Soluble membrane trafficking proteins taking a break at silent synaptic vesicles

Abstract

Synaptic nerve terminals are distinguished by clusters of synaptic vesicles that appose active zones in the presynaptic plasma membrane (Fig. 1A). In response to action potentials, vesicles fuse with the plasma membrane to release neurotransmitter, which is followed by vesicle recycling via endocytosis (1). It has long been recognized that subsets of synaptic vesicles within a cluster behave differently (2). One pool, often termed the recycling pool, recycles upon moderate stimulation, and a subfraction of this pool, called the readily releasable pool, is available for immediate release. The remaining vesicles in a cluster are typically reluctant to be released. Such vesicles have been shown, at least in some model systems, to be fully release-competent (2, 3) (Fig. 1B), which has led to the notion that reluctant vesicles serve as a reserve pool that can be recruited during periods of intense neurotransmitter release (2). As yet, however, studies regarding the role of reluctant vesicles have been limited to different in vitro situations. A study in PNAS (4) now makes the move to in vivo conditions by investigating central and peripheral synapses in a variety of animal models, ranging from worm to rat.