Models of short-term plasticity in young and mature synapses indicate a maturation of the reserve pool. (A) Two models were probed for their capability to describe the time-course of depression. (i) The models were fit to the normalized experimental Ai/A1 ratios from young L5PNs by simulating the processes at a single release site under the assumption that all sites are identical. Inset: schemes of model 1 (green) and model 2 (blue), showing Ca2+ channels, vesicles of the RRP and the reserve pool (RepP), that were replenished with Ca2+-independent rate constants. The infinite reserve pool is not shown. Fit parameters: k0 = 4.5 s−1 (green); RepP = 2 * RRP, k1 = 3.6 s−1, k2 = 4.6 s−1 (blue). (ii) Initial 200 ms shown on expanded time scale. (B) As in (A), but for mature L5PNs. Note, that model 1 (green) overestimated the initial depression while model 2 (blue) reproduced the data reliably. Fit parameters: k0 = 4.5 s−1 (green); RepP = 4 * RRP, k1 = 0.9 s−1, k2 = 4.5 s−1 (blue). (C) Quality of fits with model 2 to the data from mature synapses with different RepP sizes per release site. Root-mean square deviations (RMS) between simulations and data were calculated for model fits with the indicated RepP sizes and the smallest RMS value (RMSmin) was subtracted from these values. Note the clear minimum at an RepP size of 4. (D) Schemes illustrating the proposed maturation of the RepP at individual release sites during development from young (left) to mature (right; P/Q-type channels in orange, N-type channels in green, micro- and nanodomains; cf. Bornschein et al., 2019).