Editing Axon (section)

==Anatomy==
[[File:Neuron.svg|thumb|upright=1.4|Structure of a typical neuron in the [[peripheral nervous system]]]]
[[File:Human brain right dissected lateral view description.JPG|thumb|A dissected human brain, showing [[grey matter]] and [[white matter]]]]

Axons are the primary transmission lines of the [[nervous system]], and as bundles they form [[nerve]]s in the peripheral nervous system, or [[nerve tract]]s in the [[central nervous system]] (CNS). Some axons can extend up to one meter or more while others extend as little as one millimeter. The longest axons in the human body are those of the [[sciatic nerve]], which run from the base of the [[spinal cord]] to the big toe of each foot. The diameter of axons is also variable. Most individual axons are microscopic in diameter (typically about one [[micrometre|micrometer]] (μm) across). The largest mammalian axons can reach a diameter of up to 20&nbsp;μm. The [[squid giant axon]], which is specialized to conduct signals very rapidly, is close to 1 millimeter in diameter, the size of a small pencil lead. The numbers of axonal telodendria (the branching structures at the end of the axon) can also differ from one nerve fiber to the next. Axons in the CNS typically show multiple telodendria, with many synaptic end points. In comparison, the [[cerebellar granule cell]] axon is characterized by a single T-shaped branch node from which two [[parallel fiber]]s extend. Elaborate branching allows for the simultaneous transmission of messages to a large number of target [[neuron]]s within a single region of the brain.

There are two types of axons in the nervous system: [[myelin]]ated and [[unmyelinated]] axons.<ref name="Debanne">{{cite journal | vauthors = Debanne D, Campanac E, Bialowas A, Carlier E, Alcaraz G | s2cid = 13916255 | title = Axon physiology | journal = Physiological Reviews | volume = 91 | issue = 2 | pages = 555–602 | date = April 2011 | pmid = 21527732 | doi = 10.1152/physrev.00048.2009 | url = https://hal-amu.archives-ouvertes.fr/hal-01766861/file/Debanne-Physiol-Rev-2011.pdf }}</ref> [[Myelin]] is a layer of a fatty insulating substance, which is formed by two types of [[neuroglia|glial cells]]: [[Schwann cell]]s and [[oligodendrocyte]]s. In the [[peripheral nervous system]] Schwann cells form the myelin sheath of a myelinated axon. Oligodendrocytes form the insulating myelin in the CNS. Along myelinated nerve fibers, gaps in the myelin sheath known as [[nodes of Ranvier]] occur at evenly spaced intervals. The myelination enables an especially rapid mode of electrical impulse propagation called [[saltatory conduction]].

The myelinated axons from the [[cortical neurons]] form the bulk of the neural tissue called [[white matter]] in the brain. The myelin gives the white appearance to the [[Neural tissue|tissue]] in contrast to the [[grey matter]] of the cerebral cortex which contains the neuronal cell bodies. A similar arrangement is seen in the [[cerebellum]]. Bundles of myelinated axons make up the nerve tracts in the CNS, and where they cross the midline of the brain to connect opposite regions they are called [[commissural fiber|commissures]]. The largest of these is the [[corpus callosum]] that connects the two [[cerebral hemisphere]]s, and this has around 20 million axons.<ref name="Luders" />

The structure of a neuron is seen to consist of two separate functional regions, or compartments{{Snd}}the cell body together with the dendrites as one region, and the axonal region as the other.

===Axonal region===
The axonal region or compartment, includes the axon hillock, the initial segment, the rest of the axon, and the axon telodendria, and axon terminals. It also includes the myelin sheath. The [[Nissl bodies]] that produce the neuronal proteins are absent in the axonal region.<ref name="LS" /> Proteins needed for the growth of the axon, and the removal of waste materials, need a framework for transport. This [[axonal transport]] is provided for in the axoplasm by arrangements of [[microtubule]]s and [[Intermediate filaments#Type IV|type IV intermediate filament]]s known as [[neurofilament]]s.

====Axon hillock====
[[File:Neuron Cell Body.png|thumb|right|upright=1.75|Detail showing microtubules at axon hillock and initial segment.]]
The [[axon hillock]] is the area formed from the cell body of the neuron as it extends to become the axon. It precedes the initial segment. The received [[action potential]]s that are [[summation (neurophysiology)|summed]] in the neuron are transmitted to the axon hillock for the generation of an action potential from the initial segment.

====Axonal initial segment====
The '''axonal initial segment''' (AIS) is a structurally and functionally separate microdomain of the axon.<ref name="Nelson">{{cite journal | vauthors = Nelson AD, Jenkins PM | title = Axonal Membranes and Their Domains: Assembly and Function of the Axon Initial Segment and Node of Ranvier | journal = Frontiers in Cellular Neuroscience | volume = 11 | pages = 136 | date = 2017 | pmid = 28536506 | pmc = 5422562 | doi = 10.3389/fncel.2017.00136 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Leterrier C, Clerc N, Rueda-Boroni F, Montersino A, Dargent B, Castets F | title = Ankyrin G Membrane Partners Drive the Establishment and Maintenance of the Axon Initial Segment | language = en | journal = Frontiers in Cellular Neuroscience | volume = 11 | pages = 6 | date = 2017 | pmid = 28184187 | pmc = 5266712 | doi = 10.3389/fncel.2017.00006 | doi-access = free }}</ref> One function of the initial segment is to separate the main part of an axon from the rest of the neuron; another function is to help initiate action potentials.<ref>{{cite journal | vauthors = Leterrier C | title = The Axon Initial Segment: An Updated Viewpoint | journal = The Journal of Neuroscience | volume = 38 | issue = 9 | pages = 2135–2145 | date = February 2018 | pmid = 29378864 | pmc = 6596274 | doi = 10.1523/jneurosci.1922-17.2018 }}</ref> Both of these functions support neuron [[cell polarity]], in which dendrites (and, in some cases the [[Soma (biology)|soma]]) of a neuron receive input signals at the basal region, and at the apical region the neuron's axon provides output signals.<ref>{{cite journal | vauthors = Rasband MN | title = The axon initial segment and the maintenance of neuronal polarity | language = En | journal = Nature Reviews. Neuroscience | volume = 11 | issue = 8 | pages = 552–62 | date = August 2010 | pmid = 20631711 | doi = 10.1038/nrn2852 | s2cid = 23996233 }}</ref>

The axon initial segment is unmyelinated and contains a specialized complex of proteins. It is between approximately 20 and 60&nbsp;μm in length and functions as the site of action potential initiation.<ref name="Jones">{{cite journal | vauthors = Jones SL, Svitkina TM | title = Axon Initial Segment Cytoskeleton: Architecture, Development, and Role in Neuron Polarity | journal = Neural Plasticity | volume = 2016 | pages = 6808293 | date = 2016 | pmid = 27493806 | pmc = 4967436 | doi = 10.1155/2016/6808293 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Clark BD, Goldberg EM, Rudy B | title = Electrogenic tuning of the axon initial segment | journal = The Neuroscientist | volume = 15 | issue = 6 | pages = 651–68 | date = December 2009 | pmid = 20007821 | pmc = 2951114 | doi = 10.1177/1073858409341973 }}</ref> Both the position on the axon and the length of the AIS can change showing a degree of plasticity that can fine-tune the neuronal output.<ref name="Jones"/><ref name="Yamada">{{cite journal | vauthors = Yamada R, Kuba H | title = Structural and Functional Plasticity at the Axon Initial Segment | journal = Frontiers in Cellular Neuroscience | volume = 10 | pages = 250 | date = 2016 | pmid = 27826229 | pmc = 5078684 | doi = 10.3389/fncel.2016.00250 | doi-access = free }}</ref> A longer AIS is associated with a greater excitability.<ref name="Yamada"/> Plasticity is also seen in the ability of the AIS to change its distribution and to maintain the activity of neural circuitry at a constant level.<ref name="Susuki"/>

The AIS is highly specialized for the fast conduction of [[Action potential|nerve impulses]]. This is achieved by a high concentration of [[Voltage-gated sodium channel|voltage-gated sodium channels]] in the initial segment where the action potential is initiated.<ref name="Susuki">{{cite journal | vauthors = Susuki K, Kuba H | title = Activity-dependent regulation of excitable axonal domains | journal = The Journal of Physiological Sciences | volume = 66 | issue = 2 | pages = 99–104 | date = March 2016 | pmid = 26464228 | doi = 10.1007/s12576-015-0413-4 | s2cid = 18862030 | doi-access = free | pmc = 10717305 }}</ref> The ion channels are accompanied by a high number of [[cell adhesion molecule]]s and [[scaffold protein]]s that anchor them to the cytoskeleton.<ref name="Jones"/> Interactions with [[Ankyrin-3|ankyrin-G]] are important as it is the major organizer in the AIS.<ref name="Jones"/>

In other cases as seen in rat studies an axon originates from a dendrite; such axons are said to have "dendritic origin". Some axons with dendritic origin similarly have a "proximal" initial segment that starts directly at the axon origin, while others have a "distal" initial segment, discernibly separated from the axon origin.<ref name="Höfflin-2017" /> In many species some of the neurons have axons that emanate from the dendrite and not from the cell body, and these are known as axon-carrying dendrites.<ref name=Triarhou/> In many cases, an axon originates at an axon hillock on the soma; such axons are said to have "somatic origin". Some axons with somatic origin have a "proximal" initial segment adjacent the axon hillock, while others have a "distal" initial segment, separated from the soma by an extended axon hillock.<ref name="Höfflin-2017">{{cite journal | vauthors = Höfflin F, Jack A, Riedel C, Mack-Bucher J, Roos J, Corcelli C, Schultz C, Wahle P, Engelhardt M | display-authors = 6 | title = Heterogeneity of the Axon Initial Segment in Interneurons and Pyramidal Cells of Rodent Visual Cortex | language = en | journal = Frontiers in Cellular Neuroscience | volume = 11 | pages = 332 | date = 2017 | pmid = 29170630 | pmc = 5684645 | doi = 10.3389/fncel.2017.00332 | doi-access = free }}</ref>

===Axonal transport===
{{Main|Axonal transport}}
The [[axoplasm]] is the equivalent of [[cytoplasm]] in the cell. Microtubules form in the axoplasm at the axon hillock. They are arranged along the length of the axon, in overlapping sections, and all point in the same direction{{Snd}}towards the axon terminals.<ref name="Essential">{{cite book|last1=Alberts|first1=Bruce|name-list-style=vanc|title=Essential cell biology: an introduction to the molecular biology of the cell|date=2004|publisher=Garland|location=New York|isbn=978-0-8153-3481-1|pages=[https://archive.org/details/essentialcellbio00albe/page/584 584–587]|edition=2nd|url=https://archive.org/details/essentialcellbio00albe/page/584}}</ref> This is noted by the positive endings of the microtubules. This overlapping arrangement provides the routes for the transport of different materials from the cell body.<ref name="Essential" /> Studies on the axoplasm has shown the movement of numerous vesicles of all sizes to be seen along cytoskeletal filaments{{Snd}}the microtubules, and [[neurofilament]]s, in both directions between the axon and its terminals and the cell body.

Outgoing [[Axonal transport#Anterograde transport|anterograde transport]] from the cell body along the axon, carries [[mitochondria]] and [[membrane protein]]s needed for growth to the axon terminal. Ingoing [[Axonal transport#Retrograde transport|retrograde transport]] carries cell waste materials from the axon terminal to the cell body.<ref name="MBC">{{cite book |last1=Alberts |first1=Bruce | name-list-style = vanc |title=Molecular biology of the cell |date=2002 |publisher=Garland |location=New York |isbn=978-0-8153-4072-0 |pages=979–981 |edition=4th}}</ref> Outgoing and ingoing tracks use different sets of [[motor protein]]s.<ref name="Essential" /> Outgoing transport is provided by [[kinesin]], and ingoing return traffic is provided by [[dynein]]. Dynein is minus-end directed.<ref name="MBC" /> There are many forms of kinesin and dynein motor proteins, and each is thought to carry a different cargo.<ref name="Essential" /> The studies on transport in the axon led to the naming of kinesin.<ref name="Essential" />

===Myelination===
[[File:Myelinated neuron.jpg|thumb|left|[[Transmission electron micrograph|TEM]] of a myelinated axon in cross-section.]]
[[File:Myelin sheath (1).svg|thumb|upright|Cross section of an axon: (1) Axon (2) Nucleus
(3) [[Schwann cell]] (4) [[Myelin sheath]] (5) [[Neurilemma]]]]
In the nervous system, axons may be [[myelin]]ated, or unmyelinated. This is the provision of an insulating layer, called a myelin sheath. The myelin membrane is unique in its relatively high lipid to protein ratio.<ref name="Ozgen">{{cite journal |last1=Ozgen |first1=H |last2=Baron |first2=W |last3=Hoekstra |first3=D |last4=Kahya |first4=N |title=Oligodendroglial membrane dynamics in relation to myelin biogenesis. |journal=Cellular and Molecular Life Sciences |date=September 2016 |volume=73 |issue=17 |pages=3291–310 |doi=10.1007/s00018-016-2228-8 |pmid=27141942|pmc=4967101 }}</ref>

In the peripheral nervous system axons are myelinated by [[neuroglia|glial cells]] known as [[Schwann cell]]s. In the central nervous system the myelin sheath is provided by another type of glial cell, the [[oligodendrocyte]]. Schwann cells myelinate a single axon. An oligodendrocyte can myelinate up to 50 axons.<ref name="Sadler">{{cite book|last1=Sadler|first1=T.|title=Langman's medical embryology|url=https://archive.org/details/langmansmedicale00sadl_655|url-access=limited|date=2010|publisher=Lippincott William & Wilkins|location=Philadelphia|isbn=978-0-7817-9069-7|page=[https://archive.org/details/langmansmedicale00sadl_655/page/n311 300]|edition=11th}}</ref>

The composition of myelin is different in the two types. In the CNS the major myelin protein is [[proteolipid protein]], and in the PNS it is [[myelin basic protein]].

===Nodes of Ranvier===
{{Main|Node of Ranvier}}
[[Node of Ranvier|Nodes of Ranvier]] (also known as ''myelin sheath gaps'') are short unmyelinated segments of a [[myelin|myelinated axon]], which are found periodically interspersed between segments of the myelin sheath. Therefore, at the point of the node of Ranvier, the axon is reduced in diameter.<ref>{{cite journal | vauthors = Hess A, Young JZ | title = The nodes of Ranvier | journal = Proceedings of the Royal Society of London. Series B, Biological Sciences | volume = 140 | issue = 900 | pages = 301–20 | date = November 1952 | pmid = 13003931 | doi = 10.1098/rspb.1952.0063 | series = Series B | bibcode = 1952RSPSB.140..301H | jstor = 82721 | s2cid = 11963512 }}</ref> These nodes are areas where action potentials can be generated. In [[saltatory conduction]], electrical currents produced at each node of Ranvier are conducted with little attenuation to the next node in line, where they remain strong enough to generate another action potential. Thus in a myelinated axon, action potentials effectively "jump" from node to node, bypassing the myelinated stretches in between, resulting in a propagation speed much faster than even the fastest unmyelinated axon can sustain.

===Axon terminals===
{{Main|Axon terminal}}
An axon can divide into many branches called telodendria (Greek for 'end of tree'). At the end of each '''telodendron''' is an [[axon terminal]] (also called a terminal bouton or synaptic bouton, or [[Wikt:end-foot|end-foot]]).<ref name="MW">{{cite web |title=Medical Definition of bouton |url=https://www.merriam-webster.com/medical/bouton |website=www.merriam-webster.com |access-date=21 September 2024 |language=en}}</ref> Axon terminals contain [[synaptic vesicle]]s that store the [[neurotransmitter]] for release at the [[Chemical synapse|synapse]]. This makes multiple synaptic connections with other neurons possible. Sometimes the axon of a neuron may synapse onto dendrites of the same neuron, when it is known as an [[autapse]]. Some synaptic junctions appear along the length of an axon as it extends; these are called '''en passant boutons''' ("in passing boutons") and can be in the hundreds or even the thousands along one axon.<ref name="LS">{{cite book|last1=Squire|first1=Larry|title=Fundamental neuroscience|date=2013|publisher=Elsevier/Academic Press|location=Amsterdam|isbn=978-0-12-385-870-2|pages=61–65|edition=4th}}</ref>

====Axonal varicosities====
In the normally developed brain, along the shaft of some axons are located pre-synaptic boutons also known as '''axonal varicosities''' and these have been found in regions of the [[hippocampus]] that function in the release of neurotransmitters.<ref name="Gu">{{cite journal |vauthors=Gu C |title=Rapid and Reversible Development of Axonal Varicosities: A New Form of Neural Plasticity |journal=Front Mol Neurosci |volume=14 |issue= |pages=610857 |date=2021 |pmid=33613192 |pmc=7886671 |doi=10.3389/fnmol.2021.610857 |url= |doi-access=free }}</ref> However, axonal varicosities are also present in neurodegenerative diseases where they interfere with the conduction of an action potential. Axonal varicosities are also the hallmark of [[traumatic brain injuries]].<ref name="Gu"/><ref name="Weber">{{cite journal |vauthors=Weber MT, Arena JD, Xiao R, Wolf JA, Johnson VE |title=CLARITY reveals a more protracted temporal course of axon swelling and disconnection than previously described following traumatic brain injury |journal=Brain Pathol |volume=29 |issue=3 |pages=437–450 |date=May 2019 |pmid=30444552 |pmc=6482960 |doi=10.1111/bpa.12677 |url=}}</ref> Axonal damage is usually to the axon  cytoskeleton disrupting transport. As a consequence protein accumulations such as [[amyloid-beta precursor protein]] can build up in a swelling resulting in a number of varicosities along the axon.<ref name="Gu"/><ref name="Weber"/>