Axon terminal explained

Axon terminals (also called synaptic boutons, or presynaptic terminals) 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 to transmit those impulses to other neurons, muscle cells, or glands. Most presynaptic terminals in the central nervous system are 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), the 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.

Neurotransmitter release

Axon terminals are specialized to release neurotransmitters very rapidly by exocytosis.^[1] 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 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.^{[2] [3] [4]} When receptors in the postsynaptic membrane bind this neurotransmitter and open ion channels, information is transmitted between neurons (A) and neurons (B).^[5] To generate an action potential in the postsynaptic neuron, many excitatory synapses must be active at the same time.

Imaging the activity of axon terminals

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.^[6] 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.^[7] Another possibility is constructing a genetically encoded sensor that becomes fluorescent when bound to a specific neurotransmitter, e.g., glutamate.^[8] 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.^[9]

See also

• Calyx of Held, a giant axon terminal in the auditory system
• Neuromuscular junction, axon terminal contacting a muscle cell
• Endocytosis to recycle vesicles after use
• Vesicular monoamine transporter, loading vesicles with neurotransmitter.
• Optogenetic methods to measure cellular activity

Further reading

• Cragg SJ, Greenfield SA . Differential autoreceptor control of somatodendritic and axon terminal dopamine release in substantia nigra, ventral tegmental area, and striatum . The Journal of Neuroscience . 17 . 15 . 5738–5746 . August 1997 . 9221772 . 6573186 . 10.1523/JNEUROSCI.17-15-05738.1997 .
• Vaquero CF, de la Villa P . Localisation of the GABA(C) receptors at the axon terminal of the rod bipolar cells of the mouse retina . Neuroscience Research . 35 . 1 . 1–7 . October 1999 . 10555158 . 10.1016/S0168-0102(99)00050-4 . 53189471 .
• Roffler-Tarlov S, Beart PM, O'Gorman S, Sidman RL . Neurochemical and morphological consequences of axon terminal degeneration in cerebellar deep nuclei of mice with inherited Purkinje cell degeneration . Brain Research . 168 . 1 . 75–95 . May 1979 . 455087 . 10.1016/0006-8993(79)90129-X . 19618884 .
• Yagi T, Kaneko A . The axon terminal of goldfish retinal horizontal cells: a low membrane conductance measured in solitary preparations and its implication to the signal conduction from the soma . Journal of Neurophysiology . 59 . 2 . 482–494 . February 1988 . 3351572 . 10.1152/jn.1988.59.2.482 .
• LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite.Toni N, Buchs PA, Nikonenko I, Bron CR, Muller D . LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite . Nature . 402 . 6760 . 421–425 . November 1999 . 10586883 . 10.1038/46574 . 205056308 . 1999Natur.402..421T .

Notes and References

1. Book: Neuroscience . 2019 . Sinauer Associates / Oxford University Press . 978-1-60535-841-3 . Purves . Dale . 6th . New York . Augustine . George J. . Fitzpatrick . David.
2. Llinás R, Steinberg IZ, Walton K . Relationship between presynaptic calcium current and postsynaptic potential in squid giant synapse . Biophysical Journal . 33 . 3 . 323–351 . March 1981 . 6261850 . 1327434 . 10.1016/S0006-3495(81)84899-0 . 1981BpJ....33..323L .
3. Rizo J . Mechanism of neurotransmitter release coming into focus . Protein Science . 27 . 8 . 1364–1391 . August 2018 . 29893445 . 6153415 . 10.1002/pro.3445 . Review . 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. .
4. Südhof TC, Rizo J . Synaptic vesicle exocytosis . Cold Spring Harbor Perspectives in Biology . 3 . 12 . a005637 . December 2011 . 22026965 . 3225952 . 10.1101/cshperspect.a005637 .
5. Book: Siegelbaum, Steven A. . Principles of neural science . 2021 . McGraw-Hill . 978-1-259-64223-4 . Kandel . Eric R. . 6th . New York . Koester . John D. . Mack . Sarah H..
6. Zucker RS, Regehr WG . Short-term synaptic plasticity . Annual Review of Physiology . 64 . 1 . 355–405 . 2002 . 11826273 . 10.1146/annurev.physiol.64.092501.114547 .
7. Burrone J, Li Z, Murthy VN . Studying vesicle cycling in presynaptic terminals using the genetically encoded probe synaptopHluorin . Nature Protocols . 1 . 6 . 2970–2978 . 2006 . 17406557 . 10.1038/nprot.2006.449 . 29102814 .
8. Marvin JS, Borghuis BG, Tian L, Cichon J, Harnett MT, Akerboom J, Gordus A, Renninger SL, Chen TW, Bargmann CI, Orger MB, Schreiter ER, Demb JB, Gan WB, Hires SA, Looger LL . 6 . An optimized fluorescent probe for visualizing glutamate neurotransmission . Nature Methods . 10 . 2 . 162–170 . February 2013 . 23314171 . 4469972 . 10.1038/nmeth.2333 .
9. Dürst CD, Wiegert JS, Schulze C, Helassa N, Török K, Oertner TG . Vesicular release probability sets the strength of individual Schaffer collateral synapses . Nature Communications . 13 . 1 . 6126 . October 2022 . 36253353 . 9576736 . 10.1038/s41467-022-33565-6 .