Vesicular transporters (VTs) define the type of neurotransmitter that synaptic vesicles (SVs) store and release. While certain neurons in mammalian brain release multiple transmitters, the prevalence, physiology of such pluralism and if the release occurs from same or distinct vesicle pools is not clear. Using quantitative imaging and biochemical approaches, we show that only a small population of neuronal SVs contain different VTs to accomplish corelease. Surprisingly, a highly diverse SV population (27 types) exist that express dual transporters suggesting corelease of diverse combinations of dual neurotransmitters, which includes the vesicle type that contains glutamate and zinc accounting for ∼34% of all SVs. Importantly, we demonstrate that transporter colocalization influences vesicular glutamate uptake leading to enhanced synaptic quantal size. Thus, localization of diverse transporters on single vesicles is bona-fide and the mechanism may underlie regulation of transmitter content, type and release in space and time.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.