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.

Keywords: calcium; exocytosis; membrane fusion; neurotransmitter receptor; synaptic function; synaptic vesicle

Figure 1. Close‐up schematic view of a chemical synapse. Only membrane‐bound organelles are indicated. Neurotransmitter is stored in synaptic vesicles (small green circles) at the presynaptic nerve terminal (top part). The vesicles are clustered in the vicinity of the plasma membrane. A docking step moves vesicles to the membrane where there might be additional reactions required, called priming, before the vesicle can fuse upon calcium (yellow) entry. The vesicle membrane is retrieved via endocytosis and recycled back into the cluster. Dashed grey arrows indicate alternate endocytic pathways. A similar recycling of vesicles has been postulated in the postsynaptic compartment (bottom part) where neurotransmitter receptors are inserted and retrieved as one mechanism to regulate synaptic strength.
Figure 2. Upon fusion of the vesicle with the plasma membrane, the two membranes become continuous, thus creating a pathway for the transmitter to escape into the synaptic cleft.
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References

Alabi AA and Tsien RW (2013) Perspectives on kiss‐and‐run: role in exocytosis, endocytosis, and neurotransmission. Annual Review of Physiology 75: 393–422.

Chapman ER (2008) How does synaptotagmin trigger neurotransmitter release? Annual Review of Biochemistry 77: 615–641.

Kaeser PS and Regehr WG (2014) Molecular mechanisms for synchronous, asynchronous, and spontaneous neurotransmitter release. Annual Review of Physiology 76: 333–363.

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Kavalali ET, Chung C, Khvotchev M, et al. (2011) Spontaneous neurotransmission: an independent pathway for neuronal signaling? Physiology 26: 45–53.

Kochubey O, Lou X and Schneggenburger R (2011) Regulation of transmitter release by Ca(2+) and synaptotagmin: insights from a large CNS synapse. Trends in Neurosciences 34: 237–246.

Ramirez DM and Kavalali ET (2011) Differential regulation of spontaneous and evoked neurotransmitter release at central synapses. Current Opinion in Neurobiology 21: 275–282.

Südhof TC (2013) Neurotransmitter release: the last millisecond in the life of a synaptic vesicle. Neuron 80: 675–690.

Further Reading

Cowan WM, Südhof TC and Stevens CF (eds) (2001) Synapses. Baltimore, MD: Johns Hopkins University Press.

Kandel ER, Schwartz JH, Jessell TM, Siegelbaum SA and Hudspeth AJ (2013) Principles of Neural Science. New York, NY: McGraw‐Hill.

Nicholls JG, Martin AR, Wallace BG, et al. (2011) From Neuron to Brain. Sunderland, MA: Sinauer Associates.

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How to Cite close
Sullivan, Jane M, and Schweizer, Felix E(Jan 2015) Neurotransmitter Release from Presynaptic Terminals. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000285.pub2]