synaptic terminal. At the terminal (2) the vesicle is filled with neurotransmitter. (3) The vesicle is transported to the active zone and docked in close proximity to the plasma membrane. (4) During an action potential the vesicle is fused with the membrane, releases the neurotransmitter and allows the membrane proteins previously on the vesicle to diffuse to the periactive zone. (5) In the periactive zone the membrane proteins are sequestered and are endocytosed forming a clathrin coated vesicle. (6) The vesicle is then filled with neurotransmitter and is then transported back to the active zone. The endocytosis mechanism is slower than the exocytosis mechanism. This means that in intense activity the vesicle in the terminal can become depleted and no longer available to be released. To help prevent the depletion of synaptic vesicles the increase in calcium during intense activity can activate calcineurin which dephosphorylate proteins involved in clathrin-mediated endocytosis. Vesicle pools The synapse contains at least two clusters of synaptic vesicles, the readily releasable pool and the reserve pool. The readily releasable pool is located within the active zone and connected directly to the presynaptic membrane while the reserve pool is clustered by cytoskeletal and is not directly connected to the active zone. Releasable pool The releasable pool is located in the active zone and is bound directly to the presynaptic membrane. It is stabilized by proteins within the active zone and bound to the presynaptic membrane by SNARE proteins. These vesicles are ready to release by a single action potential and are replenished by vesicles from the reserve pool. The releasable pool is sometimes subdivided into the readily releasable pool and the releasable pool. Reserve pool The reserve pool is not directly connected to the active zone. The increase in presynaptic calcium concentration activates calcium–calmodulin-dependent protein kinase (CaMK). CaMK phosphorylates a protein, synapsin, that mediates the clustering of the reserve pool vesicles and attachment to the cytoskeleton. Phosphorylation of synapsin mobilizes vesicles in the reserve pool and allows them to migrate to the active zone and replenish the readily releasable pool. Periactive zone The periactive zone surrounds the active zone and is the site of endocytosis of the presynaptic terminal. In the periactive zone, scaffolding proteins such as intersectin 1 recruit proteins that mediate endocytosis such as dynamin, clathrin and endophilin. In Drosophila the intersectin homolog, Dap160, is located in the periactive zone of the neuromuscular junction and