The readily releasable pool of synaptic vesicles

•Methods to measure RRP are reviewed and their assumptions and limitations discussed.•Action potential trains can be used to measure the physiologically relevant RRP.•Activation of a release site by Munc13 and RIM is necessary for RRP generation.•RRP comprises docked vesicles and rapidly recruited undocked vesicles.•Linking ultrastructure, molecular mechanisms and RRP measurements remains a challenge.

Each presynaptic bouton is densely packed with many vesicles, only a small fraction of which are available for immediate release. These vesicles constitute the readily releasable pool (RRP). The RRP size, and the probability of release of each vesicle within the RRP, together determine synaptic strength. Here, we discuss complications and recent advances in determining the size of the physiologically relevant RRP. We consider molecular mechanisms to generate and regulate the RRP, and discuss the relationship between vesicle docking and the RRP. We conclude that many RRP vesicles are docked, that some docked vesicles may not be part of the RRP, and that undocked vesicles can contribute to the RRP by rapid recruitment to unoccupied, molecularly activated ready-to-release sites.