Editing Synaptic vesicle (section)

== History ==
With the advent of the [[electron microscope]] in the early 1950s, nerve endings were found to contain a large number of electron-lucent (transparent to electrons) vesicles.<ref>
{{cite journal
<!-- From the PDF: Electron microscope study of the cytoplasm of neurons. Sanford L. PALAY,' The Rockefeller Institute for Medical Research. (Assisted by George E. Palade) 'Permanent address: Department of Anatomy, Yale University School of Nedicine. --> |last1=Palay |first1=Sanford L. |last2=Palade |first2=George E. |title=Electron microscope study of the cytoplasm of neurons |journal= The Anatomical Record |year=1954 |volume=118 |doi=10.1002/ar.1091180211 |type=Oral presentation |page=336}}</ref><ref>{{cite journal |last1=Eduardo D. P. |first1=De Robertis |first2=Bennett, H. |last2=Stanley |title=Some Features of the Submicroscopic Morphology of Synapses in Frog and Earthworm |journal=The Journal of Biophysical and Biochemical Cytology |date=January 25, 1955 |volume=1 |issue=1 |pages=47–58 |pmc=2223594 |pmid=14381427 |jstor=1602913|doi=10.1083/jcb.1.1.47 }}</ref> The term synaptic vesicle was first introduced by De Robertis and Bennett in 1954.<ref>{{cite journal|vauthors=((De Robertis EDP)), Bennett HS |year=1954|title= Submicroscopic vesicular component in the synapse|journal= Fed Proc |volume=13|pages=35}}</ref> This was shortly after transmitter release at the frog [[neuromuscular junction]] was found to induce postsynaptic [[miniature end-plate potential]]s that were ascribed to the release of discrete packages of [[neurotransmitter]] (quanta) from the presynaptic nerve terminal.<ref>{{cite journal |last=Fatt |first=P. |author2=Katz, B. |title=Some Observations on Biological Noise |journal=Nature |date=7 October 1950 |volume=166 |issue=4223 |pages=597–598 |doi=10.1038/166597a0 |pmid=14780165 |bibcode=1950Natur.166..597F|s2cid=9117892 }}</ref><ref>{{cite journal |last=Fatt |first=P. |author2=Katz, B. |title=Spontaneous subthreshold activity at motor nerve endings |journal=The Journal of Physiology |date=May 28, 1952 |volume=117 |issue=1 |pages=109–128 |pmid=14946732 |url=http://204.71.142.23/skins/main/pdf/HistoryofNeuroscience/fatt2.pdf |access-date=1 February 2014 |doi=10.1113/jphysiol.1952.sp004735 |pmc=1392564 |archive-date=2 February 2014 |archive-url=https://web.archive.org/web/20140202120031/http://204.71.142.23/skins/main/pdf/HistoryofNeuroscience/fatt2.pdf |url-status=dead }}</ref> It was thus reasonable to hypothesize that the transmitter substance ([[acetylcholine]]) was contained in such vesicles, which by a secretory mechanism would release their contents into the [[chemical synapse|synaptic cleft]] (vesicle hypothesis).<ref>{{cite journal|pmc=1366292|pmid=13175199|vauthors=Del Castillo JB, Katz B |year=1954|title= Quantal components of the endplate potential|journal= J. Physiol.|volume=124|issue=3|pages= 560–573|doi=10.1113/jphysiol.1954.sp005129}}</ref><ref>{{cite journal|vauthors=Del Castillo JB, Katz B |year=1954|title= Biophysical aspects of neuromuscular transmission|journal= Prog Biophys Biophys Chem |volume=6|pages= 121–170|pmid=13420190}}</ref>

The missing link was the demonstration that the neurotransmitter [[acetylcholine]] is actually contained in synaptic vesicles. About ten years later, the application of [[cell fractionation|subcellular fractionation]] techniques to brain tissue permitted the isolation first of nerve endings ([[synaptosome]]s),<ref>{{cite journal|vauthors=Gray EG, Whittaker VP |year=1962|title= The isolation of nerve endings from brain: an electron microscopic study of cell fragments derived from homogenization and centrifugation|pmid=13901297|pmc=1244174|journal= J Anat |volume=96|issue=Pt 1 |pages= 79–88}}</ref> and subsequently of synaptic vesicles from mammalian brain. Two competing laboratories were involved in this work, that of [[Victor P. Whittaker]] at the Institute of Animal Physiology, Agricultural Research Council, Babraham, Cambridge, UK and that of [[Eduardo de Robertis]] at the Instituto de Anatomía General y Embriología, Facultad de Medicina, Universidad de Buenos Aires, Argentina.<ref>{{cite book |last1=Zimmermann |first1=Herbert |title=The discovery of the synaptosome and its implications. |chapter=Victor P. Whittaker: The Discovery of the Synaptosome and Its Implications |journal=Neuromethods |date=2018 |volume=141 |pages=9–26 |location=New York, NY |doi=10.1007/978-1-4939-8739-9_2|isbn=978-1-4939-8738-2 }}</ref> Whittaker's work demonstrating acetylcholine in vesicle fractions from [[guinea-pig]] brain was first published in abstract form in 1960 and then in more detail in 1963 and 1964,<ref>{{cite journal|vauthors=Whittaker VP, Michaelson IA, Kirkland RJ |year=1963|title= The separation of synaptic vesicles from disrupted nerve ending particles|pmid=14000416|journal= Biochem Pharmacol |volume=12|issue=2|pages=300–302|doi=10.1016/0006-2952(63)90156-4}}</ref><ref>{{cite journal|vauthors=Whittaker VP, Michaelson IA, Kirkland RJ |year=1964|title= The separation of synaptic vesicles from nerve ending particles ('synaptosomes')|pmc=1202615|pmid=5834239|journal=Biochem J|volume= 90|issue=2|pages= 293–303|doi=10.1042/bj0900293 }}</ref> and the paper of the de Robertis group demonstrating an enrichment of bound acetylcholine in synaptic vesicle fractions from rat brain appeared in 1963.<ref>{{cite journal|vauthors=De Robertis E, Rodriguez de Lores Arnaiz G, Salganicoff GL, Pellegrino de Iraldi A, Zieher LM |year=1963|title= Isolation of synaptic vesicles and structural organization of the acetylcholine system within brain nerve endings|doi=10.1111/j.1471-4159.1963.tb05038.x|pmid=14026026|journal= J Neurochem |volume=10|issue=4|pages=225–235|s2cid=33266876}}</ref> Both groups released synaptic vesicles from isolated synaptosomes by [[osmotic shock]]. The content of acetylcholine in a vesicle was originally estimated to be 1000–2000 molecules.<ref>{{cite journal|vauthors=Whittaker VP, Sheridan MN |year=1965|title= The morphology and acetylcholine content of isolated cerebral cortical synaptic vesicles|pmid=14333293|doi=10.1111/j.1471-4159.1965.tb04237.x|journal= J Neurochem |volume=12|issue=5|pages= 363–372|s2cid=5746357}}</ref> Subsequent work identified the vesicular localization of other neurotransmitters, such as [[amino acid]]s, [[catecholamine]]s, [[serotonin]], and [[Adenosine triphosphate|ATP]]. Later, synaptic vesicles could also be isolated from other tissues such as the [[superior cervical ganglion]],<ref>{{cite journal|vauthors=Wilson WS, Schulz RA, Cooper JR |year=1973|title= The isolation of cholinergic synaptic vesicles from bovine superior cervical ganglion and estimation of their acetylcholine content|pmid=4574192|doi=10.1111/j.1471-4159.1973.tb00026.x|journal= J Neurochem |volume=20|issue=3|pages= 659–667|s2cid=6157415}}</ref> or the [[octopus]] brain.<ref>{{cite journal|author=Jones DG |year=1970|title= The isolation of synaptic vesicles from Octopus brain|pmid=5412681|doi=10.1016/0006-8993(70)90077-6|journal=Brain Res|volume= 17|issue=2|pages=181–193}}</ref> The isolation of highly purified fractions of cholinergic synaptic vesicles from the ray [[Torpedo (genus)|''Torpedo'']] [[Electric organ (biology)|electric organ]]<ref>{{cite journal|vauthors=Israël M, Gautron J, Lesbats B |year=1970|title= Subcellular fractionation of the electric organ of ''Torpedo marmorata'' |pmid=5471906|journal=J Neurochem|volume=17|issue=10 |pages=1441–1450|doi=10.1111/j.1471-4159.1970.tb00511.x|s2cid=8087195}}</ref><ref>{{cite journal|vauthors=Whittaker VP, Essman WB, Dowe GH |year=1972|title= The isolation of pure cholinergic synaptic vesicles from the electric organs of elasmobranch fish of the family Torpidinidae|journal= Biochem J|volume= 128|issue=4|pages=833–846|doi=10.1042/bj1280833|pmid=4638794|pmc=1173903}}</ref> was an important step forward in the study of vesicle biochemistry and function.