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 ENDCOMMENT NEURON { POINT_PROCESS ProbAMPANMDA2group RANGE tau_r_AMPA, tau_d_AMPA, tau_r_NMDA, tau_d_NMDA, Nsyns 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 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(). } 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 } BREAKPOINT { SOLVE state METHOD cnexp mggate = 1 / (1 + (mg/4.1 (mM))*exp(0.063 (/mV)*(-v))) 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 } :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); double *x; int nx = vector_instance_px(*vv, &x); int myInd = rand()%((int)Nsyns); _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 ( "R! Pr = %g\n" , Pr ) } else { ::printf("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 (or if _p_rng is always a null pointer). 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 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 }