Presynaptic origins of distinct modes of neurotransmitter release

Presynaptic nerve terminals release neurotransmitter synchronously, asynchronously or spontaneously. During synchronous neurotransmission release is precisely coupled to action potentials, in contrast, asynchronous release events show only loose temporal coupling to presynaptic activity whereas spontaneous neurotransmission occurs independent of presynaptic activity. The mechanisms that give rise to this diversity in neurotransmitter release modes are poorly understood. Recent studies have described several presynaptic molecular pathways controlling synaptic vesicle pool segregation and recycling, which in turn may dictate distinct modes of neurotransmitter release. In this article, we review this recent work regarding neurotransmitter release modes and their relationship to synaptic vesicle pool dynamics as well as the molecular machinery that establishes synaptic vesicle pool identity.