Editing Synaptic vesicle (section)

== Structure ==
[[File:Hippocampal neurons.jpg|thumb|350px|Primary [[Hippocampus|hippocampal]] [[neuron]]s observed at 10 days ''in vitro'' by [[confocal microscopy]]. In both images neurons are stained with a somatodendritic marker, [[microtubule associated protein]] (red). In the right image, synaptic vesicles are stained in green (yellow where the green and red overlap). Scale bar = 25 μm.<ref>{{cite journal|last1=Tonna|first1=Noemi|last2=Bianco|first2=Fabio|last3=Matteoli|first3=Michela|last4=Cagnoli|first4=Cinzia|last5=Antonucci|first5=Flavia|last6=Manfredi|first6=Amedea|last7=Mauro|first7=Nicolò|last8=Ranucci|first8=Elisabetta|last9=Ferruti|first9=Paolo|title=A soluble biocompatible guanidine-containing polyamidoamine as promoter of primary brain cell adhesion and in vitro cell culturing|journal=Science and Technology of Advanced Materials|volume=15|issue=4|year=2014|pages=045007|doi=10.1088/1468-6996/15/4/045007|pmid=27877708|pmc=5090696|bibcode=2014STAdM..15d5007T}}</ref>]]

Synaptic vesicles are relatively simple because only a limited number of proteins fit into a sphere of 40&nbsp;nm diameter. Purified vesicles have a [[protein]]:[[phospholipid]] ratio of 1:3 with a lipid composition of 40% [[phosphatidylcholine]], 32% [[phosphatidylethanolamine]], 12% [[phosphatidylserine]], 5% [[phosphatidylinositol]], and 10% [[cholesterol]].<ref name=1synapse>{{Cite journal | last1 = Benfenati | first1 = F. | last2 = Greengard | first2 = P. | last3 = Brunner | first3 = J. | last4 = Bähler | first4 = M. | title = Electrostatic and hydrophobic interactions of synapsin I and synapsin I fragments with phospholipid bilayers | journal = The Journal of Cell Biology | volume = 108 | issue = 5 | pages = 1851–1862 | year = 1989 | pmid = 2497105 | pmc = 2115549 | doi=10.1083/jcb.108.5.1851}}</ref>

Synaptic vesicles contain two classes of obligatory components: [[transport proteins]] involved in neurotransmitter uptake, and trafficking proteins that participate in synaptic vesicle [[exocytosis]], [[endocytosis]], and recycling.
* Transport proteins are composed of [[proton pump]]s that generate [[electrochemical gradient]]s, which allow for neurotransmitter uptake, and neurotransmitter transporters that regulate the actual uptake of neurotransmitters. The necessary proton gradient is created by [[V-ATPase]], which breaks down [[adenosine triphosphate|ATP]] for energy. [[Vesicular transport protein|Vesicular transporter]]s move neurotransmitters from the cells' cytoplasm into the synaptic vesicles. Vesicular [[glutamate transporter]]s, for example, sequester glutamate into vesicles by this process.
* Trafficking proteins are more complex. They include intrinsic [[membrane protein]]s, peripherally bound proteins, and proteins such as [[SNARE (protein)|SNAREs]]. These proteins do not share a characteristic that would make them identifiable as synaptic vesicle proteins, and little is known about how these proteins are specifically deposited into synaptic vesicles. Many but not all of the known synaptic vesicle proteins interact with non-vesicular proteins and are linked to specific functions.<ref name=1synapse/>

The [[stoichiometry]] for the movement of different neurotransmitters into a vesicle is given in the following table.

{| border="1" cellpadding="3" style="border-collapse:collapse"
|- bgcolor="#cccccc"
! Neurotransmitter type(s) || Inward movement || Outward movement
|-
| [[norepinephrine]], [[dopamine]], [[histamine]], [[serotonin]] and [[acetylcholine]] || neurotransmitter<sup>+</sup> || 2 H<sup>+</sup>
|-
| [[GABA]] and [[glycine]] || neurotransmitter || 1 H<sup>+</sup>
|-
| [[glutamate]] || neurotransmitter<sup>−</sup> + Cl<sup>−</sup> || 1 H<sup>+</sup>
|}
Recently, it has been discovered that synaptic vesicles also contain small RNA molecules, including [[transfer RNA]] fragments, [[Y RNA]] fragments and [[MicroRNA|mirRNAs]].<ref>{{Cite journal|last1=Li|first1=Huinan|last2=Wu|first2=Cheng|last3=Aramayo|first3=Rodolfo|last4=Sachs|first4=Matthew S.|last5=Harlow|first5=Mark L.|date=2015-10-08|title=Synaptic vesicles contain small ribonucleic acids (sRNAs) including transfer RNA fragments (trfRNA) and microRNAs (miRNA)|journal=Scientific Reports|language=en|volume=5|issue=1 |doi=10.1038/srep14918|pmc=4597359|pmid=26446566|page=14918|bibcode=2015NatSR...514918L}}</ref> This discovery is believed to have broad impact on studying chemical synapses.

=== Effects of neurotoxins ===
Some [[neurotoxin]]s, such as [[batrachotoxin]], are known to destroy synaptic vesicles. The [[tetanus]] toxin damages [[vesicle-associated membrane protein]]s (VAMP), a type of [[v-SNARE]], while [[botulinum toxin]]s damage [[t-SNARE]]S and v-SNARES and thus inhibit synaptic transmission.<ref>{{cite book | veditors=Kandel ER, Schwartz JH, Jessell TM | title=Principles of Neural Science | chapter=Transmitter Release | edition=4th | year=2000 | publisher=McGraw-Hill | location=New York | isbn=978-0-8385-7701-1 | url-access=registration | url=https://archive.org/details/isbn_9780838577011 }}</ref> A [[Spider bite|spider toxin]] called [[alpha-Latrotoxin]] binds to [[neurexin]]s, damaging vesicles and causing massive release of neurotransmitters.{{cn|date=December 2022}}

=== Vesicle pools ===
Vesicles in the nerve terminal are grouped into three pools: the readily releasable pool, the recycling pool, and the reserve pool.<ref name="Rizzoli_Betz_2005">{{cite journal|last1=Rizzoli|first1=Silvio O|last2=Betz|first2=William J|title=Synaptic vesicle pools|journal=Nature Reviews Neuroscience|date=January 2005|volume=6|issue=1|pages=57–69|pmid=15611727|doi=10.1038/nrn1583|s2cid=7473893}}</ref> These pools are distinguished by their function and position in the nerve terminal. The readily releasable pool are docked to the [[cell membrane]], making these the first group of vesicles to be released on stimulation. The readily releasable pool is small and is quickly exhausted. The recycling pool is proximate to the cell membrane, and tend to be cycled at moderate stimulation, so that the rate of vesicle release is the same as, or lower than, the rate of vesicle formation. This pool is larger than the readily releasable pool, but it takes longer to become mobilised. The reserve pool contains vesicles that are not released under normal conditions. This reserve pool can be quite large (~50%) in neurons grown on a glass substrate, but is very small or absent at mature synapses in intact brain tissue.<ref>{{Cite journal|last1=Rose|first1=Tobias|last2=Schoenenberger|first2=Philipp|last3=Jezek|first3=Karel|last4=Oertner|first4=Thomas G.|title=Developmental Refinement of Vesicle Cycling at Schaffer Collateral Synapses|journal=Neuron|volume=77|issue=6|pages=1109–1121|doi=10.1016/j.neuron.2013.01.021|pmid=23522046|year=2013|doi-access=free}}</ref><ref>{{Cite journal|last1=Xue|first1=Lei|last2=Sheng|first2=Jiansong|last3=Wu|first3=Xin-Sheng|last4=Wu|first4=Wei|last5=Luo|first5=Fujun|last6=Shin|first6=Wonchul|last7=Chiang|first7=Hsueh-Cheng|last8=Wu|first8=Ling-Gang|date=2013-05-15|title=Most Vesicles in a Central Nerve Terminal Participate in Recycling|journal=Journal of Neuroscience|volume=33|issue=20|pages=8820–8826|doi=10.1523/jneurosci.4029-12.2013|pmid=23678124|pmc=3710729}}</ref>