As shown in the adjacent diagram, a synapse consists of the presynaptic bouton of one neuron which stores vesicles containing neurotransmitter (uppermost in the picture), and a second, postsynaptic neuron which bears receptors for the neurotransmitter (at the bottom), together with a gap between the two called the synaptic cleft (with synaptic adhesion molecules, SAMs, holding the two together[1]).

When an action potential reaches the presynaptic bouton, the contents of the vesicles are released into the synaptic cleft and the released neurotransmitter travels across the cleft to the postsynaptic neuron (the lower structure in the picture) and activates the receptors on the postsynaptic membrane.

The increase in calcium is detected by proteins in the active zone and forces vesicles containing neurotransmitter to fuse with the membrane.

The neurotransmitters then diffuse across the cleft and bind to ligand gated ion channels and G-protein coupled receptors on the postsynaptic membrane.

The protein dense projections vary in size and shape depending on the type of synapse examined.

One striking example of the dense projection is the ribbon synapse (see below) which contains a "ribbon" of protein dense material that is surrounded by a halo of synaptic vesicles and extends perpendicular to the presynaptic membrane and can be as long as 500 nm.

[3] The glutamate synapse contains smaller pyramid like structures that extend about 50 nm from the membrane.

[6] There are at least five major scaffold proteins that are enriched in the active zone; UNC13B/Munc13, RIMS1 (Rab3-interacting molecule), Bassoon, Piccolo/aczonin, ELKS, and liprins-α.

[7] β-neurexin then binds to cell adhesion molecule, neuroligin located on the postsynaptic membrane.

One prevailing model of synaptic vesicle fusion is that SNARE complex formation is catalyzed by the proteins of the active zone such as Munc18, Munc13, and RIM.

The arrival of an action potential opens voltage gated calcium channels near the SNARE/complexin complex.

(3) The vesicle is transported to the active zone and docked in close proximity to the plasma membrane.

(5) In the periactive zone the membrane proteins are sequestered and are endocytosed forming a clathrin coated vesicle.

The releasable pool is located in the active zone and is bound directly to the presynaptic membrane.

CaMK phosphorylates a protein, synapsin, that mediates the clustering of the reserve pool vesicles and attachment to the cytoskeleton.

[17] In Drosophila the intersectin homolog, Dap160, is located in the periactive zone of the neuromuscular junction and mutant Dap160 deplete synaptic vesicles during high frequency stimulation.

Ribbon synapses contain a dense protein structure that tethers an array of vesicles perpendicular to the presynaptic membrane.