PT - JOURNAL ARTICLE AU - Nathalie Lavoie AU - Danny V. Jeyaraju AU - Modesto R. Peralta III AU - László Seress AU - Luca Pellegrini AU - Katalin Tóth TI - Vesicular Zinc Regulates the Ca<sup>2+</sup> Sensitivity of a Subpopulation of Presynaptic Vesicles at Hippocampal Mossy Fiber Terminals AID - 10.1523/JNEUROSCI.4164-11.2011 DP - 2011 Dec 14 TA - The Journal of Neuroscience PG - 18251--18265 VI - 31 IP - 50 4099 - http://www.jneurosci.org/content/31/50/18251.short 4100 - http://www.jneurosci.org/content/31/50/18251.full SO - J. Neurosci.2011 Dec 14; 31 AB - Synaptic vesicles segregate into functionally diverse subpopulations within presynaptic terminals, yet there is no information about how this may occur. Here we demonstrate that a distinct subgroup of vesicles within individual glutamatergic, mossy fiber terminals contain vesicular zinc that is critical for the rapid release of a subgroup of synaptic vesicles during increased activity in mice. In particular, vesicular zinc dictates the Ca2+ sensitivity of release during high-frequency firing. Intense synaptic activity alters the subcellular distribution of zinc in presynaptic terminals and decreases the number of zinc-containing vesicles. Zinc staining also appears in endosomes, an observation that is consistent with the preferential replenishment of zinc-enriched vesicles by bulk endocytosis. We propose that functionally diverse vesicle pools with unique membrane protein composition support different modes of transmission and are generated via distinct recycling pathways.