Fig. 3: Models for the spatial organization of asynchronous neurotransmitter release at a synapse.

While the segregation of synchronous and spontaneous release is increasingly understood, the precise location of asynchronous release within the active zone remains highly debated. Left: One hypothesis proposes a center-surround organization among evoked release modes, where fast, synchronous release (Sync) is confined to central release sites, while the more delayed asynchronous release (Async) occurs in the surrounding periphery. Right: An alternative model suggests that both synchronous and asynchronous release are co-localized within central release sites, while spontaneous release (Spont) is segregated to the periphery. This model is supported by findings that asynchronous and synchronous release activate the same NMDA receptors [83], implying a shared location within the active zone center, a conclusion consistent with reports of asynchronous events being biased toward this central region.