Axon terminal

Axon terminals are specialized to release neurotransmitters very rapidly by exocytosis. Neurotransmitter molecules are packaged into synaptic vesicles called quanta 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 several specialized proteins, such as 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. It forces the vesicle's membrane 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 is transmitted between neurons (A) and neurons (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 constructing 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.