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Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8655-60. doi: 10.1073/pnas.1323962111. Epub 2014 May 27.

Visualizing synaptic vesicle turnover and pool refilling driven by calcium nanodomains at presynaptic active zones of ribbon synapses.

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Departments of Neurobiology and Behavior andSUNY Eye Institute, Syracuse, NY 13202.
Departments of Neurobiology and Behavior andSUNY Eye Institute, Syracuse, NY 13202Ophthalmology, Stony Brook University, Stony Brook, NY 11794-5230; and


Ribbon synapses of photoreceptor cells and second-order bipolar neurons in the retina are specialized to transmit graded signals that encode light intensity. Neurotransmitter release at ribbon synapses exhibits two kinetically distinct components, which serve different sensory functions. The faster component is depleted within milliseconds and generates transient postsynaptic responses that emphasize changes in light intensity. Despite the importance of this fast release for processing temporal and spatial contrast in visual signals, the physiological basis for this component is not precisely known. By imaging synaptic vesicle turnover and Ca(2+) signals at single ribbons in zebrafish bipolar neurons, we determined the locus of fast release, the speed and site of Ca(2+) influx driving rapid release, and the location where new vesicles are recruited to replenish the fast pool after it is depleted. At ribbons, Ca(2+) near the membrane rose rapidly during depolarization to levels >10 µM, whereas Ca(2+) at nonribbon locations rose more slowly to the lower level observed globally, consistent with selective positioning of Ca(2+) channels near ribbons. The local Ca(2+) domain drove rapid exocytosis of ribbon-associated synaptic vesicles nearest the plasma membrane, accounting for the fast component of neurotransmitter release. However, new vesicles replacing those lost arrived selectively at the opposite pole of the ribbon, distal to the membrane. Overall, the results suggest a model for fast release in which nanodomain Ca(2+) triggers exocytosis of docked vesicles, which are then replaced by more distant ribbon-attached vesicles, creating opportunities for new vesicles to associate with the ribbon at membrane-distal sites.

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