The presynaptic active zone: A dynamic scaffold that regulates synaptic efficacy

•Recent progress linking presynaptic active zone ultrastructure to function.•Dynamic properties of the active zone.•Role of the active zone in the regulation of synaptic efficacy.

Before fusing with the presynaptic plasma membrane to release neurotransmitter into the synaptic cleft synaptic vesicles have to be recruited to and docked at a specialized area of the presynaptic nerve terminal, the active zone. Exocytosis of synaptic vesicles is restricted to the presynaptic active zone, which is characterized by a unique and highly interconnected set of proteins. The protein network at the active zone is integrally involved in this process and also mediates changes in release properties, for example in response to alterations in the level of neuronal network activity. In recent years the development of novel techniques has greatly advanced our understanding of the molecular identity of respective active zone components as well as of the ultrastructure of this membranous subcompartment and of the SV release machinery. Furthermore, active zones are now viewed as dynamic structures whose composition and size are correlated with synaptic efficacy. Therefore, the dynamic remodeling of the protein network at the active zone has emerged as one potential mechanism underlying acute and long-term synaptic plasticity. Here, we will discuss this recent progress and its implications for our view of the role of the AZ in synaptic function.