Neurotransmitter Release from Presynaptic Terminals

Abstract Neurotransmitter release from presynaptic nerve terminals is a central component of synaptic transmission, the main process by which neurons communicate with each other and with target cells. Neurotransmitter is packaged inside small vesicles in the presynaptic nerve terminal. When an action potential invades the nerve terminal, voltage‐gated calcium channels open and calcium flows into the cell. The influx of calcium triggers the fusion of the neurotransmitter‐filled synaptic vesicles with the cell membrane, thereby releasing their contents into the synaptic cleft. In addition to action potential‐evoked release, neurotransmitter can also be released ‘spontaneously’ in the absence of action potential firing. Although evoked and spontaneous release share many features, there is growing evidence that they may serve different functions and might be modulated through different signalling pathways, adding richness to the synaptic repertoire. Key Concepts Neurotransmitter release is the main mechanism by which neurons communicate with one another and with muscles—without neurotransmission, we could not sense our environment, think or act. Neurotransmitter release is tightly regulated, and is very rapidly triggered by the firing of an action potential, which depolarises the presynaptic terminal and causes the influx of calcium ions. Neurotransmitter release is probabilistic; only a fraction of action potentials succeed in triggering release of neurotransmitter from any particular release site. Calcium ions are the critical signal that coordinates the molecular interactions responsible for fusion of neurotransmitter‐filled synaptic vesicles with the plasma membrane. Because synaptic vesicles are roughly the same size and contain about the same amount of neurotransmitter, neurotransmitter release can be characterised as ‘quantal’, that is, occurring in discrete packets. Neurotransmitter release can occur through three different mechanisms: fast synchronous, slower asynchronous and spontaneous. Synchronous and asynchronous releases are triggered by action potentials, whereas spontaneous release occurs in the absence of action potential firing. Although synchronous, asynchronous and spontaneous neurotransmitter release share many common features, current evidence suggests that different molecules, signalling pathways and/or vesicle pools might be responsible for mediating and modulating these different forms of neurotransmitter release.