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Christina Joselevitch, David P. Zenisek; Vesicle Transport on the Synaptic Ribbon and Its Role in the Recovery from Synaptic Depression. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4804.
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Short-term synaptic depression is a use-dependent plastic change that affects most synapses and leads to decreased transmission efficiency. It is caused by repetitive stimulation and takes seconds to subside. The scope of this study was to study the influence of vesicle replenishment in this process.
Voltage-clamp recordings of goldfish mixed-input bipolar cells were combined with single-vesicle imaging in TIRF microscopy of the axon terminals loaded with FM1-43. The timing of release events and vesicle arrivals at the membrane were correlated with the onset of voltage stimuli, in order to evaluate how trains of voltage steps change vesicle dynamics. Trains with four interstimulus intervals were used to elicit synaptic depression: 60 ms, 120 ms, 240 ms and 480 ms. Active zones were labeled with a RIBEYE-binding fluorescent peptide in order to correlate release and replenishment with synaptic ribbon sites.
Three types of vesicle behavior were classified: (a) mobile vesicles, which are visible for short periods of time and move freely around the terminal; (b) newly immobilized vesicles, which are trapped near the membrane at active zones for prolonged periods; and (c) released vesicles, which unload their contents at active zones. Only the last two types of event are correlated with membrane potential changes. In response to trains of voltage steps, the number of released vesicles decreased after the first voltage pulse. The number of newly immobilized vesicles at active zones also decreased for 60, 120 and 240 ms interstimulus intervals, but followed closely that of released vesicles for the 480 ms interstimulus interval trains. Not all immobilized vesicles seem to be ready for fusion: in most cases, fusion happened at least 150 ms after immobilization, and around 28% of the immobilized vesicles were not released within the 2.5 s of the experiments.
The replenishment of released vesicles at active zones is a very fast process, but does not compensate for the number of released vesicles completely for very short interstimulus intervals. However, since vesicle replenishment has a much faster time constant than recovery from synaptic depression, it cannot be the sole cause for decreased transmission efficiency after repetitive stimulation. Additional steps may need to take place before docked vesicles can fuse with the cell membrane.
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