Axon terminal: Difference between revisions
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Millencolin (talk | contribs) A rewrite, also added some references to classic papers. Reduced the monomaniacal focus on Wade Regehr. |
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[[File:Synapse diag1.svg|250px|thumb| |
[[File:Synapse diag1.svg|250px|thumb| axon terminal A is transmitting a signal to neuron B (receiving). Features: ''1.'' [[Mitochondria|Mitochondrion]]. ''2.'' [[Synaptic vesicle]] with [[neurotransmitters]] ''3.'' Autoreceptor. ''4.'' [[Synapse]] with neurotransmitter . ''5.''Postsynaptic receptors activated by neurotransmitter (induction of a postsynaptic potential). '''6.''' [[Calcium channel]]. '''7.''' Exocytosis of a vesicle. '''8.''' Recaptured neurotransmitter.]] |
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'''Axon terminals''' (also called '''synaptic boutons |
'''Axon terminals''' (also called '''synaptic boutons, ''', 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 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. |
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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. |
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Neurons are interconnected in complex arrangements, and use electrochemical signals and [[neurotransmitter]] chemicals to transmit impulses from one neuron to the next; axon terminals are separated from neighboring neurons by a small gap called a [[synapse]], across which impulses are sent. The axon terminal, and the neuron from which it comes, is sometimes referred to as the "presynaptic" neuron. |
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== release== |
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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 |date=March 1981 |title=Relationship between presynaptic calcium current and postsynaptic potential in squid giant synapse |journal=Biophysical Journal |volume=33 |issue=3 |pages=323–51 |bibcode=1981BpJ....33..323L |doi=10.1016/S0006-3495(81)84899-0 |pmc=1327434 |pmid=6261850}}</ref><ref name="Rizo 2018 pp. 1364–1391">{{cite journal |last=Rizo |first=Josep |date=2018-07-10 |title=Mechanism of neurotransmitter release coming into focus |journal=Protein Science |type=Review |volume=27 |issue=8 |pages=1364–1391 |doi=10.1002/pro.3445 |issn=0961-8368 |pmc=6153415 |pmid=29893445 |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 |date=December 2011 |title=Synaptic vesicle exocytosis |journal=Cold Spring Harbor Perspectives in Biology |volume=3 |issue=12 |pages=a005637 |doi=10.1101/cshperspect.a005637 |pmc=3225952 |pmid=22026965}}</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. |
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Neurotransmitters are packaged into [[synaptic vesicle]]s that cluster beneath the axon terminal membrane on the presynaptic side of a synapse. The axonal terminals are specialized to release the neurotransmitters of the presynaptic cell.<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> The terminals release transmitter substances into a gap called the [[Chemical synapse|synaptic cleft]] between the terminals and the dendrites of the next neuron. The information is received by the dendrite receptors of the postsynaptic cell that are connected to it. Neurons don't touch each other, but communicate across the synapse.<ref>{{cite web|last=Foster|first=Sally|title=Axon Terminal - Synaptic Vesicle - Neurotransmitter|url=https://www.miracosta.edu/home/sfoster/neurons/axonterminal.htm|access-date=February 6, 2013}}</ref> |
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==Imaging the activity of axon terminals== |
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The neurotransmitter molecule packages (vesicles) are created within the neuron, then travel down the axon to the distal axon terminal where they sit ''[[Exocytosis#Vesicle docking|docked]]''. Calcium ions then trigger a biochemical cascade which results in vesicles fusing with the presynaptic membrane and releasing their contents to 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 = 323–51 | date = March 1981 | pmid = 6261850 | pmc = 1327434 | doi = 10.1016/S0006-3495(81)84899-0 | bibcode = 1981BpJ....33..323L }}</ref> Triggered by the binding of the calcium ions, the synaptic vesicle proteins begin to move apart, resulting in the creation of a [[fusion pore]]. The presence of the pore allows for the release of neurotransmitter into the synaptic cleft.<ref>[https://books.google.com/books?id=xnK5_R_jeboC&q=Carlson+Biology+book Carlson], 2007, p.56</ref><ref>{{cite web|date=November 24, 2011|title=Neuroscience for kids Neurotransmitters and Neuroactive Peptides|url=http://faculty.washington.edu/chudler/chnt1.html|url-status=live|archive-url=https://web.archive.org/web/20081218122223/http://faculty.washington.edu/chudler/chnt1.html|archive-date=December 18, 2008|access-date=February 6, 2013|vauthors=Chudler EH}}</ref> The process occurring at the axon terminal is [[exocytosis]],<ref name="Rizo 2018 pp. 1364–1391">{{cite journal | last=Rizo | first=Josep | title=Mechanism of neurotransmitter release coming into focus | journal=Protein Science | volume=27 | issue=8 | date=2018-07-10 | issn=0961-8368 | pmid=29893445 | pmc=6153415 | doi=10.1002/pro.3445 | pages=1364–1391 | 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. | type=Review}}</ref> which a cell uses to exude secretory [[Vesicle (biology)|vesicles]] out of the [[cell membrane]]. These membrane-bound vesicles contain soluble [[proteins]] to be secreted to the extracellular environment, as well as [[membrane proteins]] and [[lipids]] that are sent to become components of the cell membrane. Exocytosis in neuronal [[chemical synapse]]s is Ca<sup>2+</sup> triggered and serves interneuronal signalling.<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> |
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==Mapping activity== |
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{{Neuron map}} |
{{Neuron map}} |
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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 |last=Zucker |first=Robert S. |last2=Regehr |first2=Wade G. |date=2002 |title=Short-Term Synaptic Plasticity |url=https://www.annualreviews.org/doi/10.1146/annurev.physiol.64.092501.114547 |journal=Annual Review of Physiology |language=en |volume=64 |issue=1 |pages=355–405 |doi=10.1146/annurev.physiol.64.092501.114547 |issn=0066-4278}}</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 |last=Burrone |first=Juan |last2=Li |first2=Zhiying |last3=Murthy |first3=Venkatesh N |date=2006 |title=Studying vesicle cycling in presynaptic terminals using the genetically encoded probe synaptopHluorin |url=https://www.nature.com/articles/nprot.2006.449 |journal=Nature Protocols |language=en |volume=1 |issue=6 |pages=2970–2978 |doi=10.1038/nprot.2006.449 |issn=1754-2189}}</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 |last=Marvin |first=Jonathan S |last2=Borghuis |first2=Bart G |last3=Tian |first3=Lin |last4=Cichon |first4=Joseph |last5=Harnett |first5=Mark T |last6=Akerboom |first6=Jasper |last7=Gordus |first7=Andrew |last8=Renninger |first8=Sabine L |last9=Chen |first9=Tsai-Wen |last10=Bargmann |first10=Cornelia I |last11=Orger |first11=Michael B |last12=Schreiter |first12=Eric R |last13=Demb |first13=Jonathan B |last14=Gan |first14=Wen-Biao |last15=Hires |first15=S Andrew |date=2013 |title=An optimized fluorescent probe for visualizing glutamate neurotransmission |url=https://www.nature.com/articles/nmeth.2333 |journal=Nature Methods |language=en |volume=10 |issue=2 |pages=162–170 |doi=10.1038/nmeth.2333 |issn=1548-7091 |pmc=PMC4469972 |pmid=23314171}}</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 |last=Dürst |first=Céline D. |last2=Wiegert |first2=J. Simon |last3=Schulze |first3=Christian |last4=Helassa |first4=Nordine |last5=Török |first5=Katalin |last6=Oertner |first6=Thomas G. |date=2022-10-17 |title=Vesicular release probability sets the strength of individual Schaffer collateral synapses |url=https://www.nature.com/articles/s41467-022-33565-6 |journal=Nature Communications |language=en |volume=13 |issue=1 |doi=10.1038/s41467-022-33565-6 |issn=2041-1723 |pmc=PMC9576736 |pmid=36253353}}</ref> |
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[[Wade Regehr]], a [[Professor]] of [[Neurobiology]] at [[Harvard Medical School]]'s [[Department of Neurobiology, Harvard Medical School|Department of Neurobiology]], developed a method to physiologically see the synaptic activity that occurs in the brain. A dye alters the fluorescence properties when attached to calcium. Using [[Fluorescence microscope|fluorescence-microscopy]] techniques calcium levels are detected, and therefore the influx of calcium in the [[Chemical synapse|presynaptic neuron]].<ref name="Sauber"> |
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{{cite web | vauthors = Sauber C | title = Focus October 20-Neurobiology VISUALIZING THE SYNAPTIC CONNECTION | url = http://focus.hms.harvard.edu/1995/Oct20_1995/Neurobiology.html | archive-url=https://web.archive.org/web/20060901164942/http://focus.hms.harvard.edu/1995/Oct20_1995/Neurobiology.html | archive-date=2006-09-01 |
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|url-status=dead |access-date=July 3, 2013}}</ref> Regehr's laboratory specializes in pre-synaptic calcium dynamics which occurs at the axon terminals. Regehr studies the implication of [[calcium]] Ca<sup>2+</sup> as it affects synaptic strength.<ref name="Wade"> |
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{{cite web | vauthors = Regehr W |date=1999–2008 |url=http://www.hms.harvard.edu/dms/neuroscience/fac/regehr.html |
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|title=Wade Regehr, Ph.D. |url-status=dead |access-date=July 3, 2013 |archive-url=https://web.archive.org/web/20100218060905/http://www.hms.harvard.edu/dms/neuroscience/fac/Regehr.html |archive-date=February 18, 2010 |
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}}</ref>{{self-published inline|date=February 2013}}<ref name="Regehr">{{cite web | last = President and Fellows of Harvard College | title = The Neurobiology Department at Harvard Medical School | year = 2008 | url = http://neuro.med.harvard.edu/faculty/regehr.html | archive-url = https://web.archive.org/web/20081220175022/http://neuro.med.harvard.edu/faculty/regehr.html | archive-date = 20 December 2008 | url-status = dead | access-date = July 3, 2013 }}</ref> By studying the physiological process and mechanisms, a further understanding is made of neurological disorders such as [[epilepsy]], [[schizophrenia]] and [[major depressive disorder]], as well as [[memory]] and [[learning]].<ref>{{cite press release |title=NINDS Announces New Javits Neuroscience Investigator Awardees |publisher=[[National Institute of Neurological Disorders and Stroke]] |date=May 4, 2005 | url= http://www.ninds.nih.gov/news_and_events/news_articles/news_article_javits_200505.htm |access-date=February 6, 2013 |archive-url= https://web.archive.org/web/20090117120348/http://www.ninds.nih.gov/news_and_events/news_articles/news_article_javits_200505.htm |archive-date=January 17, 2009 |url-status=live}}</ref><ref>{{cite web | title = Scholar Awards | publisher = The McKnight Endowment Fund for Neuroscience | url = http://www.mcknight.org/neuroscience/awardee/scholar_awards.aspx |url-status=dead |archive-url=https://web.archive.org/web/20040508184636/http://www.mcknight.org/neuroscience/awardee/scholar_awards.aspx |archive-date=2004-05-08 |access-date=July 3, 2013 }}</ref> |
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== See also == |
== See also == |
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*[[Endoplasmic reticulum]] |
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*[[Golgi apparatus]] |
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*[[Micelle]] |
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*[[Membrane nanotube]] |
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*[[Endocytosis]] |
*[[Endocytosis]] |
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*[[Vesicular monoamine transporter]] |
*[[Vesicular monoamine transporter]] |
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*[[Optogenetic methods to record cellular activity|Optogenetic methods to measure cellular activity]] |
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== Further reading == |
== Further reading == |
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Revision as of 17:17, 22 August 2023
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 nerve cell that conducts electrical impulses called action potentials 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 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 neurotransmitter 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 a number of specialized proteins, 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 and forces the membrane of the vesicle 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 has been transmitted between neuron (A) and neuron (B). 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
Structure of a typical neuron
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.[5] 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.[6] Another possibility is to construct a genetically encoded sensor that becomes fluorescent when bound to a specific neurotransmitter, e.g. glutamate.[7] 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.[8]
See also
Further reading
- Cragg SJ, Greenfield SA (August 1997). "Differential autoreceptor control of somatodendritic and axon terminal dopamine release in substantia nigra, ventral tegmental area, and striatum". The Journal of Neuroscience. 17 (15): 5738–46. doi:10.1523/JNEUROSCI.17-15-05738.1997. PMC 6573186. PMID 9221772.
- Vaquero CF, de la Villa P (October 1999). "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. doi:10.1016/S0168-0102(99)00050-4. PMID 10555158. S2CID 53189471.
- Roffler-Tarlov S, Beart PM, O'Gorman S, Sidman RL (May 1979). "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. doi:10.1016/0006-8993(79)90129-X. PMID 455087. S2CID 19618884.
- Yagi T, Kaneko A (February 1988). "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): 482–94. doi:10.1152/jn.1988.59.2.482. PMID 3351572.
- LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite.[9]
References
- ^ "Axon Terminal". Medical Dictionary Online. Archived from the original on 2016-03-04. Retrieved February 6, 2013.
- ^ Llinás R, Steinberg IZ, Walton K (March 1981). "Relationship between presynaptic calcium current and postsynaptic potential in squid giant synapse". Biophysical Journal. 33 (3): 323–51. Bibcode:1981BpJ....33..323L. doi:10.1016/S0006-3495(81)84899-0. PMC 1327434. PMID 6261850.
- ^ Rizo, Josep (2018-07-10). "Mechanism of neurotransmitter release coming into focus". Protein Science (Review). 27 (8): 1364–1391. doi:10.1002/pro.3445. ISSN 0961-8368. PMC 6153415. PMID 29893445.
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.
- ^ Südhof TC, Rizo J (December 2011). "Synaptic vesicle exocytosis". Cold Spring Harbor Perspectives in Biology. 3 (12): a005637. doi:10.1101/cshperspect.a005637. PMC 3225952. PMID 22026965.
- ^ Zucker, Robert S.; Regehr, Wade G. (2002). "Short-Term Synaptic Plasticity". Annual Review of Physiology. 64 (1): 355–405. doi:10.1146/annurev.physiol.64.092501.114547. ISSN 0066-4278.
- ^ Burrone, Juan; Li, Zhiying; Murthy, Venkatesh N (2006). "Studying vesicle cycling in presynaptic terminals using the genetically encoded probe synaptopHluorin". Nature Protocols. 1 (6): 2970–2978. doi:10.1038/nprot.2006.449. ISSN 1754-2189.
- ^ Marvin, Jonathan S; Borghuis, Bart G; Tian, Lin; Cichon, Joseph; Harnett, Mark T; Akerboom, Jasper; Gordus, Andrew; Renninger, Sabine L; Chen, Tsai-Wen; Bargmann, Cornelia I; Orger, Michael B; Schreiter, Eric R; Demb, Jonathan B; Gan, Wen-Biao; Hires, S Andrew (2013). "An optimized fluorescent probe for visualizing glutamate neurotransmission". Nature Methods. 10 (2): 162–170. doi:10.1038/nmeth.2333. ISSN 1548-7091. PMC 4469972. PMID 23314171.
{{cite journal}}: CS1 maint: PMC format (link) - ^ Dürst, Céline D.; Wiegert, J. Simon; Schulze, Christian; Helassa, Nordine; Török, Katalin; Oertner, Thomas G. (2022-10-17). "Vesicular release probability sets the strength of individual Schaffer collateral synapses". Nature Communications. 13 (1). doi:10.1038/s41467-022-33565-6. ISSN 2041-1723. PMC 9576736. PMID 36253353.
{{cite journal}}: CS1 maint: PMC format (link) - ^ Toni N, Buchs PA, Nikonenko I, Bron CR, Muller D (November 1999). "LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite". Nature. 402 (6760): 421–5. Bibcode:1999Natur.402..421T. doi:10.1038/46574. PMID 10586883. S2CID 205056308.