Nanoscale dynamics of synaptic vesicle trafficking and fusion at the presynaptic active zone

Neurons communicate with one another through junctions known as synapses. When a neuron is activated, it triggers the release of chemicals called neurotransmitters at the synapse, which bind to and activate neighbouring neurons. Neurons involved in vision, sound and balance contain “ribbon” synapses, which are able to release neurotransmitters steadily over longer periods of time than other types of synapse. Neurotransmitters inside neurons are packaged into small structures called vesicles, which can then fuse with the cell’s surface membrane to release the neurotransmitters from the cell. Unlike other types of synapse, ribbon synapses are able to release these vesicles in a continuous fashion. How vesicles move around at the synapses remains poorly understood because monitoring the vesicles in living cells is technically difficult and previous studies were limited to tracking vesicles in a small part of the synapse. Now, Vaithianathan et al. overcome these technical hurdles to follow the movement of vesicles across whole ribbon synapses in zebrafish eyes. The experiments use fluorescent proteins to track the movement of the vesicles under a microscope. Vaithianathan et al. find that vesicles at ribbon synapses move very little when the neurons are not active. However, when the neurons are activated, the vesicles that are near the cell membrane fuse with it and release their neurotransmitters. Other vesicles that are further away from the membrane then move to fill in the spaces vacated by the fusing vesicles. Further experiments show that some of the vesicles that are further away from the membrane can fuse with vesicles that have already released their neurotransmitter but remain in place at the membrane. This process – known as compound fusion – allows neurotransmitters to be released over a longer period of time by providing a path for vesicles to release neurotransmitters without having to approach the membrane first. The next challenge is to develop a computational model using the data from this study to better understand how ribbon synapses work.