_r);
}
 
double alpl (  double _lv ) {
   double _lalpl;
 _lalpl = exp ( 1.e-3 * zetal * ( _lv - vhalfl ) * 9.648e4 / ( 8.315 * ( 273.16 + celsius ) ) ) ;
   
return _lalpl;
 }
 
static void _hoc_alpl(void) {
  double _r;
   _r =  alpl (  *getarg(1) );
 hoc_retpushx(_r);
}
 
double betl (  double _lv ) {
   double _lbetl;
 _lbetl = exp ( 1.e-3 * zetal * gml * ( _lv - vhalfl ) * 9.648e4 / ( 8.315 * ( 273.16 + celsius ) ) ) ;
   
return _lbetl;
 }
 
static void _hoc_betl(void) {
  double _r;
   _r =  betl (  *getarg(1) );
 hoc_retpushx(_r);
}
 
/*CVODE*/
 static int _ode_spec1 () {_reset=0;
 {
   rates ( _threadargscomma_ v ) ;
   Dn = ( ninf - n ) / taun ;
   Dl = ( linf - l ) / taul ;
   }
 return _reset;
}
 static int _ode_matsol1 () {
 rates ( _threadargscomma_ v ) ;
 Dn = Dn  / (1. - dt*( ( ( ( - 1.0 ) ) ) / taun )) ;
 Dl = Dl  / (1. - dt*( ( ( ( - 1.0 ) ) ) / taul )) ;
  return 0;
}
 /*END CVODE*/
 static int states () {_reset=0;
 {
   rates ( _threadargscomma_ v ) ;
    n = n + (1. - exp(dt*(( ( ( - 1.0 ) ) ) / taun)))*(- ( ( ( ninf ) ) / taun ) / ( ( ( ( - 1.0 ) ) ) / taun ) - n) ;
    l = l + (1. - exp(dt*(( ( ( - 1.0 ) ) ) / taul)))*(- ( ( ( linf ) ) / taul ) / ( ( ( ( - 1.0 ) ) ) / taul ) - l) ;
   }
  return 0;
}
 
static int  rates (  double _lv ) {
   double _la , _lqt ;
 _lqt = pow( q10 , ( ( celsius - 24.0 ) / 10.0 ) ) ;
   _la = alpn ( _threadargscomma_ _lv ) ;
   taun = betn ( _threadargscomma_ _lv ) / ( _lqt * a0n * ( 1.0 + _la ) ) ;
   if ( taun < nmin ) {
     taun = nmin ;
     }
   ninf = 1.0 / ( 1.0 + exp ( - ( _lv + 60.0 ) / 20.0 ) ) ;
   taul = 0.26 * ( _lv + 50.0 ) / qtl * 20.0 ;
   if ( taul < lmin / qtl ) {
     taul = lmin / qtl ;
     }
   linf = 1.0 / ( 1.0 + exp ( ( _lv + 30.0 ) / 20.0 ) ) ;
    return 0; }
 
static void _hoc_rates(void) {
  double _r;
   _r = 1.;
 rates (  *getarg(1) );
 hoc_retpushx(_r);
}
 
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);
  ek = _ion_ek;
     _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);
  ek = _ion_ek;
 _ode_matsol_instance1(_threadargs_);
 }}
 extern void nrn_update_ion_pointer(Symbol*, Datum*, int, int);
 static void _update_ion_pointer(Datum* _ppvar) {
   nrn_update_ion_pointer(_k_sym, _ppvar, 0, 0);
   nrn_update_ion_pointer(_k_sym, _ppvar, 1, 3);
   nrn_update_ion_pointer(_k_sym, _ppvar, 2, 4);
 }

static void initmodel() {
  int _i; double _save;_ninits++;
 _save = t;
 t = 0.0;
{
  l = l0;
  n = n0;
 {
   rates ( _threadargscomma_ v ) ;
   n = ninf ;
   l = linf ;
   }
  _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];
#if CACHEVEC
  if (use_cachevec) {
    _v = VEC_V(_ni[_iml]);
  }else
#endif
  {
    _nd = _ml->_nodelist[_iml];
    _v = NODEV(_nd);
  }
 v = _v;
  ek = _ion_ek;
 initmodel();
 }}

static double _nrn_current(double _v){double _current=0.;v=_v;{ {
   gka = gbar * n * l ;
   ik = gka * ( v - ek ) ;
   }
 _current += ik;

} 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);
  }
  ek = _ion_ek;
 _g = _nrn_current(_v + .001);
 	{ double _dik;
  _dik = ik;
 _rhs = _nrn_current(_v);
  _ion_dikdv += (_dik - ik)/.001 ;
 	}
 _g = (_g - _rhs)/.001;
  _ion_ik += ik ;
#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;
{
  ek = _ion_ek;
 { error =  states();
 if(error){fprintf(stderr,"at line 72 in file IL.mod:\n	SOLVE states 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] = &(n) - _p;  _dlist1[0] = &(Dn) - _p;
 _slist1[1] = &(l) - _p;  _dlist1[1] = &(Dl) - _p;
_first = 0;
}

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