Mechanisms of synaptic vesicle recycling illuminated by fluorescent dyes

The recycling of synaptic vesicles in nerve terminals involves multiple ste ps, underlies all aspects of synaptic transmission, and is a key to underst anding the basis of synaptic plasticity. The development of styryl dyes as fluorescent molecules that label recycling synaptic vesicles has revolution ized the way in which synaptic vesicle recycling can be investigated, by al lowing an examination of processes in neurons that have long been inaccessi ble. In this review, we evaluate the major aspects of synaptic vesicle recy cling that have been revealed and advanced by studies with styryl dyes, foc ussing upon synaptic vesicle fusion, retrieval, and trafficking. The greate st impact of styryl dyes has been to allow the routine visualization of end ocytosis in central nerve terminals for the first time. This has revealed t he kinetics of endocytosis, its underlying sequential steps, and its regula tion by Ca2+. In studies of exocytosis, styryl dyes have helped distinguish between different modes of vesicle fusion, provided direct support for the quantal nature of exocytosis and endocytosis, and revealed how the probabi lity of exocytosis varies enormously from one nerve terminal to another. Sy naptic vesicle labelling with styryl dyes has helped our understanding of v esicle trafficking by allowing better under-standing of different synaptic vesicle pools within the nerve terminal, vesicle intermixing, and vesicle c lustering at release sites. Finally, the dyes are now being used in innovat ive ways to reveal further insights into synaptic plasticity.