Active zones, a term coined by Couteaux and Pecot-Dechavassine (1970), are unanimously defined as the sites located along an axon or in a nerve terminal where neurotransmitter release occurs. Such sites can be readily detected morphologically because clusters of dozens to hundreds of SVs are located close to them. Deep-etch electron microscopic studies have revealed that at central nervous system synapses these SV clusters are embedded in a filamentous meshwork of proteins, which has been termed the presynaptic cytomatrix. Key proteins of the presynaptic cytomatrix are synapsins, peripheral membrane proteins of SVs that are thought to reversibly crosslink SVs and to bind them to actin in a phosphorylation-dependent manner7,9,10. Those SVs of the cluster that appear to touch the plasma membrane at the release site, generally referred to as "docked vesicles," are embedded in an even thicker meshwork of filaments, which is immediately obvious in electron micrographs as an electron-dense thickening of the cytoplasm and the presynaptic plasma membrane. End face views of this area suggest that the electron-dense material is organized like an egg carton with pyramidal projections surrounding depressions that have just about the size to each harbor an SV. As these structures display a more or less regular hexagonal array they were termed "presynaptic grid"7,11-13. Based on ultrastructural observations at the Mauthner cell of teleosts it was hypothesized that the presynaptic grid may undergo activity-dependent deformations and that the release of individual vesicles may lead to distortions in the grid, which in turn limit the release probability for other vesicles14.
Despite agreement on the concept of active zones there are subtle variances in the terminology. For example, active zones are sometimes defined as the "electron-dense, biochemically insoluble material located at the presynaptic plasma membrane precisely opposite the synaptic cleft" and as "the specialized region of the cortical cytoplasm of the presynaptic nerve terminal that directly faces the synaptic cleft"2,3. On the other hand, active zones may be considered as subcellular compartments, including the region of the plasma membrane facing the synaptic cleft plus the underlying dense material and the SVs embedded in it (e.g., ref. 15). For the purpose of this article we employ the latter nomenclature and refer to the specialized dense material specifically as the CAZ7. This notion emphasizes that active zones are functional units promoting regulated and spatially restricted exocytosis of neurotransmitter, and it takes into account that transmembrane proteins and lipids of the active zone plasma membrane, a set of SVs, and the molecules of the CAZ interact with each other to orchestrate regulated neurotransmitter release. Using this notion, the "CAZ" is synonymous with "the presynaptic particle web"16, and "active zones" consist of an area of plasma membrane as well as underlying CAZ material.
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