TITLE AMPA and NMDA receptor with presynaptic short-term plasticity
COMMENT
AMPA and NMDA receptor conductance using a dual-exponential profile
presynaptic short-term plasticity based on Fuhrmann et al. 2002
Implemented by Srikanth Ramaswamy, Blue Brain Project, July 2009
Etay: changed weight to be equal for NMDA and AMPA, gmax accessible in Neuron
Tuomo: Added the group property - each synapse may correspond to a group of synapses.
The activated synapses are determined in advance by setVec2().
ENDCOMMENT
NEURON {
POINT_PROCESS ProbAMPANMDA2groupdet
RANGE tau_r_AMPA, tau_d_AMPA, tau_r_NMDA, tau_d_NMDA, Nsyns, Nevents, eventCounter
RANGE Use, u, Dep, Fac, u0, weight_factor_NMDA
RANGE i, i_AMPA, i_NMDA, g_AMPA, g_NMDA, e, gmax
NONSPECIFIC_CURRENT i, i_AMPA,i_NMDA
POINTER rng
}
PARAMETER {
tau_r_AMPA = 0.2 (ms) : dual-exponential conductance profile
tau_d_AMPA = 1.7 (ms) : IMPORTANT: tau_r < tau_d
tau_r_NMDA = 0.29 (ms) : dual-exponential conductance profile
tau_d_NMDA = 43 (ms) : IMPORTANT: tau_r < tau_d
Use = 1.0 (1) : Utilization of synaptic efficacy (just initial values! Use, Dep and Fac are overwritten by BlueBuilder assigned values)
Dep = 100 (ms) : relaxation time constant from depression
Fac = 10 (ms) : relaxation time constant from facilitation
e = 0 (mV) : AMPA and NMDA reversal potential
mg = 1 (mM) : initial concentration of mg2+
mggate
gmax = .001 (uS) : weight conversion factor (from nS to uS)
u0 = 0 :initial value of u, which is the running value of Use
Nsyns = 10 : How many synapses are there actually (the size of "space" divided by three)
Nevents = 0 : How many events will there be (the size of "space2")
weight_factor_NMDA = 1
}
COMMENT
The Verbatim block is needed to generate random nos. from a uniform distribution between 0 and 1
for comparison with Pr to decide whether to activate the synapse or not
ENDCOMMENT
VERBATIM
#include<stdlib.h>
#include<stdio.h>
#include<math.h>
double nrn_random_pick(void* r);
void* nrn_random_arg(int argpos);
extern int ifarg(int iarg);
extern int vector_capacity(void* vv);
extern void* vector_arg(int iarg);
ENDVERBATIM
ASSIGNED {
v (mV)
i (nA)
i_AMPA (nA)
i_NMDA (nA)
g_AMPA (uS)
g_NMDA (uS)
factor_AMPA
factor_NMDA
rng
space : A pointer to the vector containing the synapse times. Note that the underlying vector should not be touched after initialization by setVec().
space2 : A pointer to the vector containing the event IDs. Note that the underlying vector should not be touched after initialization by setVec2().
eventCounter : An index for space2 (counts the passed events)
}
STATE {
A_AMPA : AMPA state variable to construct the dual-exponential profile - decays with conductance tau_r_AMPA
B_AMPA : AMPA state variable to construct the dual-exponential profile - decays with conductance tau_d_AMPA
A_NMDA : NMDA state variable to construct the dual-exponential profile - decays with conductance tau_r_NMDA
B_NMDA : NMDA state variable to construct the dual-exponential profile - decays with conductance tau_d_NMDA
}
INITIAL{
LOCAL tp_AMPA, tp_NMDA
A_AMPA = 0
B_AMPA = 0
A_NMDA = 0
B_NMDA = 0
tp_AMPA = (tau_r_AMPA*tau_d_AMPA)/(tau_d_AMPA-tau_r_AMPA)*log(tau_d_AMPA/tau_r_AMPA) :time to peak of the conductance
tp_NMDA = (tau_r_NMDA*tau_d_NMDA)/(tau_d_NMDA-tau_r_NMDA)*log(tau_d_NMDA/tau_r_NMDA) :time to peak of the conductance
factor_AMPA = -exp(-tp_AMPA/tau_r_AMPA)+exp(-tp_AMPA/tau_d_AMPA) :AMPA Normalization factor - so that when t = tp_AMPA, gsyn = gpeak
factor_AMPA = 1/factor_AMPA
factor_NMDA = -exp(-tp_NMDA/tau_r_NMDA)+exp(-tp_NMDA/tau_d_NMDA) :NMDA Normalization factor - so that when t = tp_NMDA, gsyn = gpeak
factor_NMDA = 1/factor_NMDA
eventCounter = 0
}
BREAKPOINT {
SOLVE state METHOD cnexp
mggate = 1 / (1 + (mg/4.1 (mM))*exp(0.063 (/mV)*(-v))) :mggate kinetics - Spruston et al. 1995
g_AMPA = gmax*(B_AMPA-A_AMPA) :compute time varying conductance as the difference of state variables B_AMPA and A_AMPA
g_NMDA = gmax*(B_NMDA-A_NMDA) * mggate :compute time varying conductance as the difference of state variables B_NMDA and A_NMDA and mggate kinetics
i_AMPA = g_AMPA*(v-e) :compute the AMPA driving force based on the time varying conductance, membrane potential, and AMPA reversal
i_NMDA = g_NMDA*(v-e) :compute the NMDA driving force based on the time varying conductance, membrane potential, and NMDA reversal
i = i_AMPA + i_NMDA
}
DERIVATIVE state{
A_AMPA' = -A_AMPA/tau_r_AMPA
B_AMPA' = -B_AMPA/tau_d_AMPA
A_NMDA' = -A_NMDA/tau_r_NMDA
B_NMDA' = -B_NMDA/tau_d_NMDA
}
NET_RECEIVE (weight, Pv, Pr, u, myInd, tsyn (ms), Pv_tmp){
:printf("NMDA weight = %g\n", weight_NMDA)
INITIAL{
Pv=1
u=u0
eventCounter=0
}
:Randomize which of the synapses is activated. Note that an additional random number is generated by rand() - this may interfere with the random number order in parallel simulations.
VERBATIM
void** vv = (void**)(&space);
void** vv2 = (void**)(&space2);
double *x;
int nx = vector_instance_px(*vv, &x);
double *x2;
int nx2 = vector_instance_px(*vv2, &x2);
int myInd = 0;
if (eventCounter < nx2) {
myInd = x2[(int)eventCounter];
//printf("eventCounter < nx2. t = %lf, eventCounter = %lf, nx2 = %i, myInd = %i\n",t, eventCounter, nx2, myInd);
}
else printf("eventCounter >= nx2! t = %lf, eventCounter = %lf, nx2 = %i\n",t, eventCounter, nx2);
eventCounter++;
_args[4] = myInd;
_args[5] = x[myInd]; //tsyn
_args[1] = x[myInd+(int)Nsyns]; //Pv
_args[3] = x[myInd+2*((int)Nsyns)]; //u
ENDVERBATIM
::printf("NET_RECEIVE_beg: Pv = %g, Pr = %g, u = %g, myInd = %g, tsyn = %g, t = %g\n", Pv, Pr, u, myInd, tsyn, t)
:printf("NET_RECEIVE_beg: myInd = %g/%g, Pv = %g, u = %g, tsyn = %g, t = %g. ", myInd, Nsyns, Pv, u, tsyn, t)
: calc u at event-
if (Fac > 0) {
u = u*exp(-(t - tsyn)/Fac) :update facilitation variable if Fac>0 Eq. 2 in Fuhrmann et al.
} else {
u = Use
}
if(Fac > 0){
u = u + Use*(1-u) :update facilitation variable if Fac>0 Eq. 2 in Fuhrmann et al.
}
Pv_tmp = 1 - (1-Pv) * exp(-(t-tsyn)/Dep) :Probability Pv for a vesicle to be available for release, analogous to the pool of synaptic
:resources available for release in the deterministic model. Eq. 3 in Fuhrmann et al.
Pr = u * Pv_tmp :Pr is calculated as Pv * u (running value of Use)
Pv_tmp = Pv_tmp - u * Pv_tmp :update Pv as per Eq. 3 in Fuhrmann et al.
:printf("Pv = %g\n", Pv)
:printf("Pr = %g\n", Pr)
if (erand() < Pr){
tsyn = t
Pv = Pv_tmp
A_AMPA = A_AMPA + weight*factor_AMPA
B_AMPA = B_AMPA + weight*factor_AMPA
A_NMDA = A_NMDA + weight*weight_factor_NMDA*factor_NMDA
B_NMDA = B_NMDA + weight*weight_factor_NMDA*factor_NMDA
:::printf("Exc Released! Pr = %g, Pv = %g, u = %g, myInd = %g, tsyn = %g\n", Pr, Pv, u, myInd, tsyn)
::printf("Exc Released!\n")
:printf ( "R! Pr = %g\n" , Pr )
} else {
:::printf("Exc Not released! Pr = %g, Pv = %g, u = %g, myInd = %g, tsyn = %g\n", Pr, Pv, u, myInd, tsyn)
::printf("Exc Not released! value = %g, Pr = %g\n", erand(), Pr )
:printf ( "NR! Pr = %g\n" , Pr )
}
:printf("NET_RECEIVE_end: Pv = %g, Pr = %g, u = %g, myInd = %g, tsyn = %g, t = %g\n", Pv, Pr, u, myInd, tsyn, t)
VERBATIM
x[myInd] = _args[5];
x[myInd+(int)Nsyns] = _args[1];
x[myInd+2*((int)Nsyns)] = _args[3];
ENDVERBATIM
}
PROCEDURE setRNG() {
VERBATIM
{
/**
* This function takes a NEURON Random object declared in hoc and makes it usable by this mod file.
* Note that this method is taken from Brett paper as used by netstim.hoc and netstim.mod
* which points out that the Random must be in negexp(1) mode
*/
void** pv = (void**)(&_p_rng);
if( ifarg(1)) {
*pv = nrn_random_arg(1);
} else {
*pv = (void*)0;
}
}
ENDVERBATIM
}
FUNCTION erand() {
VERBATIM
//FILE *fi;
double value;
if (_p_rng) {
/*
:Supports separate independent but reproducible streams for
: each instance. However, the corresponding hoc Random
: distribution MUST be set to Random.negexp(1)
*/
value = nrn_random_pick(_p_rng);
//fi = fopen("RandomStreamMCellRan4.txt", "w");
//fprintf(fi,"random stream for this simulation = %lf\n",value);
//printf("random stream for this simulation = %lf\n",value);
return value;
}else{
ENDVERBATIM
: the old standby. Cannot use if reproducible parallel sim
: independent of nhost or which host this instance is on
: is desired, since each instance on this cpu draws from
: the same stream
erand = exprand(1)
VERBATIM
}
ENDVERBATIM
:erand = value :This line must have been a mistake in Hay et al.'s code, it would basically set the return value to a non-initialized double value.
:The reason it sometimes works could be that the memory allocated for the non-initialized happened to contain the random value
:previously generated. However, here we commented this line out.
}
PROCEDURE setVec() { : Sets the times of firing of each synapse. This should be done only once for each ProbAMPANMDA2group,
: before the running of the simulation, and the underlying vector should be untouched after that.
VERBATIM
void** vv;
vv = (void**)(&space);
*vv = (void*)0;
if (ifarg(1)) {
*vv = vector_arg(1);
Nsyns = vector_capacity(*vv)/3;
}
ENDVERBATIM
}
PROCEDURE setVec2() { : Sets the IDs of the synapses to fire
VERBATIM
void** vv;
vv = (void**)(&space2);
*vv = (void*)0;
if (ifarg(1)) {
*vv = vector_arg(1);
Nevents = vector_capacity(*vv);
}
ENDVERBATIM
}
PROCEDURE printVec() { : Prints the previous times of firing of each synapse.
VERBATIM
void** vv = (void**)(&space);
double *x;
int nx = vector_instance_px(*vv, &x);
int i1;
for (i1=0; i1<Nsyns;i1++) {
printf("tsyns[%i] = %g, Pv[%i] = %g, u[%i] = %g\n", i1, x[i1], i1, x[i1+(nx/3)], i1, x[i1+2*(nx/3)]);
}
ENDVERBATIM
}
PROCEDURE printVec2() { : Prints the previous times of firing of each synapse.
VERBATIM
void** vv = (void**)(&space2);
double *x;
int nx = vector_instance_px(*vv, &x);
int i1;
for (i1=0; i1<Nevents;i1++) {
printf("%g ", x[i1]);
if (i1%100==99)
printf("\n");
}
ENDVERBATIM
}