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 L2/3 pyramidal 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 L2/3 pyramidal 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
NeuronMechanisms
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 vhalf _p[0]
#define tpeak _p[1]
#define vpeak _p[2]
#define vpeakm _p[3]
#define dvdt2 _p[4]
#define dvdt2peak _p[5]
#define dvdtpeak _p[6]
#define onset_ref _p[7]
#define onset _p[8]
#define vonset _p[9]
#define halfwidth _p[10]
#define dvdr _p[11]
#define vrest _p[12]
#define Rmismatch _p[13]
#define Zmismatch _p[14]
#define Rback _p[15]
#define Zback _p[16]
#define Rfwd _p[17]
#define Zfwd _p[18]
#define R _p[19]
#define Z _p[20]
#define aRmismatch _p[21]
#define aZmismatch _p[22]
#define aRback _p[23]
#define aZback _p[24]
#define aRfwd _p[25]
#define aZfwd _p[26]
#define aR _p[27]
#define aZ _p[28]
#define f _p[29]
#define Xo _p[30]
#define Xlen _p[31]
#define Xsec _p[32]
#define Xfrc _p[33]
#define sign _p[34]
#define dvdt _p[35]
#define v1 _p[36]
#define v2 _p[37]
#define v3 _p[38]
#define below _p[39]
#define below_old _p[40]
#define upstroke _p[41]
#define downstroke _p[42]
#define v _p[43]
#define _g _p[44]
 
#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_check(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_pk", _hoc_setdata,
 "check_pk", _hoc_check,
 0, 0
};
 /* declare global and static user variables */
 /* some parameters have upper and lower limits */
 static HocParmLimits _hoc_parm_limits[] = {
 0,0,0
};
 static HocParmUnits _hoc_parm_units[] = {
 "vhalf_pk", "mV",
 "tpeak_pk", "ms",
 "vpeak_pk", "mV",
 "vpeakm_pk", "mV",
 "dvdt2_pk", "mV/ms*ms",
 "dvdt2peak_pk", "mV/ms*ms",
 "dvdtpeak_pk", "mV/ms",
 "onset_ref_pk", "mV/ms",
 "onset_pk", "ms",
 "vonset_pk", "mV",
 "halfwidth_pk", "ms",
 "dvdr_pk", "mv/micron",
 "vrest_pk", "mV",
 "Rmismatch_pk", "1",
 "Zmismatch_pk", "1",
 "Rback_pk", "Mohm",
 "Zback_pk", "Mohm",
 "Rfwd_pk", "Mohm",
 "Zfwd_pk", "Mohm",
 "R_pk", "Mohm",
 "Z_pk", "Mohm",
 "aRmismatch_pk", "1",
 "aZmismatch_pk", "1",
 "aRback_pk", "Mohm",
 "aZback_pk", "Mohm",
 "aRfwd_pk", "Mohm",
 "aZfwd_pk", "Mohm",
 "aR_pk", "Mohm",
 "aZ_pk", "Mohm",
 "Xo_pk", "1",
 "Xlen_pk", "1",
 "Xsec_pk", "1",
 "Xfrc_pk", "1",
 "sign_pk", "1",
 0,0
};
 static double delta_t = 1;
 /* 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 int _ode_count(int);
 /* connect range variables in _p that hoc is supposed to know about */
 static const char *_mechanism[] = {
 "6.2.0",
"pk",
 "vhalf_pk",
 0,
 "tpeak_pk",
 "vpeak_pk",
 "vpeakm_pk",
 "dvdt2_pk",
 "dvdt2peak_pk",
 "dvdtpeak_pk",
 "onset_ref_pk",
 "onset_pk",
 "vonset_pk",
 "halfwidth_pk",
 "dvdr_pk",
 "vrest_pk",
 "Rmismatch_pk",
 "Zmismatch_pk",
 "Rback_pk",
 "Zback_pk",
 "Rfwd_pk",
 "Zfwd_pk",
 "R_pk",
 "Z_pk",
 "aRmismatch_pk",
 "aZmismatch_pk",
 "aRback_pk",
 "aZback_pk",
 "aRfwd_pk",
 "aZfwd_pk",
 "aR_pk",
 "aZ_pk",
 "f_pk",
 "Xo_pk",
 "Xlen_pk",
 "Xsec_pk",
 "Xfrc_pk",
 "sign_pk",
 0,
 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, 45, _prop);
 	/*initialize range parameters*/
 	vhalf = 0;
 	_prop->param = _p;
 	_prop->param_size = 45;
 
}
 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 _peak_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_dparam_size(_mechtype, 0);
 	hoc_register_cvode(_mechtype, _ode_count, 0, 0, 0);
 	hoc_register_var(hoc_scdoub, hoc_vdoub, hoc_intfunc);
 	ivoc_help("help ?1 pk /Users/cweaver/research/Neuron/Coskren/MorphologyPaperTwo/Scripts/NeuronMechanisms/x86_64/peak.mod\n");
 hoc_register_limits(_mechtype, _hoc_parm_limits);
 hoc_register_units(_mechtype, _hoc_parm_units);
 }
static int _reset;
static char *modelname = "peak.mod";

static int error;
static int _ninits = 0;
static int _match_recurse=1;
static void _modl_cleanup(){ _match_recurse=1;}
static int check(_threadargsproto_);
 
static int  check ( _threadargsproto_ ) {
   if ( v > vpeak  && vpeakm  == - 100.0 ) {
     tpeak = t ;
     vpeak = v ;
     }
   if ( v + 4.0 < vpeak ) {
     vpeakm = 1.0 ;
     }
   v1 = v2 ;
   v2 = v3 ;
   v3 = v ;
   dvdt = ( v3 - v2 ) / ( dt ) ;
   dvdt2 = ( v3 - 2.0 * v2 + v1 ) / ( dt * dt ) ;
   if ( dvdt > dvdtpeak ) {
     dvdtpeak = dvdt ;
     }
   if ( dvdt2 > dvdt2peak ) {
     dvdt2peak = dvdt2 ;
     }
   if ( dvdt > onset_ref  && onset  == 0.0  && t > 1.0 ) {
     onset = t - dt ;
     vonset = v2 ;
     }
   below = 0.0 ;
   if ( vhalf > v ) {
     below = 1.0 ;
     }
   if ( below  == 0.0  && below_old  == 1.0  && upstroke  == 0.0 ) {
     upstroke = t ;
     }
   if ( below  == 1.0  && below_old  == 0.0  && downstroke  == 0.0 ) {
     downstroke = t ;
     }
   halfwidth = downstroke - upstroke ;
   below_old = below ;
    return 0; }
 
static void _hoc_check(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 = 1.;
 check ( _p, _ppvar, _thread, _nt );
 hoc_retpushx(_r);
}
 
static int _ode_count(int _type){ hoc_execerror("pk", "cannot be used with CVODE"); return 0;}

static void initmodel(double* _p, Datum* _ppvar, Datum* _thread, _NrnThread* _nt) {
  int _i; double _save;{
 {
   tpeak = 0.0 ;
   vpeak = - 100.0 ;
   vpeakm = - 100.0 ;
   onset = 0.0 ;
   dvdtpeak = 0.0 ;
   dvdt2peak = 0.0 ;
   downstroke = 0.0 ;
   upstroke = 0.0 ;
   vrest = v ;
   check ( _threadargs_ ) ;
   }
 
}
}

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;{
} 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);
  }
 
}}

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 _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 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) {
  { check(_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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