![Figure 1. Simple docking site model of release probability during train stimulation. Monte Carlo simulations were performed to predict the evolution of the vesicular release probability (PD[Si]) at one docking site during AP trains, as a function of stimulation number, i. (A) Schematic representation of one-step release model on a synapse with a single active zone (gray) and associated postsynaptic receptors (red). Synaptic vesicles (light gray) are recruited from an infinite reserve pool, and just one is bound to a docking site (black) before exocytosis. Here a single docking site is represented, but in reality, simple synapses contain variable docking site numbers, on a range varying from 1 to 6 for MLI–MLI synapses. Reference values for the parameters of the model are similar to values previously obtained at MLI–MLI synapses (Pulido et al., 2015): the docking site occupancy is δ = 0.5 before the train stimulation; the probability of release of a docked vesicle in response to an AP is p = 0.95; and after release, an emptied docking site is replenished from an infinite vesicle pool with a fixed transition probability r = 0.15, estimated over one interstimulus interval (stimulation frequency is 25 Hz). (B) The evolution of PD(Si) as a function of i was examined when synaptic parameters p, δ, and r were separately incremented from 0 to 1 (color code is violet to red, with 0.05 increments for each parameter). (C) PPR plots as a function of each of the three synaptic parameters show that PPR values follow a decreasing linear dependence on p and a decreasing hyperbolic dependence on δ and follow an increasing linear dependence on r (color-coded dots, simulations; red traces, model predictions from Eq. 5). Changing any of the three parameters p, δ, or r allows shifting from a depressing synapse (PPR < 1) to a potentiating synapse (PPR > 1; PPR = 1 indicated by dotted lines). (D) PPR as a function of PD(S1) in the three conditions where each synaptic parameter is modified. In B–D, modified parameters are (a) p (with predictions for the special case where r is very small shown in black), (b) δ, and (c) r. In each case, the remaining parameters are kept at their reference values.](https://cdn.rupress.org/rup/content_public/journal/jgp/150/8/10.1085_jgp.201812072/6/jgp_201812072_fig1.jpeg?Expires=1767810775&Signature=TicuBSaKvdDLVBJJuy2ILAGapw46Tc97UUpf8zaYHZLN-TTqlCPaHlvgb2cG~Hj6BtZ5uKjYrjy5ofrHRlsyCTBFrdgUP3OzHXNOk5o3iIUfrxwoaf9Gv-8UpCsJH8bj69jUosvHA9omE0~VoceFxuN6OAAlgHaeH21nBhYOIL-nOx6ADRj048WFco59IM0IR9YwzjIPSb6~JxcBlGEdyFJyFtoLeLIitb3soFI6AcCKtqEeD1GnpRefEjDiz7TK4vlMJf7QXCwWIzvcmeB8gT7e23uln6PXPnowjp45rhx8e4kGzZdWloq3V48xM~gxu6z5Q9ijHKQX2oYmfd~h6Q__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Simple docking site model of release probability during train stimulation. Monte Carlo simulations were performed to predict the evolution of the vesicular release probability (PD[Si]) at one docking site during AP trains, as a function of stimulation number, i. (A) Schematic representation of one-step release model on a synapse with a single active zone (gray) and associated postsynaptic receptors (red). Synaptic vesicles (light gray) are recruited from an infinite reserve pool, and just one is bound to a docking site (black) before exocytosis. Here a single docking site is represented, but in reality, simple synapses contain variable docking site numbers, on a range varying from 1 to 6 for MLI–MLI synapses. Reference values for the parameters of the model are similar to values previously obtained at MLI–MLI synapses (Pulido et al., 2015): the docking site occupancy is δ = 0.5 before the train stimulation; the probability of release of a docked vesicle in response to an AP is p = 0.95; and after release, an emptied docking site is replenished from an infinite vesicle pool with a fixed transition probability r = 0.15, estimated over one interstimulus interval (stimulation frequency is 25 Hz). (B) The evolution of PD(Si) as a function of i was examined when synaptic parameters p, δ, and r were separately incremented from 0 to 1 (color code is violet to red, with 0.05 increments for each parameter). (C) PPR plots as a function of each of the three synaptic parameters show that PPR values follow a decreasing linear dependence on p and a decreasing hyperbolic dependence on δ and follow an increasing linear dependence on r (color-coded dots, simulations; red traces, model predictions from Eq. 5). Changing any of the three parameters p, δ, or r allows shifting from a depressing synapse (PPR < 1) to a potentiating synapse (PPR > 1; PPR = 1 indicated by dotted lines). (D) PPR as a function of PD(S1) in the three conditions where each synaptic parameter is modified. In B–D, modified parameters are (a) p (with predictions for the special case where r is very small shown in black), (b) δ, and (c) r. In each case, the remaining parameters are kept at their reference values.
