Rhesus Monkey Layer 3 Pyramidal Neurons: Young vs aged PFC (Coskren et al. 2015)

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Accession:168858
Layer 3 (L3) pyramidal neurons in the lateral prefrontal cortex (LPFC) of rhesus monkeys exhibit dendritic regression, spine loss and increased action potential (AP) firing rates during normal aging. The relationship between these structural and functional alterations, if any, is unknown. Computational models using the digital reconstructions with Hodgkin-Huxley and AMPA channels allowed us to assess relationships between demonstrated age-related changes and to predict physiological changes that have not yet been tested empirically. Tuning passive parameters for each model predicted significantly higher membrane resistance (Rm) in aged versus young neurons. This Rm increase alone did not account for the empirically observed fI-curves, but coupling these Rm values with subtle differences in morphology and membrane capacitance Cm did. The predicted differences in passive parameters (or other parameters with similar effects) are mathematically plausible, but must be tested empirically.
Reference:
1 . Coskren PJ, Luebke JI, Kabaso D, Wearne SL, Yadav A, Rumbell T, Hof PR, Weaver CM (2015) Functional consequences of age-related morphologic changes to pyramidal neurons of the rhesus monkey prefrontal cortex. J Comput Neurosci 38:263-83 [PubMed]
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): Neocortex V1 L2/6 pyramidal intratelencephalic GLU cell;
Channel(s): I Na,t; I A; I K; I M; I h; I K,Ca; I Calcium; I_AHP;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Influence of Dendritic Geometry; Detailed Neuronal Models; Action Potentials; Aging/Alzheimer`s;
Implementer(s): Weaver, Christina [christina.weaver at fandm.edu];
Search NeuronDB for information about:  Neocortex V1 L2/6 pyramidal intratelencephalic GLU cell; I Na,t; I A; I K; I M; I h; I K,Ca; I Calcium; I_AHP;
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CoskrenEtAl2015
HHmodel
Scripts
hoc
x86_64
.libs
kvz_nature.mod *
max.mod *
naz_nature.mod *
origlen.mod *
peak.mod *
vsource.mod *
kvz_nature.c *
kvz_nature.lo *
libnrnmech.la *
max.c *
max.lo *
mod_func.c *
mod_func.lo *
naz_nature.c *
naz_nature.lo *
origlen.c *
origlen.lo *
peak.c *
peak.lo *
special *
vsource.c *
vsource.lo *
                            
/* Created by Language version: 6.2.0 */
/* VECTORIZED */
#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 _threadargscomma_ _p, _ppvar, _thread, _nt,
#define _threadargs_ _p, _ppvar, _thread, _nt
 
#define _threadargsprotocomma_ double* _p, Datum* _ppvar, Datum* _thread, _NrnThread* _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 rs _p[0]
#define toff _p[1]
#define amp _p[2]
#define i _p[3]
#define vc _p[4]
#define on _p[5]
#define v _p[6]
#define _g _p[7]
#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;
 static Datum* _extcall_thread;
 static Prop* _extcall_prop;
 /* external NEURON variables */
 /* declaration of user functions */
 static double _hoc_icur();
 static double _hoc_vstim();
 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) {
 _extcall_prop = _prop;
 }
 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,
 "icur", _hoc_icur,
 "vstim", _hoc_vstim,
 0, 0
};
 /* declare global and static user variables */
 /* some parameters have upper and lower limits */
 static HocParmLimits _hoc_parm_limits[] = {
 "rs", 1e-09, 1e+09,
 0,0,0
};
 static HocParmUnits _hoc_parm_units[] = {
 "rs", "megohm",
 "toff", "ms",
 "amp", "mV",
 "i", "nA",
 "vc", "mV",
 0,0
};
 static double delta_t = 0.01;
 /* connect global user variables to hoc */
 static DoubScal hoc_scdoub[] = {
 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);
}
 /* connect range variables in _p that hoc is supposed to know about */
 static const char *_mechanism[] = {
 "6.2.0",
"Vsource",
 "rs",
 "toff",
 "amp",
 0,
 "i",
 "vc",
 0,
 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, 8, _prop);
 	/*initialize range parameters*/
 	rs = 1;
 	toff = 0;
 	amp = 0;
  }
 	_prop->param = _p;
 	_prop->param_size = 8;
  if (!nrn_point_prop_) {
 	_ppvar = nrn_prop_datum_alloc(_mechtype, 2, _prop);
  }
 	_prop->dparam = _ppvar;
 	/*connect ionic variables to this model*/
 
}
 static void _initlists();
 extern Symbol* hoc_lookup(const char*);
extern void _nrn_thread_reg(int, int, void(*f)(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 _vsource_reg() {
	int _vectorized = 1;
  _initlists();
 	_pointtype = point_register_mech(_mechanism,
	 nrn_alloc,nrn_cur, nrn_jacob, nrn_state, nrn_init,
	 hoc_nrnpointerindex, 1,
	 _hoc_create_pnt, _hoc_destroy_pnt, _member_func);
 _mechtype = nrn_get_mechtype(_mechanism[1]);
     _nrn_setdata_reg(_mechtype, _setdata);
  hoc_register_dparam_size(_mechtype, 2);
 	hoc_register_var(hoc_scdoub, hoc_vdoub, hoc_intfunc);
 	ivoc_help("help ?1 Vsource /Users/cweaver/research/Neuron/Coskren/MorphologyPaperTwo/Scripts/NeuronMechanisms/x86_64/vsource.mod\n");
 hoc_register_limits(_mechtype, _hoc_parm_limits);
 hoc_register_units(_mechtype, _hoc_parm_units);
 }
static int _reset;
static char *modelname = "vsource.mod";

static int error;
static int _ninits = 0;
static int _match_recurse=1;
static void _modl_cleanup(){ _match_recurse=1;}
static int icur(_threadargsproto_);
static int vstim(_threadargsproto_);
 
static int  icur ( _threadargsproto_ ) {
   if ( on ) {
     i = ( vc - v ) / rs ;
     }
   else {
     i = 0.0 ;
     }
    return 0; }
 
static double _hoc_icur(void* _vptr) {
 double _r;
   double* _p; Datum* _ppvar; Datum* _thread; _NrnThread* _nt;
   _p = ((Point_process*)_vptr)->_prop->param;
  _ppvar = ((Point_process*)_vptr)->_prop->dparam;
  _thread = _extcall_thread;
  _nt = (_NrnThread*)((Point_process*)_vptr)->_vnt;
 _r = 1.;
 icur ( _p, _ppvar, _thread, _nt );
 return(_r);
}
 
static int  vstim ( _threadargsproto_ ) {
   on = 1.0 ;
   if ( toff ) {
     at_time ( _nt, toff ) ;
     }
   if ( t < toff ) {
     vc = amp ;
     }
   else {
     vc = 0.0 ;
     on = 0.0 ;
     }
   icur ( _threadargs_ ) ;
    return 0; }
 
static double _hoc_vstim(void* _vptr) {
 double _r;
   double* _p; Datum* _ppvar; Datum* _thread; _NrnThread* _nt;
   _p = ((Point_process*)_vptr)->_prop->param;
  _ppvar = ((Point_process*)_vptr)->_prop->dparam;
  _thread = _extcall_thread;
  _nt = (_NrnThread*)((Point_process*)_vptr)->_vnt;
 _r = 1.;
 vstim ( _p, _ppvar, _thread, _nt );
 return(_r);
}

static void initmodel(double* _p, Datum* _ppvar, Datum* _thread, _NrnThread* _nt) {
  int _i; double _save;{
 {
   on = 1.0 ;
   }
 
}
}

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 EXTRACELLULAR
 _nd = _ml->_nodelist[_iml];
 if (_nd->_extnode) {
    _v = NODEV(_nd) +_nd->_extnode->_v[0];
 }else
#endif
 {
#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;{ {
   vstim ( _threadargs_ ) ;
   }
 _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 EXTRACELLULAR
 _nd = _ml->_nodelist[_iml];
 if (_nd->_extnode) {
    _v = NODEV(_nd) +_nd->_extnode->_v[0];
 }else
#endif
 {
#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;
 _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;
  }
#if EXTRACELLULAR
 if (_nd->_extnode) {
   *_nd->_extnode->_rhs[0] += _rhs;
 }
#endif
 
}}

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];
 _nd = _ml->_nodelist[_iml];
#if CACHEVEC
  if (use_cachevec) {
	VEC_D(_ni[_iml]) -= _g;
  }else
#endif
  {
	NODED(_nd) -= _g;
  }
#if EXTRACELLULAR
 if (_nd->_extnode) {
   *_nd->_extnode->_d[0] += _g;
 }
#endif
 
}}

static void nrn_state(_NrnThread* _nt, _Memb_list* _ml, int _type) {
 double _break, _save;
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];
 _nd = _ml->_nodelist[_iml];
#if EXTRACELLULAR
 _nd = _ml->_nodelist[_iml];
 if (_nd->_extnode) {
    _v = NODEV(_nd) +_nd->_extnode->_v[0];
 }else
#endif
 {
#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;
 v=_v;
{
 { {
 for (; t < _break; t += dt) {
  { icur(_p, _ppvar, _thread, _nt); }
  
}}
 t = _save;
 }}}

}

static void terminal(){}

static void _initlists(){
 double _x; double* _p = &_x;
 int _i; static int _first = 1;
  if (!_first) return;
_first = 0;
}

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

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