A two-step docking site model predicting different short-term synaptic plasticity patterns.

The strength of synaptic transmission varies during trains of presynaptic action potentials, notably because of the depletion of synaptic vesicles available for release. It has remained unclear why some synapses display depression over time, whereas others facilitate or show a facilitation and depression sequence. Here we compare the predictions of various synaptic models assuming that several docking/release sites are acting in parallel. These models show variation of docking site occupancy during trains of action potentials due to vesicular release and site replenishment, which give rise to changes in synaptic strength. To conform with recent studies, we assume an initial docking site occupancy of <1, thus permitting site occupancy to increase during action potential trains and facilitation to occur. We consider both a standard one-step model and a more elaborate model that assumes a predocked state (two-step model). Whereas the one-step model predicts monotonic changes of synaptic strength during a train, the two-step model allows nonmonotonic changes, including the often-observed facilitation/depression sequence. Both models predict a partitioning of parameter space between initially depressing and facilitating synapses. Using data obtained from interneuron synapses in the cerebellum, we demonstrate an unusual form of depression/facilitation sequence for very high release probability after prolonged depolarization-induced transmitter release. These results indicate a depletion of predocked vesicles in the two-step model. By permitting docking site occupancy to be <1 at rest, and by incorporating a separate predocked state, we reveal that docking site models can be expanded to mimic the large variety of time-dependent changes of synaptic strength that have been observed during action potential trains. Furthermore, the two-step model provides an effective framework to identify the specific mechanisms responsible for short-term changes in synaptic strength.