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An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see
spelling differences Despite the various English dialects spoken from country to country and within different regions of the same country, there are only slight regional variations in English orthography, the two most notable variations being British and America ...
), is a long, slender projection of a nerve cell, or
neuron A neuron or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. It is the main component of nervous tissue in all animals except sponges and placozoa. Plants and fungi do ...

neuron
, in vertebrates, that typically conducts electrical impulses known as
action potential In physiology, an action potential (AP) occurs when the membrane potential of a specific cell location rapidly rises and falls: this depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types ...

action potential
s away from the nerve cell body. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain
sensory neuron Sensory neurons, also known as afferent neurons, are neurons in the nervous system, that convert a specific type of stimulus, via their receptors, into action potentials or graded potentials. This process is called sensory transduction. The cell ...
s (
pseudounipolar neuron A pseudounipolar neuron is a type of neuron which has one extension from its cell body. This type of neuron contains an axon that has split into two branches; one branch travels to the peripheral nervous system and the other to the central nervous ...
s), such as those for touch and warmth, the axons are called
afferent nerve fiber Afferent nerve fibers refer to axonal projections that ''arrive'' at a particular brain region, as opposed to efferent projections that ''exit'' the region. These terms have a slightly different meaning in the context of the peripheral nervous ...
s and the electrical impulse travels along these from the
periphery Periphery or Peripheral may refer to: *Periphery (band), American progressive metal band *''Periphery'' (album), released in 2010 by Periphery *Periphery, a group of political entities in BattleTech, a wargaming franchise *Periphery countries, the ...
to the cell body, and from the cell body to the spinal cord along another branch of the same axon. Axon dysfunction has caused many inherited and acquired neurological disorders which can affect both the peripheral and central neurons. Nerve fibers are classed into three types –
group A nerve fiber Group A nerve fibers are one of the three classes of nerve fiber as ''generally classified'' by Erlanger and Gasser. The other two classes are the group B nerve fibers, and the group C nerve fibers. Group A are heavily myelinated, group B are mo ...
s,
group B nerve fiber Group B nerve fibers are axons, which are moderately myelinated, which means less myelinated than group A nerve fibers, and more myelinated than group C nerve fibers. Their conduction velocity is 3 to 14 m/s. They are usually general visceral affere ...
s, and
group C nerve fiber Group C nerve fibers are one of three classes of nerve fiber in the central nervous system (CNS) and peripheral nervous system (PNS). The C group fibers are unmyelinated and have a small diameter and low conduction velocity, whereas Groups A and ...
s. Groups A and B are
myelin Myelin is a lipid-rich (fatty) substance that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon c ...
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
cytoplasm In cell biology, the cytoplasm is all of the material within a cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The main compone ...
ic protrusions from the cell body of a neuron; the other type is a
dendrite Dendrites (from Greek δένδρον ''déndron'', "tree"), also dendrons, are branched protoplasmic extensions of a nerve cell that propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neu ...
. 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. 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. Axons are covered by a membrane known as an
axolemma The axolemma is the cell membrane of an axon. The similar term axoplasm refers to the cytoplasm of an axon. The axolemma is responsible for maintaining the membrane potential of the axon, and contains ion channels through which ions can flow rapid ...
; the cytoplasm of an axon is called
axoplasm Axoplasm is the cytoplasm within the axon of a neuron (nerve cell). For some neuronal types this can be more than 99% of the total cytoplasm. Axoplasm has a different composition of organelles and other materials than that found in the neuron's ce ...
. Most axons branch, in some cases very profusely. The end branches of an axon are called
telodendria An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action pot ...
. The swollen end of a telodendron is known as the
axon terminal Axon terminals (also called synaptic boutons, terminal boutons, or end-feet) are distal terminations of the telodendria (branches) of an axon. An axon, also called a nerve fiber, is a long, slender projection of a nerve cell, or neuron, that conduc ...
which joins the dendron or cell body of another neuron forming a synaptic connection. Axons make contact with other cells—usually other neurons but sometimes muscle or gland cells—at junctions called
synapse SyNAPSE is a DARPA program that aims to develop electronic neuromorphic machine technology, an attempt to build a new kind of cognitive computer with form, function, and architecture similar to the mammalian brain. Such artificial brains would be u ...
s. In some circumstances, the axon of one neuron may form a synapse with the dendrites of the same neuron, resulting in an
autapseAn autapse is a chemical or electrical synapse from a neuron onto itself. It can also be described as a synapse formed by the axon of a neuron on its own dendrites, ''in vivo'' or ''in vitro''. History The term "autapse" was first coined in 1972 by ...
. At a synapse, the
membrane up150px, Schematic of size-based membrane exclusion A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Biological membranes include cell membranes ...
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'' ("in passing") synapses and can be in the hundreds or even the thousands along one axon. Other synapses appear as terminals at the ends of axonal branches. A single axon, with all its branches taken together, can
innervate A nerve is an enclosed, cable-like bundle of nerve fibers called axons, in the peripheral nervous system. A nerve transmits electrical impulses and is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the elect ...
multiple parts of the brain and generate thousands of synaptic terminals. A bundle of axons make a
nerve tract A nerve tract is a bundle of nerve fibers (axons) connecting nuclei of the central nervous system. In the peripheral nervous system this is known as a nerve, and has associated connective tissue. The main nerve tracts in the central nervous system ...
in the
central nervous system#REDIRECT Central nervous system#REDIRECT Central nervous system {{Redirect category shell, 1= {{R from other capitalisation ...
{{Redirect category shell, 1= {{R from other capitalisation ...

central nervous system
, and a fascicle in the
peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of the nerves and ganglia outside the brain and spinal ...
. In
placental mammals Placentalia is one of the three extant subdivisions of the class of animals Mammalia; the other two are Monotremata and Marsupialia. The placentals are partly distinguished from other mammals in that the fetus is carried in the uterus of its mot ...
the largest
white matter White matter refers to areas of the central nervous system (CNS) that are mainly made up of myelinated axons, also called tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distribution o ...
tract in the brain is the
corpus callosum The corpus callosum (Latin for "tough body"), also callosal commissure, is a wide, thick nerve tract, consisting of a flat bundle of commissural fibers, beneath the cerebral cortex in the brain. The corpus callosum is only found in placental mamm ...

corpus callosum
, formed of some 200 million axons in the
human brain The human brain is the central organ of the human nervous system, and with the spinal cord makes up the central nervous system. The brain consists of the cerebrum, the brainstem and the cerebellum. It controls most of the activities of the body ...

human brain
.


Anatomy

Axons are the primary transmission lines of the
nervous system In biology, the nervous system is a highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes that im ...
, and as bundles they form
nerve A nerve is an enclosed, cable-like bundle of nerve fibers called axons, in the peripheral nervous system. A nerve transmits electrical impulses and is the basic unit of the peripheral nervous system. A nerve provides a common pathway for the elect ...
s. 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 The sciatic nerve, also called the ischiadic nerve, is a large nerve in humans and other vertebrate animals which is the largest branch of the sacral plexus and runs alongside the hip joint and down the lower limb. It is the longest and widest sin ...
, which run from the base of the
spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column. It encloses the central canal of the spinal cord, which contains ...
to the big toe of each foot. The diameter of axons is also variable. Most individual axons are microscopic in diameter (typically about one
micrometer A micrometer, sometimes known as a micrometer screw gauge, is a device incorporating a calibrated screw widely used for accurate measurement of components in mechanical engineering and machining as well as most mechanical trades, along with othe ...
(µm) across). The largest mammalian axons can reach a diameter of up to 20 µm. The
squid giant axon The squid giant axon is the very large (up to 1.5 mm in diameter; typically around 0.5 mm) axon that controls part of the water jet propulsion system in squid. It was first described by L. W. Williams in 1909, but this discovery was forg ...
, which is specialized to conduct signals very rapidly, is close to 1
millimetre The millimetre (international spelling; SI unit symbol mm) or millimeter (American spelling) is a unit of length in the metric system, equal to one thousandth of a metre, which is the SI base unit of length. Therefore, there are one thousand mill ...
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
central nervous system#REDIRECT Central nervous system#REDIRECT Central nervous system {{Redirect category shell, 1= {{R from other capitalisation ...
{{Redirect category shell, 1= {{R from other capitalisation ...

central nervous system (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 Cerebellar granule cells form the thick granular layer of the cerebellar cortex and are among the smallest neurons in the brain. (The term granule cell is used for several unrelated types of small neurons in various parts of the brain.) Cerebe ...
s extend. Elaborate branching allows for the simultaneous transmission of messages to a large number of target neurons within a single region of the brain. There are two types of axons in the
nervous system In biology, the nervous system is a highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes that im ...
:
myelin Myelin is a lipid-rich (fatty) substance that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon c ...
ated and
unmyelinated Myelin is a lipid-rich (fatty) substance that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon c ...
axons.
Myelin Myelin is a lipid-rich (fatty) substance that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon c ...
is a layer of a fatty insulating substance, which is formed by two types of
glial cells Glia, also called glial cells or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myelin, and provi ...

glial cells
:
Schwann cell Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory enshea ...
s and
oligodendrocyte Oligodendrocytes (), or oligodendroglia, are a type of neuroglia whose main functions are to provide support and insulation to axons in the central nervous system of some vertebrates, equivalent to the function performed by Schwann cells in the per ...
s. In the
peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of the nerves and ganglia outside the brain and spinal ...
Schwann cells form the myelin sheath of a myelinated axon. In the
central nervous system#REDIRECT Central nervous system#REDIRECT Central nervous system {{Redirect category shell, 1= {{R from other capitalisation ...
{{Redirect category shell, 1= {{R from other capitalisation ...

central nervous system oligodendrocytes form the insulating myelin. Along myelinated nerve fibers, gaps in the myelin sheath known as
nodes of Ranvier Nodes of Ranvier ( , ), also known as myelin-sheath gaps, occur along a myelinated axon where the axolemma is exposed to the extracellular space. Nodes of Ranvier are uninsulated and highly enriched in ion channels, allowing them to participate i ...
occur at evenly spaced intervals. The myelination enables an especially rapid mode of electrical impulse propagation called
saltatory conduction Saltatory conduction (from the Latin ''saltare'', to hop or leap) is the propagation of action potentials along myelinated axons from one node of Ranvier to the next node, increasing the conduction velocity of action potentials. The uninsulated ...

saltatory conduction
. The myelinated axons from the cortical neurons form the bulk of the neural tissue called
white matter White matter refers to areas of the central nervous system (CNS) that are mainly made up of myelinated axons, also called tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distribution o ...
in the brain. The myelin gives the white appearance to the tissue in contrast to the
grey matter Grey matter (or gray matter) is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil (dendrites and unmyelinated axons), glial cells (astrocytes and oligodendrocytes), synapses, and capillaries. Grey matt ...
of the cerebral cortex which contains the neuronal cell bodies. A similar arrangement is seen in the
cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...

cerebellum
. Bundles of myelinated axons make up the
nerve tract A nerve tract is a bundle of nerve fibers (axons) connecting nuclei of the central nervous system. In the peripheral nervous system this is known as a nerve, and has associated connective tissue. The main nerve tracts in the central nervous system ...
s in the CNS. Where these tracts cross the midline of the brain to connect opposite regions they are called ''commissures''. The largest of these is the
corpus callosum The corpus callosum (Latin for "tough body"), also callosal commissure, is a wide, thick nerve tract, consisting of a flat bundle of commissural fibers, beneath the cerebral cortex in the brain. The corpus callosum is only found in placental mamm ...

corpus callosum
that connects the two
cerebral hemisphere The vertebrate cerebrum (brain) is formed by two cerebral hemispheres that are separated by a groove, the longitudinal fissure. The brain can thus be described as being divided into left and right cerebral hemispheres. Each of these hemispheres h ...
s, and this has around 20 million axons. The structure of a neuron is seen to consist of two separate functional regions, or compartments – 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 hippocampus showing various classes of cells (neurons and glia). Image:Gray626.png, 200px, Motor nerve cell from ventral horn of medulla spinalis of rabbit. The angular and spindle-shaped Nissl bodies are well shown. A Nissl body, also known as Nissl ...
that produce the neuronal proteins are absent in the axonal region. Proteins needed for the growth of the axon, and the removal of waste materials, need a framework for transport. This
axonal transportAxonal transport, also called axoplasmic transport or axoplasmic flow, is a cellular process responsible for movement of mitochondria, lipids, synaptic vesicles, proteins, and other organelles to and from a neuron's cell body, through the cytoplasm o ...
is provided for in the axoplasm by arrangements of microtubules and intermediate filaments known as neurofilaments.


Axon hillock

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 potentials 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.


Initial segment

The axonal initial segment (AIS) is a structurally and functionally separate microdomain of the axon. 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 potential In physiology, an action potential (AP) occurs when the membrane potential of a specific cell location rapidly rises and falls: this depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types ...

action potential
s. 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. The axon initial segment is unmyelinated and contains a specialized complex of proteins. It is between approximately 20 and 60 µm in length and functions as the site of action potential initiation. 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. A longer AIS is associated with a greater excitability. 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. The AIS is highly specialized for the fast conduction of Action potential, nerve impulses. This is achieved by a high concentration of Sodium channel#Voltage-gated sodium channel, voltage-gated sodium channels in the initial segment where the action potential is initiated. The ion channels are accompanied by a high number of cell adhesion molecules and scaffolding proteins that anchor them to the cytoskeleton. Interactions with Ankyrin-G binding motif of KCNQ2-3, ankyrin G are important as it is the major organizer in the AIS.


Axonal transport

The
axoplasm Axoplasm is the cytoplasm within the axon of a neuron (nerve cell). For some neuronal types this can be more than 99% of the total cytoplasm. Axoplasm has a different composition of organelles and other materials than that found in the neuron's ce ...
is the equivalent of
cytoplasm In cell biology, the cytoplasm is all of the material within a cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The main compone ...
in the cell (biology), 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 – towards the axon terminals. 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. Studies on the axoplasm has shown the movement of numerous vesicles of all sizes to be seen along cytoskeletal filaments – the microtubules, and neurofilaments, 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 proteins 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. Outgoing and ingoing tracks use different sets of motor proteins. Outgoing transport is provided by kinesin, and ingoing return traffic is provided by dynein. Dynein is minus-end directed. There are many forms of kinesin and dynein motor proteins, and each is thought to carry a different cargo. The studies on transport in the axon led to the naming of kinesin.


Myelination

In the nervous system, axons may be
myelin Myelin is a lipid-rich (fatty) substance that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon c ...
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. In the peripheral nervous system axons are myelinated by
glial cells Glia, also called glial cells or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myelin, and provi ...

glial cells
known as
Schwann cell Schwann cells or neurolemmocytes (named after German physiologist Theodor Schwann) are the principal glia of the peripheral nervous system (PNS). Glial cells function to support neurons and in the PNS, also include satellite cells, olfactory enshea ...
s. In the central nervous system the myelin sheath is provided by another type of glial cell, the
oligodendrocyte Oligodendrocytes (), or oligodendroglia, are a type of neuroglia whose main functions are to provide support and insulation to axons in the central nervous system of some vertebrates, equivalent to the function performed by Schwann cells in the per ...
. Schwann cells myelinate a single axon. An oligodendrocyte can myelinate up to 50 axons. 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

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. These nodes are areas where action potentials can be generated. In
saltatory conduction Saltatory conduction (from the Latin ''saltare'', to hop or leap) is the propagation of action potentials along myelinated axons from one node of Ranvier to the next node, increasing the conduction velocity of action potentials. The uninsulated ...

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

An axon can divide into many branches called telodendria (Greek–end of tree). At the end of each telodendron is an
axon terminal Axon terminals (also called synaptic boutons, terminal boutons, or end-feet) are distal terminations of the telodendria (branches) of an axon. An axon, also called a nerve fiber, is a long, slender projection of a nerve cell, or neuron, that conduc ...
(also called a synaptic bouton, or terminal bouton). Axon terminals contain synaptic vesicles 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
autapseAn autapse is a chemical or electrical synapse from a neuron onto itself. It can also be described as a synapse formed by the axon of a neuron on its own dendrites, ''in vivo'' or ''in vitro''. History The term "autapse" was first coined in 1972 by ...
.


Action potentials

Most axons carry signals in the form of
action potential In physiology, an action potential (AP) occurs when the membrane potential of a specific cell location rapidly rises and falls: this depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types ...

action potential
s, which are discrete electrochemical impulses that travel rapidly along an axon, starting at the cell body and terminating at points where the axon makes chemical synapse, synaptic contact with target cells. The defining characteristic of an action potential is that it is "all-or-nothing" — every action potential that an axon generates has essentially the same size and shape. This 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 vesicles (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. Extracellular recordings of
action potential In physiology, an action potential (AP) occurs when the membrane potential of a specific cell location rapidly rises and falls: this depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types ...

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 cells (~500μs) or interneurons (~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. In fact, the generation of
action potential In physiology, an action potential (AP) occurs when the membrane potential of a specific cell location rapidly rises and falls: this depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types ...

action potential
s in vivo is sequential in nature, and these sequential spikes constitute the neural coding, digital codes in the
neuron A neuron or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. It is the main component of nervous tissue in all animals except sponges and placozoa. Plants and fungi do ...

neuron
s. 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. 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 channels in the axons possess lower Threshold potential, threshold and shorter Refractory period (physiology), refractory period in response to short-term pulses.


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. Studies done on cultured hippocampus, hippocampal neurons suggest that neurons initially produce multiple neurites that are equivalent, yet only one of these neurites is destined to become the axon. It is unclear whether axon specification precedes axon elongation or vice versa, 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. Imposing an external force on a neurite, causing it to elongate, will make it become an axon. 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. 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.Neuroglia and pioneer neurons express UNC-6 to provide global and local netrin cues for guiding migrations in Caenorhabditis elegans, ''C. elegans'' The neurotrophic factors – nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NTF3) are also involved in axon development and bind to Trk receptors. 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.


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 phosphatases that dephosphorylate PtdIns leads into the failure of polarization.


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. 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.


Growth

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 molecules (CAMs) create an ideal environment for axonal growth. This seems to provide a "sticky" surface for axons to grow along. Examples of CAM's specific to neural systems include Neural Cell Adhesion Molecule, N-CAM, Contactin 2, TAG-1—an axonal glycoprotein——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 molecules 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. 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 A neuron or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. It is the main component of nervous tissue in all animals except sponges and placozoa. Plants and fungi do ...

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. 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. A recent study has also found that macrophages 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.


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. 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. 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

The axons of neurons in the human
peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of the nerves and ganglia outside the brain and spinal ...
can be classified based on their physical features and signal conduction properties. Axons were known to have different thicknesses (from 0.1 to 20 µm) and these differences were thought to relate to the speed at which an action potential could travel along the axon – 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 fibres (efferent nerve fiber, efferents). The first group A, was subdivided into alpha, beta, gamma, and delta fibers — Aα, Aβ, Aγ, and Aδ. The motor neurons of the different motor fibers, were the lower motor neurons – 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 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.


Lower motor neurons have two kind of fibers:


Different sensory receptors innervate different types of nerve fibers. Proprioceptors are innervated by type Ia, Ib and II sensory fibers, mechanoreceptors by type II and III sensory fibers and nociceptors and thermoreceptors by type III and IV sensory fibers.


Autonomic

The autonomic nervous system has two kinds of peripheral fibers:


Clinical significance

In order of degree of severity, injury to a nerve can be described as neurapraxia, axonotmesis, or neurotmesis. Concussion is considered a mild form of diffuse axonal injury. Axonal injury can also cause central chromatolysis. The dysfunction of axons in the nervous system is one of the major causes of many inherited neurological disorders that affect both peripheral and central neurons. 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.Trauma and Wallerian Degeneration
, University of California, San Francisco
Dying back of an axon can also take place in many neurodegenerative diseases, particularly when axonal transport is impaired, this is known as Wallerian-like degeneration. Studies suggest that the degeneration happens as a result of the axonal protein NMNAT2, being prevented from reaching all of the axon. 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. 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. 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. 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.


History

German anatomist Otto Friedrich Karl Deiters is generally credited with the discovery of the axon by distinguishing it from the dendrites. 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. 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. Joseph Erlanger and Herbert Gasser earlier developed the classification system for peripheral nerve fibers, based on axonal conduction velocity,
myelin Myelin is a lipid-rich (fatty) substance that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon c ...
ation, fiber size etc. Alan Hodgkin and Andrew Huxley also employed the
squid giant axon The squid giant axon is the very large (up to 1.5 mm in diameter; typically around 0.5 mm) axon that controls part of the water jet propulsion system in squid. It was first described by L. W. Williams in 1909, but this discovery was forg ...
(1939) and by 1952 they had obtained a full quantitative description of the ionic basis of the
action potential In physiology, an action potential (AP) occurs when the membrane potential of a specific cell location rapidly rises and falls: this depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types ...

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 channels.


Other animals

The axons in invertebrates have been extensively studied. The longfin inshore squid, often used as a model organism has the longest known axon. The giant squid has the squid giant axon, largest axon known. Its size ranges from a half (typically) to one millimetre in diameter and is used in the control of its jet propulsion system. The fastest recorded conduction speed of 210 m/s, is found in the ensheathed axons of some pelagic Penaeidae, Penaeid shrimps and the usual range is between 90 and 200 m/s (Cf., cf 100–120 m/s for the fastest myelinated vertebrate axon.) 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. 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. 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.


See also

*Electrophysiology *Ganglionic eminence *Giant axonal neuropathy *Neuronal tracing *Pioneer axon


References


External links

*  — "Slide 3 Spinal cord" {{Authority control Neurohistology