Axon terminal: Difference between revisions

[[File:Synapse diag1.svg|250px|thumb|An axon terminal (A) is transmitting a signal to neuron B (receiving). Features: ''1.'' [[Mitochondria|Mitochondrion]]. ''2.'' [[Synaptic vesicle]] filled with [[neurotransmitters|neurotransmitter]] molecules. ''3.'' Autoreceptor. ''4.'' [[Synapse|Synaptic cleft]] with neurotransmitter molecules. ''5.''Postsynaptic receptors activated by neurotransmitter (induction of a postsynaptic potential). '''6.''' [[Calcium channel]]. '''7.''' Exocytosis of a vesicle. '''8.''' Recaptured neurotransmitter.]]

'''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 [[Neuron|nerve cell]] that conducts electrical impulses called [[action potential]]s 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 receptor|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]].<ref>{{cite web |title=Axon Terminal |work=Medical Dictionary Online |url=http://www.online-medical-dictionary.org/definitions-a/axon-terminal.html |access-date=February 6, 2013 |archive-url=https://web.archive.org/web/20160304001903/http://www.online-medical-dictionary.org/definitions-a/axon-terminal.html |archive-date=2016-03-04 |url-status=dead }}</ref> Neurotransmitter molecules are packaged into [[synaptic vesicle]]s that cluster beneath the axon terminal membrane on the presynaptic side (A) of a synapse. Some of these vesicles are [[Synaptic vesicle|docked]], i.e. connected to the membrane by a number of specialized proteins, the [[SNARE (protein)|SNARE complex]]. The incoming [[action potential]] activates [[Voltage-gated calcium channel|voltage-gated calcium channels]], leading to an influx of calcium ions into the axon terminal. The [[SNARE (protein)|SNARE complex]] reacts to these calcium ions and forces the membrane of the vesicle to fuse with the [[Cell membrane|presynaptic membrane]], releasing their content into the synaptic cleft within 180 [[microsecond|µs]] of calcium entry.<ref name="Llinás81">{{cite journal | vauthors = Llinás R, Steinberg IZ, Walton K | title = Relationship between presynaptic calcium current and postsynaptic potential in squid giant synapse | journal = Biophysical Journal | volume = 33 | issue = 3 | pages = 323–351 | date = March 1981 | pmid = 6261850 | pmc = 1327434 | doi = 10.1016/S0006-3495(81)84899-0 | bibcode = 1981BpJ....33..323L }}</ref><ref name="Rizo 2018 pp. 1364–1391">{{cite journal | vauthors = Rizo J | title = Mechanism of neurotransmitter release coming into focus | journal = Protein Science | volume = 27 | issue = 8 | pages = 1364–1391 | date = August 2018 | pmid = 29893445 | pmc = 6153415 | doi = 10.1002/pro.3445 | type = Review | quote = 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. }}</ref><ref>{{cite journal | vauthors = Südhof TC, Rizo J | title = Synaptic vesicle exocytosis | journal = Cold Spring Harbor Perspectives in Biology | volume = 3 | issue = 12 | pages = a005637 | date = December 2011 | pmid = 22026965 | pmc = 3225952 | doi = 10.1101/cshperspect.a005637 }}</ref> When receptors in the postsynaptic membrane bind this neurotransmitter and open [[Ligand-gated ion channel|ion channels]], information has been transmitted between neuron (A) and neuron (B). To generate an [[action potential]] in the postsynaptic neuron, many [[Excitatory synapse|excitatory synapses]] must be active at the same time.

Historically, [[Calcium imaging|calcium-sensitive dyes]] were the first tool to quantify the calcium influx into synaptic terminals and to investigate the mechanisms of [[Synaptic plasticity|short-term plasticity]].<ref>{{cite journal | vauthors = Zucker RS, Regehr WG | title = Short-term synaptic plasticity | journal = Annual Review of Physiology | volume = 64 | issue = 1 | pages = 355–405 | date = 2002 | pmid = 11826273 | doi = 10.1146/annurev.physiol.64.092501.114547 }}</ref> 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.<ref>{{cite journal | vauthors = Burrone J, Li Z, Murthy VN | title = Studying vesicle cycling in presynaptic terminals using the genetically encoded probe synaptopHluorin | journal = Nature Protocols | volume = 1 | issue = 6 | pages = 2970–2978 | date = 2006 | pmid = 17406557 | doi = 10.1038/nprot.2006.449 }}</ref> Another possibility is to construct a [[Optogenetic methods to record cellular activity|genetically encoded sensor]] that becomes fluorescent when bound to a specific neurotransmitter, e.g. [[Glutamic acid|glutamate]].<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = An optimized fluorescent probe for visualizing glutamate neurotransmission | journal = Nature Methods | volume = 10 | issue = 2 | pages = 162–170 | date = February 2013 | pmid = 23314171 | pmc = 4469972 | doi = 10.1038/nmeth.2333 }}</ref> 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.<ref>{{cite journal | vauthors = Dürst CD, Wiegert JS, Schulze C, Helassa N, Török K, Oertner TG | title = Vesicular release probability sets the strength of individual Schaffer collateral synapses | journal = Nature Communications | volume = 13 | issue = 1 | pages = 6126 | date = October 2022 | pmid = 36253353 | pmc = 9576736 | doi = 10.1038/s41467-022-33565-6 }}</ref>

*[[Endocytosis]]

*[[Vesicular monoamine transporter]]

*LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite.<ref>{{cite journal | vauthors = Toni N, Buchs PA, Nikonenko I, Bron CR, Muller D | title = LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite | journal = Nature | volume = 402 | issue = 6760 | pages = 421–425 | date = November 1999 | pmid = 10586883 | doi = 10.1038/46574 | s2cid = 205056308 | bibcode = 1999Natur.402..421T }}</ref>