Two-step docking site model. Monte Carlo simulations were performed to predict synaptic responses to an AP train in a two-step docking model, depending on each kinetic parameter of the model. (A) Scheme describing the two-step model, where a replacement site (red) is associated to each docking site (gray). The replacement site can be either empty or occupied by an SV and has an initial probability of occupancy ρ before a train. If it is empty, it cannot replenish the associated docking site in case of release. If it is occupied, it can supply an SV to the depleted docking site, with a probability of recovery r′ during one interspike interval. Emptied replacement sites are replenished from an infinite SV pool with a transition probability s, again applying for one interspike interval. (B) Simulations examining the evolution of P_D(S_i) as a function of i when each one of the five synaptic parameters is separately incremented from 0 to 1 (color code is violet to red). The other four parameters are kept at reference values (indicated above each plot) mimicking control conditions for MLI–MLI synapses. (C) PPR analysis as a function of individual synaptic parameters. Linear relations are obtained when any of the parameters p (a), r′ (c), ρ (d), or s (e) is examined; in the case of δ (b), the relation is hyperbolic (color-coded dots, simulations; red, regression lines). Reference parameter values are p = 0.95, δ = 0.5, r′ = 0.15, ρ = 0.65, and s = 0.35 and refer to MLI–MLI synapses.