Axon terminals (also called synaptic boutons, presynaptic terminals, or end-feet) are distal terminations of the branches of an axon. An axon, also called a nerve fiber, is a long, slender projection of a nerve cell that conducts electrical impulses called action potentials away from the neuron's cell body in order to transmit those impulses to other neurons, muscle cells or glands. In the central nervous system, most presynaptic terminals are actually formed along the axons (en-passant boutons), not at their ends (terminal boutons).
Functionally, the axon terminal converts an electrical signal into a chemical signal. When an action potential arrives at an axon terminal (A), neurotransmitter is released and diffuses across the synaptic cleft. If the postsynaptic cell (B) is also a neuron, neurotransmitter receptors generate a small electrical current that changes the postsynaptic potential. If the postsynaptic cell (B) is a muscle cell (neuromuscular junction), it contracts.
Axon terminals are specialized to release neurotransmitter very rapidly by exocytosis. Neurotransmitter molecules are packaged into synaptic vesicles that cluster beneath the axon terminal membrane on the presynaptic side (A) of a synapse. Some of these vesicles are docked, i.e. connected to the membrane by a number of specialized proteins, the SNARE complex. The incoming action potential activates voltage-gated calcium channels, leading to an influx of calcium ions into the axon terminal. The SNARE complex reacts to these calcium ions and forces the membrane of the vesicle to fuse with the presynaptic membrane, releasing their content into the synaptic cleft within 180 µs of calcium entry. When receptors in the postsynaptic membrane bind this neurotransmitter and open ion channels, information has been transmitted between neuron (A) and neuron (B). To generate an action potential in the postsynaptic neuron, many excitatory synapses must be active at the same time.
Historically, calcium-sensitive dyes were the first tool to quantify the calcium influx into synaptic terminals and to investigate the mechanisms of short-term plasticity. The process of exocytosis can be visualized with pH-sensitive fluorescent proteins (Synapto-pHluorin): Before release, vesicles are acidic and the fluorescence is quenched. Upon release, they are neutralized, generating a brief flash of green fluorescence. Another possibility is to construct a genetically encoded sensor that becomes fluorescent when bound to a specific neurotransmitter, e.g. glutamate. This method is sensitive enough to detect the fusion of a single transmitter vesicle in brain tissue and to measure the release probability at individual synapses.
Research for three decades and major recent advances have provided crucial insights into how neurotransmitters are released by Ca2+ -triggered synaptic vesicle exocytosis, leading to reconstitution of basic steps that underlie Ca2+ -dependent membrane fusion and yielding a model that assigns defined functions for central components of the release machinery.