The readily releasable pool of synaptic vesicles

Abstract

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-torelease sites.

Presynaptic GCaMP expression decreases vesicle release probability at the calyx of Held

“…We estimated the RRP size using the data from 300 Hz depression trains with three different methods: forward extrapolation (EQ plot,) back extrapolation (SMN plot), and the Wesseling and Lo method (WL; Elmqvist & Quastel, ; Kaeser & Regehr, ; Mahfooz et al, ; Neher, ; Schneggenburger et al, ). Estimation of the RRP is still a highly debatable subject, and all of the methods have caveats (Kaeser & Regehr, ; Neher, ). Therefore, we used all three methods to estimate RRP size and probability of release so that our results can be easily compared to existing reports (cf.…”

“…We did not observe any change in RRP size when calculated using SMN or WL (Table , Figures b and b); however, EQ plot showed a significant increase in RRP (Table , Figure g) for GCaMP‐expressing synapses. This result from the EQ plot may be erroneous, as the method is heavily dependent on vesicular release probability, and accuracy is compromised by low P ves (Kaeser & Regehr, ; Neher, ). Notably, GCaMP did not have any effect on maximum replenishment rate (Table , Figure d) or unitary refilling rate (Table , Figure d), suggesting that this GECI does not overtly affect RRP replenishment, which is also Ca 2+ ‐dependent (Alabi & Tsien, ; de Jong & Fioravante, ).…”

Transcellular Nanoalignment of Synaptic Function

“…Exocytosis of synaptic vesicles does not occur evenly spread over the surface of a nerve terminal, but is restricted to small membrane domains and to a subset of vesicles called readily releasable vesicles (Kaeser and Regehr, 2017). These vesicles fuse at active zones, exocytotic areas that are restricted to the presynaptic membrane opposed to the PSD (Couteaux and Pecot-Dechavassine, 1970; Sudhof, 2012).…”

“…Given that fusion is executed within less than a millisecond upon presynaptic depolarization by an action potential (Borst and Sakmann, 1996; Sabatini and Regehr, 1999), rapidly releasable vesicles must be close to their future sites of release. Recent advances in tissue fixation and tissue electron tomography have allowed to precisely determine the number of tightly docked vesicles at hippocampal synapses, and this number is estimated to be 10–15 vesicles per active zone (Imig et al, 2014; Kaeser and Regehr, 2017; Siksou et al, 2009). However, it is possible that not all docked vesicles are releasable, and that some release sites may not be occupied by docked vesicles because docking may be a dynamic, reversible process (Kaeser and Regehr, 2017; Miki et al, 2016; Wang et al, 2016; Zenisek et al, 2000).…”

Regulation of synaptic release‐site Ca2+ channel coupling as a mechanism to control release probability and short‐term plasticity

“…The molecular mechanisms of SV membrane fusion have long been sought after and detailed insights exist showing that this reaction relies on an evolutionarily highly conserved set of proteins. These proteins mediate the association of SVs to the plasma membrane (termed vesicle docking), the functional maturation to a readily releasable state (termed vesicle priming), and their Ca 2+ ‐induced fusion . The respective reactions are conserved in almost all species and synapse types investigated so far, ranging from the invertebrates Caenorhabditis elegans and Drosophila melanogaster to mammals including humans.…”