How do exo- and endocytosis interact at the presynaptic terminal? Intuitively, we might think that the more synaptic vesicles fuse, the more endocytosis will take place to restock them. A recent paper challenges this idea by showing that endocytosis is actually reduced if release is increased.

Sun et al. recorded exo- and endocytosis at the calyx of Held — a giant brainstem synapse — by measuring presynaptic variations in membrane capacitance (Cm), which changes as a function of membrane area; a fast increase in Cm indicates fusion and a slower decay corresponds to membrane retrieval. They evoked fusion at different stimulation frequencies while measuring Cm. Higher stimulation frequencies led to slower endocytosis, and the net increase in Cm (and therefore in synaptic membrane area) paralleled this effect. So, the number of fused vesicles that are still part of the membrane might directly regulate the endocytic rate. The mechanism by which this regulation occurs is unknown, but this means of controlling vesicle turnover might help to prevent overactivation of the postsynaptic cell.

In a related paper, Waters and Smith reported a similar relationship between vesicle traffic and stimulation frequency at another central synapse. They measured synaptic uptake and release of the fluorescent dye FM1-43 in cultured hippocampal neurons, and found that, when stimulating at 10 Hz, fusion rate was related to the number of labelled (recycling) vesicles at the terminal. By contrast, they failed to see such a direct relationship with a stimulation frequency of 1 Hz. These observations argue that the conventional 'scaling model', which states that synaptic properties such as vesicle number and release probability scale together, might not apply at low firing frequencies.

Although we still lack an understanding of the functional implications of these results, both studies highlight the relevance of vesicle recycling to synaptic efficacy, a field that remains to be explored in detail.