Editing Axon

{{Short description|Long projection on a neuron that conducts signals to other neurons}}
{{Other uses}}
{{Use dmy dates|date=September 2020}}
{{Infobox anatomy
| name = Axon
| image = Blausen 0657 MultipolarNeuron.png
| caption = An axon of a multipolar neuron
| function =
| neurotransmitter =
| morphology =
| afferents =
| efferents =
}}

An '''axon''' (from Greek ἄξων ''áxōn'', axis) or '''nerve fiber''' (or '''nerve''' '''fibre''': see [[American and British English spelling differences#-re, -er|spelling differences]]) is a long, slender [[cellular extensions|projection]] of a nerve cell, or [[neuron]], in [[Vertebrate|vertebrates]], that typically conducts electrical impulses known as [[action potential]]s away from the [[Soma (biology)|nerve cell body]]. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain [[sensory neuron]]s ([[pseudounipolar neuron]]s), such as those for touch and warmth, the axons are called [[afferent nerve fiber]]s and the electrical impulse travels along these from the [[peripheral nervous system|periphery]] to the cell body and from the cell body to the spinal cord along another branch of the same axon. Axon dysfunction can be the cause of many inherited and acquired [[neurological disorder]]s that affect both the [[Peripheral nervous system|peripheral]] and [[Central nervous system|central neurons]]. Nerve fibers are [[Axon#Classification|classed]] into three types{{Snd}}[[group A nerve fiber]]s, [[group B nerve fiber]]s, and [[group C nerve fiber]]s. Groups A and B are [[myelin]]ated, and group C are unmyelinated. These groups include both sensory fibers and motor fibers. Another classification groups only the sensory fibers as Type I, Type II, Type III, and Type IV.

An axon is one of two types of [[Cellular extensions|cytoplasmic protrusions]] from the cell body of a neuron; the other type is a [[dendrite]]. Axons are distinguished from dendrites by several features, including shape (dendrites often taper while axons usually maintain a constant radius), length (dendrites are restricted to a small region around the cell body while axons can be much longer), and function (dendrites receive signals whereas axons transmit them). Some types of neurons have no axon and transmit signals from their dendrites. In some species, axons can emanate from dendrites known as axon-carrying dendrites.<ref name="Triarhou">{{cite journal | vauthors = Triarhou LC | title = Axons emanating from dendrites: phylogenetic repercussions with Cajalian hues | journal = Frontiers in Neuroanatomy | volume = 8 | pages = 133 | date = 2014 | pmid = 25477788 | pmc = 4235383 | doi = 10.3389/fnana.2014.00133 | doi-access = free }}</ref> No neuron ever has more than one axon; however in invertebrates such as insects or leeches the axon sometimes consists of several regions that function more or less independently of each other.<ref>{{cite journal | vauthors = Yau KW | title = Receptive fields, geometry and conduction block of sensory neurones in the central nervous system of the leech | journal = The Journal of Physiology | volume = 263 | issue = 3 | pages = 513–38 | date = December 1976 | pmid = 1018277 | pmc = 1307715 | doi = 10.1113/jphysiol.1976.sp011643 }}</ref>

Axons are covered by a membrane known as an [[axolemma]]; the cytoplasm within an axon is called [[axoplasm]]. Most axons branch, in some cases very profusely. The end branches of an axon are called [[telodendria]]. The swollen end of a telodendron is known as the [[axon terminal]] or end-foot which joins the dendrite or cell body of another neuron forming a [[Synapse|synaptic]] connection. Axons usually  make contact with other neurons at junctions called [[synapse]]s but can also make contact with muscle or gland cells. In some circumstances, the axon of one neuron may form a synapse with the dendrites of the same neuron, resulting in an [[autapse]]. At a synapse, the [[Cell membrane|membrane]] of the axon closely adjoins the membrane of the target cell, and special molecular structures serve to transmit electrical or electrochemical signals across the gap. 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> Other synapses appear as terminals at the ends of axonal branches.

A single axon, with all its branches taken together, can target multiple parts of the brain and generate thousands of synaptic terminals. A bundle of axons make a [[nerve tract]] in the [[central nervous system]],<ref name="Luders">{{cite journal | vauthors = Luders E, Thompson PM, Toga AW | title = The development of the corpus callosum in the healthy human brain | journal = The Journal of Neuroscience | volume = 30 | issue = 33 | pages = 10985–90 | date = August 2010 | pmid = 20720105 | pmc = 3197828 | doi = 10.1523/JNEUROSCI.5122-09.2010 }}</ref> and a [[nerve fascicle|fascicle]] in the [[peripheral nervous system]]. In [[Placentalia|placental mammals]] the largest [[white matter]] tract in the brain is the [[corpus callosum]], formed of some 200 million axons in the [[human brain]].<ref name="Luders" />

==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"/>

==Action potentials==
{{Main|Action potential}}
{{Further |Neural coding|Active zone}}
[[File:Chemical_synapse_schema_cropped.jpg|thumb|upright=1.2|[[Synapse|Synaptic connections from an axon]]]]
[[Image:SynapseSchematic en.svg|thumb|260px|Neurotransmitter released from presynaptic axon terminal, and transported across synaptic cleft to receptors on postsynaptic neuron|alt=The pre- and post-synaptic axons are separated by a short distance known as the synaptic cleft. Neurotransmitter released by pre-synaptic axons diffuse through the synaptic cleft to bind to and open ion channels in post-synaptic axons.]]

Most axons carry signals in the form of action potentials, which are discrete electrochemical impulses that travel rapidly along an axon, starting at the cell body and terminating at points where the axon makes synaptic contact with target cells. The defining characteristic of an action potential is that it is "all-or-nothing"{{Snd}}every action potential that an axon generates has essentially the same size and shape. This [[All-or-none law|all-or-nothing]] characteristic allows action potentials to be transmitted from one end of a long axon to the other without any reduction in size. There are, however, some types of neurons with short axons that carry graded electrochemical signals, of variable amplitude.

When an action potential reaches a presynaptic terminal, it activates the synaptic transmission process. The first step is rapid opening of calcium ion channels in the membrane of the axon, allowing calcium ions to flow inward across the membrane. The resulting increase in intracellular calcium concentration causes [[synaptic vesicle]]s (tiny containers enclosed by a lipid membrane) filled with a neurotransmitter chemical to fuse with the axon's membrane and empty their contents into the extracellular space. The neurotransmitter is released from the presynaptic nerve through [[exocytosis]]. The neurotransmitter chemical then diffuses across to receptors located on the membrane of the target cell. The neurotransmitter binds to these receptors and activates them. Depending on the type of receptors that are activated, the effect on the target cell can be to excite the target cell, inhibit it, or alter its metabolism in some way. This entire sequence of events often takes place in less than a thousandth of a second. Afterward, inside the presynaptic terminal, a new set of vesicles is moved into position next to the membrane, ready to be released when the next action potential arrives. The action potential is the final electrical step in the integration of synaptic messages at the scale of the neuron.<ref name="Debanne"/>

Extracellular recordings of action potential propagation in axons has been demonstrated in freely moving animals. While extracellular somatic action potentials have been used to study cellular activity in freely moving animals such as [[place cells]], axonal activity in both [[White matter|white]] and [[gray matter]] can also be recorded. Extracellular recordings of axon action potential propagation is distinct from somatic action potentials in three ways: 1. The signal has a shorter peak-trough duration (~150μs) than of [[pyramidal cell]]s (~500μs) or [[interneuron]]s (~250μs). 2. The voltage change is triphasic. 3. Activity recorded on a tetrode is seen on only one of the four recording wires. In recordings from freely moving rats, axonal signals have been isolated in white matter tracts including the alveus and the corpus callosum as well hippocampal gray matter.<ref>{{cite journal | vauthors = Robbins AA, Fox SE, Holmes GL, Scott RC, Barry JM | title = Short duration waveforms recorded extracellularly from freely moving rats are representative of axonal activity | journal = Frontiers in Neural Circuits | volume = 7 | issue = 181 | pages = 181 | date = Nov 2013 | pmid = 24348338 | pmc = 3831546 | doi = 10.3389/fncir.2013.00181 | doi-access = free }}</ref>

In fact, the generation of action potentials in vivo is sequential in nature, and these sequential spikes constitute the [[neural coding|digital codes]] in the neurons. Although previous studies indicate an axonal origin of a single spike evoked by short-term pulses, physiological signals in vivo trigger the initiation of sequential spikes at the cell bodies of the neurons.<ref>Rongjing Ge, Hao Qian and Jin-Hui Wang* (2011) Molecular Brain 4(19), 1~11</ref><ref>Rongjing Ge, Hao Qian, Na Chen and Jin-Hui Wang* (2014) Molecular Brain 7(26):1-16</ref>

In addition to propagating action potentials to axonal terminals, the axon is able to amplify the action potentials, which makes sure a secure propagation of sequential action potentials toward the axonal terminal. In terms of molecular mechanisms, [[voltage-gated sodium channel]]s in the axons possess lower [[Threshold potential|threshold]] and shorter [[Refractory period (physiology)|refractory period]] in response to short-term pulses.<ref>{{cite journal | vauthors = Chen N, Yu J, Qian H, Ge R, Wang JH | title = Axons amplify somatic incomplete spikes into uniform amplitudes in mouse cortical pyramidal neurons | journal = PLOS ONE | volume = 5 | issue = 7 | pages = e11868 | date = July 2010 | pmid = 20686619 | pmc = 2912328 | doi = 10.1371/journal.pone.0011868 | bibcode = 2010PLoSO...511868C | doi-access = free }}</ref>

==Development and growth==
===Development===
The development of the axon to its target, is one of the six major stages in the overall [[development of the nervous system]].<ref name="Wolpert">{{cite book|last1=Wolpert|first1=Lewis|title=Principles of development|date=2015|isbn=978-0-19-967814-3|pages=520–524|publisher=Oxford University Press |edition=5th}}</ref> Studies done on cultured [[hippocampus|hippocampal]] neurons suggest that neurons initially produce multiple [[neurite]]s that are equivalent, yet only one of these neurites is destined to become the axon.<ref>{{cite journal | vauthors = Fletcher TL, Banker GA | title = The establishment of polarity by hippocampal neurons: the relationship between the stage of a cell's development in situ and its subsequent development in culture | journal = Developmental Biology | volume = 136 | issue = 2 | pages = 446–54 | date = December 1989 | pmid = 2583372 | doi = 10.1016/0012-1606(89)90269-8 }}</ref> It is unclear whether axon specification precedes axon elongation or vice versa,<ref>{{cite journal | vauthors = Jiang H, Rao Y | title = Axon formation: fate versus growth | journal = Nature Neuroscience | volume = 8 | issue = 5 | pages = 544–6 | date = May 2005 | pmid = 15856056 | doi = 10.1038/nn0505-544 | s2cid = 27728967 }}</ref> although recent evidence points to the latter. If an axon that is not fully developed is cut, the polarity can change and other neurites can potentially become the axon. This alteration of polarity only occurs when the axon is cut at least 10 μm shorter than the other neurites. After the incision is made, the longest neurite will become the future axon and all the other neurites, including the original axon, will turn into dendrites.<ref>{{cite journal | vauthors = Goslin K, Banker G | title = Experimental observations on the development of polarity by hippocampal neurons in culture | journal = The Journal of Cell Biology | volume = 108 | issue = 4 | pages = 1507–16 | date = April 1989 | pmid = 2925793 | pmc = 2115496 | doi = 10.1083/jcb.108.4.1507 }}</ref> Imposing an external force on a neurite, causing it to elongate, will make it become an axon.<ref>{{cite journal | vauthors = Lamoureux P, Ruthel G, Buxbaum RE, Heidemann SR | title = Mechanical tension can specify axonal fate in hippocampal neurons | journal = The Journal of Cell Biology | volume = 159 | issue = 3 | pages = 499–508 | date = November 2002 | pmid = 12417580 | pmc = 2173080 | doi = 10.1083/jcb.200207174 }}</ref> Nonetheless, axonal development is achieved through a complex interplay between extracellular signaling, intracellular signaling and [[cytoskeleton|cytoskeletal]] dynamics.

====Extracellular signaling====
The extracellular signals that propagate through the [[extracellular matrix]] surrounding neurons play a prominent role in axonal development.<ref name="pmid17311006">{{cite journal | vauthors = Arimura N, Kaibuchi K | title = Neuronal polarity: from extracellular signals to intracellular mechanisms | journal = Nature Reviews. Neuroscience | volume = 8 | issue = 3 | pages = 194–205 | date = March 2007 | pmid = 17311006 | doi = 10.1038/nrn2056 | s2cid = 15556921 }}</ref> These signaling molecules include proteins, [[neurotrophic factors]], and extracellular matrix and adhesion molecules.
[[Netrin]] (also known as UNC-6) a secreted protein, functions in axon formation. When the [[UNC-5]] netrin receptor is mutated, several neurites are irregularly projected out of neurons and finally a single axon is extended anteriorly.<ref name="A">[[Neuroglia]] and [[pioneer neuron]]s express UNC-6 to provide global and local netrin cues for guiding migrations in [[Caenorhabditis elegans|''C. elegans'']]</ref><ref>{{cite journal | vauthors = Serafini T, Kennedy TE, Galko MJ, Mirzayan C, Jessell TM, Tessier-Lavigne M | title = The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6 | journal = Cell | volume = 78 | issue = 3 | pages = 409–24 | date = August 1994 | pmid = 8062384 | doi = 10.1016/0092-8674(94)90420-0 | s2cid = 22666205 }}</ref><ref>{{cite journal | vauthors = Hong K, Hinck L, Nishiyama M, Poo MM, Tessier-Lavigne M, Stein E | title = A ligand-gated association between cytoplasmic domains of UNC5 and DCC family receptors converts netrin-induced growth cone attraction to repulsion | journal = Cell | volume = 97 | issue = 7 | pages = 927–41 | date = June 1999 | pmid = 10399920 | doi = 10.1016/S0092-8674(00)80804-1 | s2cid = 18043414 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hedgecock EM, Culotti JG, Hall DH | title = The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans | journal = Neuron | volume = 4 | issue = 1 | pages = 61–85 | date = January 1990 | pmid = 2310575 | doi = 10.1016/0896-6273(90)90444-K | s2cid = 23974242 }}</ref> The neurotrophic factors{{Snd}}[[nerve growth factor]] (NGF), [[brain-derived neurotrophic factor]] (BDNF) and [[neurotrophin-3]] (NTF3) are also involved in axon development and bind to [[Trk receptor]]s.<ref>{{cite journal | vauthors = Huang EJ, Reichardt LF | s2cid = 10217268 | title = Trk receptors: roles in neuronal signal transduction | journal = Annual Review of Biochemistry | volume = 72 | pages = 609–42 | year = 2003 | pmid = 12676795 | doi = 10.1146/annurev.biochem.72.121801.161629 }}</ref>

The [[ganglioside]]-converting enzyme plasma membrane ganglioside [[sialidase]] (PMGS), which is involved in the activation of [[TrkA]] at the tip of neutrites, is required for the elongation of axons. PMGS asymmetrically distributes to the tip of the neurite that is destined to become the future axon.<ref name="pmid15834419">{{cite journal | vauthors = Da Silva JS, Hasegawa T, Miyagi T, Dotti CG, Abad-Rodriguez J | title = Asymmetric membrane ganglioside sialidase activity specifies axonal fate | journal = Nature Neuroscience | volume = 8 | issue = 5 | pages = 606–15 | date = May 2005 | pmid = 15834419 | doi = 10.1038/nn1442 | s2cid = 25227765 }}</ref>

====Intracellular signaling====
During axonal development, the activity of [[PI3K]] is increased at the tip of destined axon. Disrupting the activity of PI3K inhibits axonal development. Activation of PI3K results in the production of [[phosphatidylinositol (3,4,5)-trisphosphate]] (PtdIns) which can cause significant elongation of a neurite, converting it into an axon. As such, the overexpression of [[phosphatase]]s that dephosphorylate PtdIns leads into the failure of polarization.<ref name="pmid17311006" />

====Cytoskeletal dynamics====
The neurite with the lowest [[actin]] filament content will become the axon. PGMS concentration and [[Actin#F-Actin|f-actin]] content are inversely correlated; when PGMS becomes enriched at the tip of a neurite, its f-actin content is substantially decreased.<ref name="pmid15834419" /> In addition, exposure to actin-depolimerizing drugs and toxin B (which inactivates [[Rho family of GTPases|Rho-signaling]]) causes the formation of multiple axons. Consequently, the interruption of the actin network in a growth cone will promote its neurite to become the axon.<ref>{{cite journal | vauthors = Bradke F, Dotti CG | title = The role of local actin instability in axon formation | journal = Science | volume = 283 | issue = 5409 | pages = 1931–4 | date = March 1999 | pmid = 10082468 | doi = 10.1126/science.283.5409.1931 | bibcode = 1999Sci...283.1931B }}</ref>

===Growth===
{{Main|Axon guidance}}
[[File:Axon two photon.jpg|thumb|right|upright|Axon of nine-day-old mouse with growth cone visible]]
Growing axons move through their environment via the [[growth cone]], which is at the tip of the axon. The growth cone has a broad sheet-like extension called a [[lamellipodium]] which contain protrusions called [[filopodia]]. The filopodia are the mechanism by which the entire process adheres to surfaces and explores the surrounding environment. Actin plays a major role in the mobility of this system. Environments with high levels of [[cell adhesion molecule]]s (CAMs) create an ideal environment for axonal growth. This seems to provide a "sticky" surface for axons to grow along. Examples of CAMs specific to neural systems include [[Neural cell adhesion molecule|N-CAM]], [[Contactin 2|TAG-1]]{{Snd}}an axonal [[glycoprotein]]<ref name="Furley">{{cite journal | vauthors = Furley AJ, Morton SB, Manalo D, Karagogeos D, Dodd J, Jessell TM | title = The axonal glycoprotein TAG-1 is an immunoglobulin superfamily member with neurite outgrowth-promoting activity | journal = Cell | volume = 61 | issue = 1 | pages = 157–70 | date = April 1990 | pmid = 2317872 | doi = 10.1016/0092-8674(90)90223-2 | s2cid = 28813676 | doi-access = free }}</ref>{{Snd}}and [[Myelin-associated glycoprotein|MAG]], all of which are part of the [[immunoglobulin]] superfamily. Another set of molecules called [[extracellular matrix]]-[[cell adhesion molecule|adhesion molecule]]s also provide a sticky substrate for axons to grow along. Examples of these molecules include [[laminin]], [[fibronectin]], [[tenascin]], and [[perlecan]]. Some of these are surface bound to cells and thus act as short range attractants or repellents. Others are difusible ligands and thus can have long range effects.

Cells called [[guidepost cells]] assist in the [[axon guidance|guidance]] of neuronal axon growth. These cells that help [[axon guidance]], are typically other neurons that are sometimes immature. When the axon has completed its growth at its connection to the target, the diameter of the axon can increase by up to five times, depending on the [[Nerve conduction velocity|speed of conduction]] required.<ref name="Alberts">{{cite book |last1=Alberts |first1=Bruce |title=Molecular biology of the cell |date=2015 |isbn=9780815344643 |page=947 |edition=Sixth}}</ref>

It has also been discovered through research that if the axons of a neuron were damaged, as long as the soma (the cell body of a neuron) is not damaged, the axons would regenerate and remake the synaptic connections with neurons with the help of [[guidepost cells]]. This is also referred to as [[neuroregeneration]].<ref>{{cite journal | vauthors = Kunik D, Dion C, Ozaki T, Levin LA, Costantino S | title = Laser-based single-axon transection for high-content axon injury and regeneration studies | journal = PLOS ONE | volume = 6 | issue = 11 | pages = e26832 | year = 2011 | pmid = 22073205 | pmc = 3206876 | doi = 10.1371/journal.pone.0026832 | bibcode = 2011PLoSO...626832K | doi-access = free }}</ref>

[[Reticulon 4|Nogo-A]] is a type of neurite outgrowth inhibitory component that is present in the central nervous system myelin membranes (found in an axon). It has a crucial role in restricting axonal regeneration in adult mammalian central nervous system. In recent studies, if Nogo-A is blocked and neutralized, it is possible to induce long-distance axonal regeneration which leads to enhancement of functional recovery in rats and mouse spinal cord. This has yet to be done on humans.<ref>{{cite journal | vauthors = Schwab ME | title = Nogo and axon regeneration | journal = Current Opinion in Neurobiology | volume = 14 | issue = 1 | pages = 118–24 | date = February 2004 | pmid = 15018947 | doi = 10.1016/j.conb.2004.01.004 | s2cid = 9672315 }}</ref> A recent study has also found that [[macrophage]]s activated through a specific inflammatory pathway activated by the [[CLEC7A|Dectin-1]] receptor are capable of promoting axon recovery, also however causing [[neurotoxicity]] in the neuron.<ref>{{cite journal | vauthors = Gensel JC, Nakamura S, Guan Z, van Rooijen N, Ankeny DP, Popovich PG | title = Macrophages promote axon regeneration with concurrent neurotoxicity | journal = The Journal of Neuroscience | volume = 29 | issue = 12 | pages = 3956–68 | date = March 2009 | pmid = 19321792 | pmc = 2693768 | doi = 10.1523/JNEUROSCI.3992-08.2009 }}</ref>

===Length regulation===
Axons vary largely in length from a few micrometers up to meters in some animals. This emphasizes that there must be a cellular length regulation mechanism allowing the neurons both to sense the length of their axons and to control their growth accordingly. It was discovered that [[motor proteins]] play an important role in regulating the length of axons.<ref>{{cite journal | vauthors = Myers KA, Baas PW | title = Kinesin-5 regulates the growth of the axon by acting as a brake on its microtubule array | journal = The Journal of Cell Biology | volume = 178 | issue = 6 | pages = 1081–91 | date = September 2007 | pmid = 17846176 | pmc = 2064629 | doi = 10.1083/jcb.200702074 }}</ref> Based on this observation, researchers developed an explicit model for axonal growth describing how motor proteins could affect the axon length on the molecular level.<ref>{{cite journal | vauthors = Rishal I, Kam N, Perry RB, Shinder V, Fisher EM, Schiavo G, Fainzilber M | title = A motor-driven mechanism for cell-length sensing | journal = Cell Reports | volume = 1 | issue = 6 | pages = 608–16 | date = June 2012 | pmid = 22773964 | pmc = 3389498 | doi = 10.1016/j.celrep.2012.05.013 }}</ref><ref>{{cite journal | vauthors = Karamched BR, Bressloff PC | title = Delayed feedback model of axonal length sensing | journal = Biophysical Journal | volume = 108 | issue = 9 | pages = 2408–19 | date = May 2015 | pmid = 25954897 | pmc = 4423051 | doi = 10.1016/j.bpj.2015.03.055 | bibcode = 2015BpJ...108.2408K }}</ref><ref>{{cite journal | vauthors = Bressloff PC, Karamched BR | title = A frequency-dependent decoding mechanism for axonal length sensing | journal = Frontiers in Cellular Neuroscience | volume = 9 | pages = 281 | year = 2015 | pmid = 26257607 | pmc = 4508512 | doi = 10.3389/fncel.2015.00281 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Folz F, Wettmann L, [[Giovanna Morigi|Morigi G]], Kruse K | title = Sound of an axon's growth | journal = Physical Review E | volume = 99 | issue = 5–1 | pages = 050401 | date = May 2019 | pmid = 31212501 | doi = 10.1103/PhysRevE.99.050401 | arxiv = 1807.04799 | bibcode = 2019PhRvE..99e0401F | s2cid = 118682719 }}</ref> These studies suggest that motor proteins carry signaling molecules from the soma to the growth cone and vice versa whose concentration oscillates in time with a length-dependent frequency.

==Classification==
{{Further |Nerve conduction velocity}}
The axons of neurons in the human [[peripheral nervous system]] can be classified based on their physical features and signal conduction properties. Axons were known to have different thicknesses (from 0.1 to 20&nbsp;μm)<ref name="LS"/> and these differences were thought to relate to the speed at which an action potential could travel along the axon{{Snd}}its ''conductance velocity''. [[Joseph Erlanger|Erlanger]] and [[Herbert Spencer Gasser|Gasser]] proved this hypothesis, and identified several types of nerve fiber, establishing a relationship between the diameter of an axon and its nerve conduction velocity. They published their findings in 1941 giving the first classification of axons.

Axons are classified in two systems. The first one introduced by Erlanger and Gasser, grouped the fibers into three main groups using the letters A, B, and C. These groups, [[group A nerve fiber|group A]], [[group B nerve fibres|group B]], and [[group C nerve fiber|group C]] include both the sensory fibers ([[afferent nerve fiber|afferents]]) and the motor fibers ([[efferent nerve fiber|efferents]]). The first group A, was subdivided into alpha, beta, gamma, and delta fibers{{Snd}}Aα, Aβ, Aγ, and Aδ. The [[motor neuron]]s of the different motor fibers, were the [[lower motor neuron]]s{{Snd}}[[alpha motor neuron]], [[beta motor neuron]], and [[gamma motor neuron]] having the Aα, Aβ, and Aγ nerve fibers, respectively.

Later findings by other researchers identified two groups of Aa fibers that were sensory fibers. These were then introduced into a system (Lloyd classification) that only included sensory fibers (though some of these were mixed nerves and were also motor fibers). This system refers to the sensory groups as Types and uses Roman numerals: Type Ia, Type Ib, Type II, Type III, and Type IV.

=== Motor === <!-- Motor fiber types redirects here -->
Lower motor neurons have two kind of fibers:

{| class="wikitable"
|+Motor fiber types
|-
! Type !! Erlanger-Gasser<br />Classification || Diameter<br />(μm) || Myelin || Conduction velocity<br />(meters/second) !! Associated [[muscle fiber]]s
|-
! [[Alpha motor neuron|Alpha (α) motor neuron]]
| Aα || 13–20 || Yes || 80–120 ||[[Extrafusal muscle fibers]]
|-
! [[Beta motor neuron|Beta (β) motor neuron]]
| Aβ || || || ||
|-
! [[Gamma motor neuron|Gamma (γ) motor neuron]]
| Aγ || 5-8 || Yes || 4–24<ref>{{cite journal | vauthors = Andrew BL, Part NJ | title = Properties of fast and slow motor units in hind limb and tail muscles of the rat | journal = Quarterly Journal of Experimental Physiology and Cognate Medical Sciences | volume = 57 | issue = 2 | pages = 213–25 | date = April 1972 | pmid = 4482075 | doi = 10.1113/expphysiol.1972.sp002151 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Russell NJ | title = Axonal conduction velocity changes following muscle tenotomy or deafferentation during development in the rat | journal = The Journal of Physiology | volume = 298 | pages = 347–60 | date = January 1980 | pmid = 7359413 | pmc = 1279120 | doi = 10.1113/jphysiol.1980.sp013085 }}</ref> || [[Intrafusal muscle fibers]]
|}

=== {{Visible anchor|Sensory}} === <!-- Sensory fiber types redirects here -->
Different [[sensory receptors]] are innervated by different types of nerve fibers. [[Proprioceptor]]s are innervated by type Ia, Ib and II sensory fibers, [[mechanoreceptor]]s by type II and III sensory fibers and [[nociceptor]]s and [[thermoreceptors]] by type III and IV sensory fibers.

{| class="wikitable"
|+Sensory fiber types
|-
! Type !! Erlanger-Gasser<br />Classification || Diameter<br />(μm) || Myelin || Conduction<br />velocity (m/s) !! Associated [[sensory receptor]]s !! Proprioceptors !! Mechanoceptors !! Nociceptors and<br />thermoreceptors
|-
! [[Type Ia sensory fiber|Ia]]
| Aα || 13–20 || Yes || 80–120 || Primary receptors of [[muscle spindle]] (annulospiral ending) || rowspan="3" align="center" | ✔ || rowspan=2 | || rowspan=3 |
|-
! Ib
| Aα || 13–20 || Yes || 80–120 || [[Golgi tendon organ]]
|-
! [[Type II sensory fiber|II]]
| Aβ || 6–12 || Yes || 33–75 || Secondary receptors of [[muscle spindle]] (flower-spray ending).<br />All [[cutaneous mechanoreceptor]]s|| rowspan="2" align="center" | ✔
|-
! III
| [[A delta fiber|Aδ]] || 1–5 || Thin || 3–30 || [[Free nerve ending]]s of touch and pressure<br />[[Nociceptor]]s of [[lateral spinothalamic tract]]<br />Cold [[thermoreceptors]] ||rowspan=2| || rowspan=2 align=center | ✔
|-
! IV
| [[Group C nerve fiber|C]] || 0.2–1.5 || No || 0.5–2.0 || [[Nociceptor]]s of [[anterior spinothalamic tract]]<br />[[Warmth receptors]] ||
|}

===Autonomic===
The [[autonomic nervous system]] has two kinds of peripheral fibers:

{| class="wikitable"
|+Fiber types
|-
! Type !! Erlanger-Gasser<br />Classification || Diameter<br />(μm) || Myelin<ref>{{cite book |first1=Gillian |last1=Pocock | first2 = Christopher D | last2 = Richards | name-list-style = vanc |title=Human Physiology |location=New York |publisher=Oxford University Press |edition=2nd |year=2004 |pages=187–189 |isbn=978-0-19-858527-5 |display-authors=etal}}</ref> || Conduction<br />velocity (m/s)
|-
! [[preganglionic fibers]]
| B || 1–5 || Yes || 3–15
|-
! [[postganglionic fibers]]
| C || 0.2–1.5 || No || 0.5–2.0
|}

==Clinical significance==
{{Main|Nerve injury |Peripheral neuropathy |Demyelinating disease}}
In order of degree of severity, injury to a nerve in the peripheral nervous system can be described as [[neurapraxia]], [[axonotmesis]], or [[neurotmesis]].
[[Concussion]] is considered a mild form of [[diffuse axonal injury]].<ref>{{cite web |url=https://emedicine.medscape.com/article/326510-overview |title=Traumatic Brain Injury (TBI) - Definition, Epidemiology, Pathophysiology | first = Segun Toyin | last = Dawodu | name-list-style = vanc |date=16 August 2017 |website=Medscape |access-date=14 July 2018 |url-status=live |archive-url=https://web.archive.org/web/20180612184940/https://emedicine.medscape.com/article/326510-overview |archive-date=12 June 2018}}</ref> Axonal injury can also cause [[central chromatolysis]]. The dysfunction of axons in the nervous system is one of the major causes of many inherited and acquired [[neurological disorder]]s that affect both peripheral and central neurons.<ref name="Debanne"/>

When an axon is crushed, an active process of [[Wallerian degeneration#Axonal degeneration|axonal degeneration]] takes place at the part of the axon furthest from the cell body. This degeneration takes place quickly following the injury, with the part of the axon being sealed off at the membranes and broken down by macrophages. This is known as [[Wallerian degeneration]].<ref name="UCSF">[http://missinglink.ucsf.edu/lm/ids_104_cns_injury/Response%20_to_Injury/WallerianDegeneration.htm Trauma and Wallerian Degeneration] {{Webarchive|url=https://web.archive.org/web/20060502020349/http://missinglink.ucsf.edu/lm/ids_104_cns_injury/Response%20_to_Injury/WallerianDegeneration.htm |date=2 May 2006 }}, [[University of California, San Francisco]]</ref> Dying back of an axon can also take place in many [[neurodegenerative disease]]s, particularly when axonal transport is impaired, this is known as Wallerian-like degeneration.<ref name="pmid20345246">{{cite journal | vauthors = Coleman MP, Freeman MR | title = Wallerian degeneration, wld(s), and nmnat | journal = Annual Review of Neuroscience | volume = 33 | issue = 1 | pages = 245–67 | date = 1 June 2010 | pmid = 20345246 | pmc = 5223592 | doi = 10.1146/annurev-neuro-060909-153248 }}</ref> Studies suggest that the degeneration happens as
a result of the axonal protein [[NMNAT2]], being prevented from reaching all of the axon.<ref name="Gilley">{{cite journal | vauthors = Gilley J, Coleman MP | title = Endogenous Nmnat2 is an essential survival factor for maintenance of healthy axons | journal = PLOS Biology | volume = 8 | issue = 1 | pages = e1000300 | date = January 2010 | pmid = 20126265 | pmc = 2811159 | doi = 10.1371/journal.pbio.1000300 | doi-access = free }}</ref>

[[Demyelinating disease|Demyelination of axons]] causes the multitude of neurological symptoms found in the disease [[multiple sclerosis]].

[[Myelin#Dysmyelination|Dysmyelination]] is the abnormal formation of the myelin sheath. This is implicated in several [[leukodystrophy|leukodystrophies]], and also in [[schizophrenia]].<ref>{{cite journal | vauthors = Krämer-Albers EM, Gehrig-Burger K, Thiele C, Trotter J, Nave KA | title = Perturbed interactions of mutant proteolipid protein/DM20 with cholesterol and lipid rafts in oligodendroglia: implications for dysmyelination in spastic paraplegia | journal = The Journal of Neuroscience | volume = 26 | issue = 45 | pages = 11743–52 | date = November 2006 | pmid = 17093095 | pmc = 6674790 | doi = 10.1523/JNEUROSCI.3581-06.2006 }}</ref><ref>{{Cite book|vauthors=Matalon R, Michals-Matalon K, Surendran S, Tyring SK |chapter=Canavan Disease: Studies on the Knockout Mouse |title=N-Acetylaspartate |s2cid=44405442 |volume=576 |pages=77–93; discussion 361–3 |year=2006 |pmid=16802706 |doi=10.1007/0-387-30172-0_6 |series=Advances in Experimental Medicine and Biology |isbn=978-0-387-30171-6}}</ref><ref>{{cite journal | vauthors = Tkachev D, Mimmack ML, Huffaker SJ, Ryan M, Bahn S | title = Further evidence for altered myelin biosynthesis and glutamatergic dysfunction in schizophrenia | journal = The International Journal of Neuropsychopharmacology | volume = 10 | issue = 4 | pages = 557–63 | date = August 2007 | pmid = 17291371 | doi = 10.1017/S1461145706007334 | doi-access = free }}</ref>

A severe [[traumatic brain injury]] can result in widespread lesions to nerve tracts damaging the axons in a condition known as [[diffuse axonal injury]]. This can lead to a [[persistent vegetative state]].<ref name="Healthcare">{{cite web|url=http://www.medcyclopaedia.com/library/topics/volume_vi_1/b/BRAIN_INJURY_TRAUMATIC.aspx|archive-url=https://archive.today/20110526162429/http://www.medcyclopaedia.com/library/topics/volume_vi_1/b/BRAIN_INJURY_TRAUMATIC.aspx|url-status=dead|archive-date=26 May 2011|title=Brain Injury, Traumatic|publisher=[[General Electric|GE]]|website=Medcyclopaedia|access-date=20 June 2018}}</ref> It has been shown in studies on the [[rat]] that axonal damage from a single mild traumatic brain injury, can leave a susceptibility to further damage, after repeated mild traumatic brain injuries.<ref>{{cite journal | vauthors = Wright DK, Brady RD, Kamnaksh A, Trezise J, Sun M, McDonald SJ, Mychasiuk R, Kolbe SC, Law M, Johnston LA, O'Brien TJ, Agoston DV, Shultz SR | display-authors = 6 | title = Repeated mild traumatic brain injuries induce persistent changes in plasma protein and magnetic resonance imaging biomarkers in the rat | journal = Scientific Reports | volume = 9 | issue = 1 | pages = 14626 | date = October 2019 | pmid = 31602002 | pmc = 6787341 | doi = 10.1038/s41598-019-51267-w | bibcode = 2019NatSR...914626W }}</ref>

A [[nerve guidance conduit]] is an artificial means of guiding axon growth to enable [[neuroregeneration]], and is one of the many treatments used for different kinds of [[nerve injury]].

== Terminology ==
Some general dictionaries define "nerve fiber" as any [[Neurite|neuronal process]], including both axons and [[dendrite]]s.<ref>{{Cite web |title=nerve fiber |url=https://www.merriam-webster.com/dictionary/nerve+fiber |access-date=2023-04-21 |website=Merriam-Webster |language=en}}</ref><ref>{{Cite web |title=nerve fibre |url=https://www.oed.com/view/Entry/126203#eid35153231 |access-date=2023-04-21 |website=[[Oxford English Dictionary]] |language=en}}</ref> However, medical sources generally use "nerve fiber" to refer to the axon only.<ref>{{Cite web |title=nerve fiber |url=https://www.tabers.com/tabersonline/view/Tabers-Dictionary/753758/all/nerve_fiber?refer=true |access-date=2023-04-21 |website=[[Taber's Medical Dictionary]] |language=en}}</ref><ref>{{Cite web |title=nerve fiber |url=https://dictionary.apa.org/ |access-date=2023-04-21 |website=APA Dictionary of Psychology |publisher=[[American Psychological Association]] |language=en}}</ref>

==History==
German anatomist [[Otto Friedrich Karl Deiters]] is generally credited with the discovery of the axon by distinguishing it from the dendrites.<ref name="Debanne" /> Swiss [[Albert von Kölliker|Rüdolf Albert von Kölliker]] and German [[Robert Remak]] were the first to identify and characterize the axon initial segment. Kölliker named the axon in 1896.<ref>{{cite book |title=Origins of neuroscience: a history of explorations into brain function| last=Finger |first=Stanley | name-list-style = vanc |publisher=Oxford University Press|year=1994|isbn=9780195146943|pages=47|oclc=27151391|quote=Kölliker would give the "axon" its name in 1896.}}</ref> [[Louis-Antoine Ranvier]] was the first to describe the gaps or nodes found on axons and for this contribution these axonal features are now commonly referred to as the [[Node of Ranvier|nodes of Ranvier]]. [[Santiago Ramón y Cajal]], a Spanish anatomist, proposed that axons were the output components of neurons, describing their functionality.<ref name="Debanne" /> [[Joseph Erlanger]] and [[Herbert Gasser]] earlier developed the classification system for peripheral nerve fibers,<ref>{{cite journal | vauthors = Grant G | title = The 1932 and 1944 Nobel Prizes in physiology or medicine: rewards for ground-breaking studies in neurophysiology | journal = Journal of the History of the Neurosciences | volume = 15 | issue = 4 | pages = 341–57 | date = December 2006 | pmid = 16997762 | doi = 10.1080/09647040600638981 | s2cid = 37676544 }}</ref> based on axonal conduction velocity, [[myelin]]ation, fiber size etc. [[Alan Hodgkin]] and [[Andrew Huxley]] also employed the squid giant axon (1939) and by 1952 they had obtained a full quantitative description of the ionic basis of the action potential, leading to the formulation of the [[Hodgkin–Huxley model]]. Hodgkin and Huxley were awarded jointly the [[Nobel Prize in Physiology or Medicine|Nobel Prize]] for this work in 1963. The formulae detailing axonal conductance were extended to vertebrates in the Frankenhaeuser–Huxley equations. The understanding of the biochemical basis for action potential propagation has advanced further, and includes many details about individual [[ion channel]]s.

==Other animals==
The axons in [[invertebrate]]s have been extensively studied. The [[longfin inshore squid]], often used as a [[model organism]] has the longest known axon.<ref name="Hellier">{{Cite book|last1=Hellier|first1=Jennifer L.|title=The Brain, the Nervous System, and Their Diseases [3 volumes]|url=https://books.google.com/books?id=SDi2BQAAQBAJ&q=axon|publisher=ABC-CLIO|language=en|date=16 December 2014|url-status=live|archive-url=https://web.archive.org/web/20180314180028/https://books.google.co.uk/books?redir_esc=y&id=SDi2BQAAQBAJ&q=axon |archive-date=14 March 2018|isbn=9781610693387}}</ref> The [[giant squid]] has the largest axon known. Its size ranges from 0.5 (typically) to 1&nbsp;mm in diameter and is used in the control of its [[jet propulsion]] system. The fastest recorded conduction speed of 210&nbsp;m/s, is found in the ensheathed axons of some pelagic [[Penaeidae|Penaeid shrimp]]s<ref>{{cite journal | vauthors = Hsu K, Terakawa S | title = Fenestration in the myelin sheath of nerve fibers of the shrimp: a novel node of excitation for saltatory conduction | journal = Journal of Neurobiology | volume = 30 | issue = 3 | pages = 397–409 | date = July 1996 | pmid = 8807532 | doi = 10.1002/(SICI)1097-4695(199607)30:3<397::AID-NEU8>3.0.CO;2-# }}</ref> and the usual range is between 90 and 200&nbsp;meters/s<ref name=Salzer>{{cite journal | vauthors = Salzer JL, Zalc B | title = Myelination | journal = Current Biology | volume = 26 | issue = 20 | pages = R971–R975 | date = October 2016 | pmid = 27780071 | doi = 10.1016/j.cub.2016.07.074 | doi-access = free | bibcode = 2016CBio...26.R971S }}</ref> ([[Cf.|cf]] 100–120&nbsp;m/s for the fastest myelinated vertebrate axon.)

==Additional images==
<gallery>
File:Example of Waveforms from Extracellular Tetrode Recordings in the Hippocampus from Different Cell Types and Axons.tif|Recordings in the hippocampus from different cell types and axons
</gallery>

== See also ==
* [[Electrophysiology]]
* [[Ganglionic eminence]]
* [[Giant axonal neuropathy]]
* [[Neuronal tracing]]
* [[Pioneer axon]]
* [[Single-unit recording]]

== References ==
{{Reflist}}

== External links ==
* {{OklahomaHistology|3_09}}{{Snd}}"Slide 3 [[Spinal cord]]"

{{Nervous tissue}}

{{Authority control}}

[[Category:Neurohistology]]