COMMENT
/*
Copyright (c) 2015 EPFL-BBP, All rights reserved.
THIS SOFTWARE IS PROVIDED BY THE BLUE BRAIN PROJECT ``AS IS''
AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO,
THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR
PURPOSE ARE DISCLAIMED. IN NO EVENT SHALL THE BLUE BRAIN PROJECT
BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR
CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF
SUBSTITUTE GOODS OR SERVICES; LOSS OF USE, DATA, OR PROFITS; OR
BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY,
WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT (INCLUDING NEGLIGENCE
OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE OF THIS SOFTWARE, EVEN
IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE.
This work is licensed under a
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
To view a copy of this license, visit
http://creativecommons.org/licenses/by-nc-sa/4.0/legalcode or send a letter to
Creative Commons,
171 Second Street, Suite 300,
San Francisco, California, 94105, USA.
*/
ENDCOMMENT
TITLE Probabilistic AMPA and NMDA receptor with presynaptic short-term plasticity
COMMENT
AMPA and NMDA receptor conductance using a dual-exponential profile
presynaptic short-term plasticity as in Fuhrmann et al. 2002
_EMS (Eilif Michael Srikanth)
Modification of ProbAMPANMDA: 2-State model by Eilif Muller, Michael Reimann, Srikanth Ramaswamy, Blue Brain Project, August 2011
This new model was motivated by the following constraints:
1) No consumption on failure.
2) No release just after release until recovery.
3) Same ensemble averaged trace as deterministic/canonical Tsodyks-Markram
using same parameters determined from experiment.
4) Same quantal size as present production probabilistic model.
To satisfy these constaints, the synapse is implemented as a
uni-vesicular (generalization to multi-vesicular should be
straight-forward) 2-state Markov process. The states are
{1=recovered, 0=unrecovered}.
For a pre-synaptic spike or external spontaneous release trigger
event, the synapse will only release if it is in the recovered state,
and with probability u (which follows facilitation dynamics). If it
releases, it will transition to the unrecovered state. Recovery is as
a Poisson process with rate 1/Dep.
This model satisfies all of (1)-(4).
ENDCOMMENT
COMMENT
/**
@file ProbAMPANMDA_EMS.mod
@brief Probabilistic AMPA and NMDA receptor with presynaptic short-term plasticity
@author Eilif Muller, Michael Reimann, Srikanth Ramaswamy, James King @ BBP
@date 2011
*/
ENDCOMMENT
NEURON {
THREADSAFE
POINT_PROCESS ProbAMPANMDA_EMS_group
RANGE tau_r_AMPA, tau_d_AMPA, tau_r_NMDA, tau_d_NMDA, Nsyns
RANGE Use, u, Dep, Fac, u0, mg, Rstate, tsyn_fac, u
RANGE i, i_AMPA, i_NMDA, g_AMPA, g_NMDA, g, e, NMDA_ratio, gmax
RANGE A_AMPA_step, B_AMPA_step, A_NMDA_step, B_NMDA_step
NONSPECIFIC_CURRENT i
POINTER rng
RANGE synapseID, verboseLevel
}
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 release probability
synapseID = 0
verboseLevel = 0
NMDA_ratio = 0.71 (1) : The ratio of NMDA to AMPA
Nsyns = 10
}
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)
g (uS)
factor_AMPA
factor_NMDA
A_AMPA_step
B_AMPA_step
A_NMDA_step
B_NMDA_step
rng
: Recording these three, you can observe full state of model
: tsyn_fac gives you presynaptic times, Rstate gives you
: state transitions,
: u gives you the "release probability" at transitions
: (attention: u is event based based, so only valid at incoming events)
Rstate (1) : recovered state {0=unrecovered, 1=recovered}
tsyn_fac (ms) : the time of the last spike
u (1) : running release probability
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
Rstate=1
tsyn_fac=0
u=u0
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
A_AMPA_step = exp(dt*(( - 1.0 ) / tau_r_AMPA))
B_AMPA_step = exp(dt*(( - 1.0 ) / tau_d_AMPA))
A_NMDA_step = exp(dt*(( - 1.0 ) / tau_r_NMDA))
B_NMDA_step = exp(dt*(( - 1.0 ) / tau_d_NMDA))
}
BREAKPOINT {
SOLVE state
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
g = g_AMPA + g_NMDA
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
}
PROCEDURE state() {
A_AMPA = A_AMPA*A_AMPA_step
B_AMPA = B_AMPA*B_AMPA_step
A_NMDA = A_NMDA*A_NMDA_step
B_NMDA = B_NMDA*B_NMDA_step
}
NET_RECEIVE (weight, Psurv, myInd, tsyn (ms), tsyn_fac (ms), u){
LOCAL result
: Locals:
: Psurv - survival probability of unrecovered state
: tsyn - time since last release (will be saved to &space)
: tsyn_fac - time since last surival evaluation (will be saved to &space)
: u - facilitation variable (will be saved to &space)
INITIAL{
tsyn=t
}
: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[2] = myInd;
_args[3] = x[myInd]; //tsyn
_args[4] = x[myInd+(int)Nsyns]; //tsyn_fac
_args[5] = x[myInd+2*((int)Nsyns)]; //u
ENDVERBATIM
: Do not perform any calculations if the synapse (netcon) is deactivated. This avoids drawing from the random stream
if( !(weight > 0) ) {
VERBATIM
return;
ENDVERBATIM
}
: calc u at event-
if (Fac > 0) {
u = u*exp(-(t - tsyn_fac)/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.
}
: tsyn_fac knows about all spikes, not only those that released
: i.e. each spike can increase the u, regardless of recovered state.
tsyn_fac = t
: recovery
if (Rstate == 0) {
: probability of survival of unrecovered state based on Poisson recovery with rate 1/tau
Psurv = exp(-(t-tsyn)/Dep)
result = urand()
if (result>Psurv) {
Rstate = 1 : recover
if( verboseLevel > 0 ) {
printf( "Recovered! %f at time %g: Psurv = %g, urand=%g\n", synapseID, t, Psurv, result )
}
}
else {
: survival must now be from this interval
tsyn = t
if( verboseLevel > 0 ) {
printf( "Failed to recover! %f at time %g: Psurv = %g, urand=%g\n", synapseID, t, Psurv, result )
}
}
}
if (Rstate == 1) {
result = urand()
if (result<u) {
: release!
tsyn = t
Rstate = 0
A_AMPA = A_AMPA + weight*factor_AMPA
B_AMPA = B_AMPA + weight*factor_AMPA
A_NMDA = A_NMDA + weight*NMDA_ratio*factor_NMDA
B_NMDA = B_NMDA + weight*NMDA_ratio*factor_NMDA
if( verboseLevel > 0 ) {
printf( "Release! %f at time %g: vals %g %g %g %g\n", synapseID, t, A_AMPA, weight, factor_AMPA, NMDA_ratio )
}
}
else {
if( verboseLevel > 0 ) {
printf("Failure! %f at time %g: urand = %g\n", synapseID, t, result )
}
}
}
VERBATIM
x[myInd] = _args[3]; //tsyn
x[myInd+(int)Nsyns] = _args[4]; //tsyn_fac
x[myInd+2*((int)Nsyns)] = _args[5]; //u
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 uniform(1) mode
*/
void** pv = (void**)(&_p_rng);
if( ifarg(1)) {
*pv = nrn_random_arg(1);
} else {
*pv = (void*)0;
}
}
ENDVERBATIM
}
FUNCTION urand() {
VERBATIM
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);
//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
value = scop_random(1)
VERBATIM
}
ENDVERBATIM
urand = value
}
FUNCTION toggleVerbose() {
verboseLevel = 1-verboseLevel
}
PROCEDURE setVec() { : Sets the number of synapses. This should be done only once for each ProbAMPANMDA2_EMS_group,
: 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
}