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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 Vertebrate, that typically conducts electrical impulses known as away from the nerve cell body. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain (pseudounipolar neurons), such as those for touch and warmth, the axons are called afferent nerve fibers and the electrical impulse travels along these from the 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 disorders that affect both the peripheral and central neurons. Nerve fibers are classed into three typesgroup A nerve fibers, group B nerve fibers, and group C nerve fibers. Groups A and B are , 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 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. 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 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 connection. Axons usually make contact with other neurons at junctions called 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 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. (2025). 9780123858702, Elsevier/Academic Press. ISBN 9780123858702 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, and a nerve fascicle in the peripheral nervous system. In Placentalia the largest white matter tract in the brain is the corpus callosum, formed of some 200 million axons in the human brain.
There are two types of axons in the nervous system: and unmyelinated axons. Myelin is a layer of a fatty insulating substance, which is formed by two types of neuroglia: and . 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 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 commissures. The largest of these is the corpus callosum that connects the two cerebral hemispheres, and this has around 20 million axons.
The structure of a neuron is seen to consist of two separate functional regions, or compartmentsthe cell body together with the dendrites as one region, and the axonal region as the other.
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. This is achieved by a high concentration of 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 that anchor them to the cytoskeleton. Interactions with ankyrin-G are important as it is the major organizer in the AIS.
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.
Outgoing anterograde transport from the cell body along the axon, carries mitochondria and needed for growth to the axon terminal. Ingoing retrograde transport carries cell waste materials from the axon terminal to the cell body.
In the peripheral nervous system axons are myelinated by neuroglia known as . 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.
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.
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 (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 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 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 (~500μs) or (~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 potentials in vivo is sequential in nature, and these sequential spikes constitute the neural coding 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.Rongjing Ge, Hao Qian and Jin-Hui Wang* (2011) Molecular Brain 4(19), 1~11Rongjing Ge, Hao Qian, Na Chen and Jin-Hui Wang* (2014) Molecular Brain 7(26):1-16
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 and shorter refractory period in response to short-term pulses.
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.
Cells called guidepost cells assist in the axon 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 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) 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.
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 activated through a specific inflammatory pathway activated by the Dectin-1 receptor are capable of promoting axon recovery, also however causing neurotoxicity in the neuron.
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, group B, and group C include both the sensory fibers (afferents) and the motor fibers (efferents). The first group A, was subdivided into alpha, beta, gamma, and delta fibersAα, Aβ, Aγ, and Aδ. The of the different motor fibers, were the lower motor neuronsalpha 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.
When an axon is crushed, an active process of 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.
Demyelination of axons causes the multitude of neurological symptoms found in the disease multiple sclerosis.
Dysmyelination is the abnormal formation of the myelin sheath. This is implicated in several leukodystrophy, 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.
==Additional images==
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 directiontowards 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 filamentsthe microtubules, and , in both directions between the axon and its terminals and the cell body.
(2025). 9780815340720, Garland. ISBN 9780815340720 Outgoing and ingoing tracks use different sets of . 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
[[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 , 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.
Nodes of Ranvier
Nodes of Ranvier (also known as myelin sheath gaps) are short unmyelinated segments of a myelin, 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, 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 for 'end of tree'). At the end of each telodendron is an axon terminal (also called a terminal bouton or synaptic bouton, or ). Axon terminals contain that store the neurotransmitter for release at the Chemical 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. (2025). 9780123858702, Elsevier/Academic Press. ISBN 9780123858702
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. 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. 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.
Action potentials
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"every action potential that an axon generates has essentially the same size and shape. This All-or-none law 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.
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. (2025). 9780199678143, Oxford University Press. ISBN 9780199678143 Studies done on cultured hippocampus neurons suggest that neurons initially produce multiple 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 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 express UNC-6 to provide global and local netrin cues for guiding migrations in C. elegans The neurotrophic factorsnerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NTF3) are also involved in axon development and bind to .
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 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 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-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 CAMs specific to neural systems include N-CAM, TAG-1an axonal glycoproteinand MAG, all of which are part of the immunoglobulin superfamily. Another set of molecules called extracellular matrix-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.
(2025). 9780815344643 ISBN 9780815344643
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 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 axonits conductance velocity. Joseph Erlanger and 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.
Motor
Lower motor neurons have two kind of fibers:
+Motor fiber types
Different sensory receptors are innervated by different types of nerve fibers. are innervated by type Ia, Ib and II sensory fibers, by type II and III sensory fibers and and thermoreceptors by type III and IV sensory fibers.
+Sensory fiber types
Autonomic
The autonomic nervous system has two kinds of peripheral fibers:
+Fiber types
Clinical significance
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. 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 disorders that affect both peripheral and central neurons.
(2025). 9780387301716 ISBN 9780387301716
Terminology
Some general dictionaries define "nerve fiber" as any Neurite, including both axons and . However, medical sources generally use "nerve fiber" to refer to the axon only.
History
German anatomist Otto Friedrich Karl Deiters is generally credited with the discovery of the axon by distinguishing it from the dendrites. Swiss 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 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, , 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 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 .
Other animals
The axons in have been extensively studied. The longfin inshore squid, often used as a model organism has the longest known axon. The giant squid has the largest axon known. Its size ranges from 0.5 (typically) to 1 mm 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 and the usual range is between 90 and 200 meters/s (cf 100–120 m/s for the fastest myelinated vertebrate axon.)
See also
External links
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