NSF/SNAP25 protein complexes. Dense accumulations of proteins are present on the cytoplasmic side of the presynaptic plasma membrane. These presynaptic densities represent specialized areas called active zones where synaptic vesicles are docked and where neurotransmitters are released. Active zones are rich in Rab-GTPase docking complexes (see page 35), t-SNAREs and synaptotagmin binding proteins. The vesicle membrane that is added to the presynaptic membrane is retrieved by endocytosis and reprocessed into synaptic vesicles by the smooth-surfaced endoplasmic reticulum (sER) located in the nerve ending. Numerous small mitochondria are also present in the presynaptic  element.
 The synaptic cleft is the 20to 30-nm space that separates the presynaptic neuron from the postsynaptic neuron or target cell, which the neurotransmitter must cross.
 The postsynaptic membrane (postsynaptic component) contains receptor sites with which the neurotransmitter interacts. This component is formed from a portion of the plasma membrane of the postsynaptic neuron (Fig. 12.8) and is characterized by an underlying layer of dense material. This postsynaptic density represents an elaborate complex of interlinked proteins that serve numerous functions such as translation of the neurotransmitter–receptor interaction into an intracellular signal, anchoring of and trafficking neurotransmitter receptors to the plasma membrane, and anchoring various proteins that modulate receptor activity.
Voltage-gated Ca2 channels in the presynaptic membrane regulate transmitter release.
When a nerve impulse reaches the synaptic bouton, the voltage reversal across the membrane produced by the impulse (called depolarization) causes voltage-gated Ca2
FIGURE 12.8 • Electron micrograph of nerve processes in the cerebral cortex. A synapse can be seen in the center of the micrograph, where an axon ending is apposed to a dendrite. The ending of the axon exhibits numerous neurotransmitter-containing synaptic vesicles that appear as circular profiles. The postsynaptic membrane of the dendrite shows a postsynaptic density. A substance of similar density is also present in the synaptic cleft (intercellular space) at the synapse. 76,000. (Courtesy of Drs. George D. Pappas and Virginia Kriho.) channels to open in the plasma membrane of the bouton. The influx of Ca2 from the extracellular space causes the synaptic vesicles to migrate, anchor, and fuse with the presynaptic membrane, thereby releasing the neurotransmitter into the synaptic cleft by exocytosis. Vesicle docking and fusion is mainly driven by the actions of SNARE and synaptotagmin proteins. Alternative to the massive release of neurotransmitter following vesicle fusion is the process of porocytosis, in which vesicles anchored at the active zones release neurotransmitters through a transient pore connecting the lumen of the vesicle with the synaptic cleft. The neurotransmitter then diffuses across the synaptic cleft. At the same time, the presynaptic membrane of the synaptic bouton that released the neurotransmitter quickly forms endocytotic vesicles that return to the endosomal compartment of the bouton for recycling or reloading with neurotransmitter.
The neurotransmitter binds to either transmitter-gated channels or G-protein–coupled receptors on the postsynaptic membrane.