Fast Spiking Basket cells (Tzilivaki et al 2019)

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Accession:237595
"Interneurons are critical for the proper functioning of neural circuits. While often morphologically complex, dendritic integration and its role in neuronal output have been ignored for decades, treating interneurons as linear point neurons. Exciting new findings suggest that interneuron dendrites support complex, nonlinear computations: sublinear integration of EPSPs in the cerebellum, coupled to supralinear calcium accumulations and supralinear voltage integration in the hippocampus. These findings challenge the point neuron dogma and call for a new theory of interneuron arithmetic. Using detailed, biophysically constrained models, we predict that dendrites of FS basket cells in both hippocampus and mPFC come in two flavors: supralinear, supporting local sodium spikes within large-volume branches and sublinear, in small-volume branches. Synaptic activation of varying sets of these dendrites leads to somatic firing variability that cannot be explained by the point neuron reduction. Instead, a 2-stage Artificial Neural Network (ANN), with both sub- and supralinear hidden nodes, captures most of the variance. We propose that FS basket cells have substantially expanded computational capabilities sub-served by their non-linear dendrites and act as a 2-layer ANN."
Reference:
1 . Tzilivaki A, Kastellakis G, Poirazi P (2019) Challenging the point neuron dogma: FS basket cells as 2-stage nonlinear integrators Nature Communications 10(1):3664 [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: Hippocampus; Prefrontal cortex (PFC);
Cell Type(s): Hippocampus CA3 interneuron basket GABA cell; Neocortex layer 5 interneuron;
Channel(s):
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON; MATLAB; Python;
Model Concept(s): Active Dendrites; Detailed Neuronal Models;
Implementer(s): Tzilivaki, Alexandra [alexandra.tzilivaki at charite.de]; Kastellakis, George [gkastel at gmail.com];
Search NeuronDB for information about:  Hippocampus CA3 interneuron basket GABA cell;
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TzilivakiEtal_FSBCs_model
Multicompartmental_Biophysical_models
mechanism
x86_64
.libs
ampa.mod *
ampain.mod *
cadyn.mod *
cadynin.mod *
cal.mod *
calc.mod *
calcb.mod *
can.mod *
cancr.mod *
canin.mod *
car.mod *
cat.mod *
catcb.mod *
cpampain.mod *
gabaa.mod *
gabaain.mod *
gabab.mod *
h.mod *
hcb.mod *
hin.mod *
ican.mod *
iccb.mod *
iccr.mod *
icin.mod *
iks.mod *
ikscb.mod *
ikscr.mod *
iksin.mod *
kadist.mod *
kadistcr.mod *
kadistin.mod *
kaprox.mod *
kaproxcb.mod *
kaproxin.mod *
kca.mod *
kcain.mod *
kct.mod *
kctin.mod *
kdr.mod *
kdrcb.mod *
kdrcr.mod *
kdrin.mod *
naf.mod *
nafcb.mod *
nafcr.mod *
nafin.mod *
nafx.mod *
nap.mod *
netstim.mod *
NMDA.mod *
NMDAIN.mod *
sinclamp.mod *
vecstim.mod *
ampa.c
ampa.lo
ampain.c
ampain.lo
cadyn.c
cadyn.lo
cadynin.c
cadynin.lo
cal.c
cal.lo
calc.c
calc.lo
calcb.c
calcb.lo
can.c
can.lo
cancr.c
cancr.lo
canin.c
canin.lo
car.c
car.lo
cat.c
cat.lo
catcb.c
catcb.lo
cpampain.c
cpampain.lo
gabaa.c
gabaa.lo
gabaain.c
gabaain.lo
gabab.c
gabab.lo
h.c
h.lo
hcb.c
hcb.lo
hin.c
hin.lo
ican.c
ican.lo
iccb.c
iccb.lo
iccr.c
iccr.lo
icin.c
icin.lo
iks.c
iks.lo
ikscb.c
ikscb.lo
ikscr.c
ikscr.lo
iksin.c
iksin.lo
kadist.c
kadist.lo
kadistcr.c
kadistcr.lo
kadistin.c
kadistin.lo
kaprox.c
kaprox.lo
kaproxcb.c
kaproxcb.lo
kaproxin.c
kaproxin.lo
kca.c
kca.lo
kcain.c
kcain.lo
kct.c
kct.lo
kctin.c
kctin.lo
kdr.c
kdr.lo
kdrcb.c
kdrcb.lo
kdrcr.c
kdrcr.lo
kdrin.c
kdrin.lo
libnrnmech.la *
mod_func.c
mod_func.lo
naf.c
naf.lo
nafcb.c
nafcb.lo
nafcr.c
nafcr.lo
nafin.c
nafin.lo
nafx.c
nafx.lo
nap.c
nap.lo
netstim.c
netstim.lo
NMDA.c
NMDA.lo
NMDAIN.c
NMDAIN.lo
sinclamp.c
sinclamp.lo
special
vecstim.c
vecstim.lo
                            
/* Created by Language version: 6.2.0 */
/* 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__calc
#define _nrn_initial _nrn_initial__calc
#define nrn_cur _nrn_cur__calc
#define _nrn_current _nrn_current__calc
#define nrn_jacob _nrn_jacob__calc
#define nrn_state _nrn_state__calc
#define _net_receive _net_receive__calc 
#define rates rates__calc 
#define states states__calc 
 
#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 gcabar _p[0]
#define ica _p[1]
#define tau_m _p[2]
#define m_inf _p[3]
#define m _p[4]
#define cai _p[5]
#define cao _p[6]
#define Dm _p[7]
#define tadj _p[8]
#define v _p[9]
#define _g _p[10]
#define _ion_cai	*_ppvar[0]._pval
#define _ion_cao	*_ppvar[1]._pval
#define _ion_ica	*_ppvar[2]._pval
#define _ion_dicadv	*_ppvar[3]._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 */
 extern double celsius;
 /* declaration of user functions */
 static void _hoc_ghk(void);
 static void _hoc_rates(void);
 static void _hoc_states(void);
 static void _hoc_vtrap(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_calc", _hoc_setdata,
 "ghk_calc", _hoc_ghk,
 "rates_calc", _hoc_rates,
 "states_calc", _hoc_states,
 "vtrap_calc", _hoc_vtrap,
 0, 0
};
#define ghk ghk_calc
#define vtrap vtrap_calc
 extern double ghk( _threadargsprotocomma_ double , double , double , double );
 extern double vtrap( _threadargsprotocomma_ double , double );
 /* 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[] = {
 "gcabar_calc", "cm/s",
 "ica_calc", "mA/cm2",
 "tau_m_calc", "ms",
 0,0
};
 static double delta_t = 1;
 static double m0 = 0;
 /* 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",
"calc",
 "gcabar_calc",
 0,
 "ica_calc",
 "tau_m_calc",
 "m_inf_calc",
 0,
 "m_calc",
 0,
 0};
 static Symbol* _ca_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, 11, _prop);
 	/*initialize range parameters*/
 	gcabar = 0.000276;
 	_prop->param = _p;
 	_prop->param_size = 11;
 	_ppvar = nrn_prop_datum_alloc(_mechtype, 4, _prop);
 	_prop->dparam = _ppvar;
 	/*connect ionic variables to this model*/
 prop_ion = need_memb(_ca_sym);
 nrn_promote(prop_ion, 1, 0);
 	_ppvar[0]._pval = &prop_ion->param[1]; /* cai */
 	_ppvar[1]._pval = &prop_ion->param[2]; /* cao */
 	_ppvar[2]._pval = &prop_ion->param[3]; /* ica */
 	_ppvar[3]._pval = &prop_ion->param[4]; /* _ion_dicadv */
 
}
 static void _initlists();
 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 _calc_reg() {
	int _vectorized = 1;
  _initlists();
 	ion_reg("ca", -10000.);
 	_ca_sym = hoc_lookup("ca_ion");
 	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);
     _nrn_thread_reg(_mechtype, 2, _update_ion_pointer);
  hoc_register_prop_size(_mechtype, 11, 4);
  hoc_register_dparam_semantics(_mechtype, 0, "ca_ion");
  hoc_register_dparam_semantics(_mechtype, 1, "ca_ion");
  hoc_register_dparam_semantics(_mechtype, 2, "ca_ion");
  hoc_register_dparam_semantics(_mechtype, 3, "ca_ion");
 	hoc_register_cvode(_mechtype, _ode_count, 0, 0, 0);
 	hoc_register_var(hoc_scdoub, hoc_vdoub, hoc_intfunc);
 	ivoc_help("help ?1 calc /home/cluster/aleka/MainPath/Desktop/FSBC_model/Multicompartmental_Biophysical_models/mechanism/x86_64/calc.mod\n");
 hoc_register_limits(_mechtype, _hoc_parm_limits);
 hoc_register_units(_mechtype, _hoc_parm_units);
 }
 static double FARADAY = 96480.0;
 static double R = 8.314;
static int _reset;
static char *modelname = "high threshold calcium current (L-current)";

static int error;
static int _ninits = 0;
static int _match_recurse=1;
static void _modl_cleanup(){ _match_recurse=1;}
static int rates(_threadargsprotocomma_ double);
static int states(_threadargsproto_);
 
static int  states ( _threadargsproto_ ) {
   rates ( _threadargscomma_ v ) ;
   m = m + ( 1.0 - exp ( - dt / tau_m ) ) * ( m_inf - m ) ;
    return 0; }
 
static void _hoc_states(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.;
 states ( _p, _ppvar, _thread, _nt );
 hoc_retpushx(_r);
}
 
double ghk ( _threadargsprotocomma_ double _lv , double _lci , double _lco , double _lz ) {
   double _lghk;
 double _le , _lw ;
 _lw = _lv * ( .001 ) * _lz * FARADAY / ( R * ( celsius + 273.16 ) ) ;
   if ( fabs ( _lw ) > 1e-4 ) {
     _le = _lw / ( exp ( _lw ) - 1.0 ) ;
     }
   else {
     _le = 1.0 - _lw / 2.0 ;
     }
   _lghk = - ( .001 ) * _lz * FARADAY * ( _lco - _lci * exp ( _lw ) ) * _le ;
   
return _lghk;
 }
 
static void _hoc_ghk(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 =  ghk ( _p, _ppvar, _thread, _nt, *getarg(1) , *getarg(2) , *getarg(3) , *getarg(4) );
 hoc_retpushx(_r);
}
 
static int  rates ( _threadargsprotocomma_ double _lv ) {
   double _la , _lb ;
 _la = 1.6 / ( 1.0 + exp ( - 0.072 * ( _lv - 15.0 ) ) ) ;
   _lb = 0.02 * vtrap ( _threadargscomma_ - ( _lv - 1.31 ) , 5.36 / 2.0 ) ;
   tau_m = 1.0 / ( _la + _lb ) / ( tadj * 1.43 ) ;
   m_inf = 1.0 / ( 1.0 + exp ( ( _lv + 9.0 ) / - 6.0 ) ) ;
    return 0; }
 
static void _hoc_rates(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.;
 rates ( _p, _ppvar, _thread, _nt, *getarg(1) );
 hoc_retpushx(_r);
}
 
double vtrap ( _threadargsprotocomma_ double _lx , double _lc ) {
   double _lvtrap;
 if ( fabs ( _lx / _lc ) < 1e-6 ) {
     _lvtrap = _lc + _lx / 2.0 ;
     }
   else {
     _lvtrap = _lx / ( 1.0 - exp ( - _lx / _lc ) ) ;
     }
   
return _lvtrap;
 }
 
static void _hoc_vtrap(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 =  vtrap ( _p, _ppvar, _thread, _nt, *getarg(1) , *getarg(2) );
 hoc_retpushx(_r);
}
 
static int _ode_count(int _type){ hoc_execerror("calc", "cannot be used with CVODE"); return 0;}
 extern void nrn_update_ion_pointer(Symbol*, Datum*, int, int);
 static void _update_ion_pointer(Datum* _ppvar) {
   nrn_update_ion_pointer(_ca_sym, _ppvar, 0, 1);
   nrn_update_ion_pointer(_ca_sym, _ppvar, 1, 2);
   nrn_update_ion_pointer(_ca_sym, _ppvar, 2, 3);
   nrn_update_ion_pointer(_ca_sym, _ppvar, 3, 4);
 }

static void initmodel(double* _p, Datum* _ppvar, Datum* _thread, _NrnThread* _nt) {
  int _i; double _save;{
  m = m0;
 {
   tadj = pow( 3.0 , ( ( celsius - 23.5 ) / 10.0 ) ) ;
   rates ( _threadargscomma_ v ) ;
   m = m_inf ;
   }
 
}
}

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;
  cai = _ion_cai;
  cao = _ion_cao;
 initmodel(_p, _ppvar, _thread, _nt);
 }
}

static double _nrn_current(double* _p, Datum* _ppvar, Datum* _thread, _NrnThread* _nt, double _v){double _current=0.;v=_v;{ {
   ica = gcabar * m * m * ghk ( _threadargscomma_ v , cai , cao , 2.0 ) ;
   }
 _current += ica;

} 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);
  }
  cai = _ion_cai;
  cao = _ion_cao;
 _g = _nrn_current(_p, _ppvar, _thread, _nt, _v + .001);
 	{ double _dica;
  _dica = ica;
 _rhs = _nrn_current(_p, _ppvar, _thread, _nt, _v);
  _ion_dicadv += (_dica - ica)/.001 ;
 	}
 _g = (_g - _rhs)/.001;
  _ion_ica += ica ;
#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;
{
  cai = _ion_cai;
  cao = _ion_cao;
 {  { states(_p, _ppvar, _thread, _nt); }
  } }}

}

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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