Axon

An axon (from Greek ἄξων áxōn, axis), or nerve fiber, is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action potentials away from the nerve cell body. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain sensory neurons (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 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 fibers, group B nerve fibers, and group C nerve fibers. Groups A and B are myelinated, 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 and these are known as axon-carrying dendrites.[1] 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.[2]

Axons are covered by a membrane known as an axolemma; the cytoplasm of 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 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 synapses. 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 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 ("in passing") synapses and can be in the hundreds or even the thousands along one axon.[3] Other synapses appear as terminals at the ends of axonal branches.

A single axon, with all its branches taken together, can innervate multiple parts of the brain and generate thousands of synaptic terminals. A bundle of axons make a nerve tract in the central nervous system,[4] and a fascicle in the peripheral nervous system. In placental mammals the largest white matter tract in the brain is the corpus callosum, formed of some 20 million axons in the human brain.[4]

Axon
Blausen 0657 MultipolarNeuron
An axon of a multipolar neuron
Identifiers
MeSHD001369
Anatomical terminology

Anatomy

Neuron
A typical myelinated axon
Human brain right dissected lateral view description
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 nerves. 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 micrometer (µm) across). The largest mammalian axons can reach a diameter of up to 20 µm. The squid giant axon, which is specialized to conduct signals very rapidly, is close to 1 millimetre 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 (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 fibers 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: myelinated and unmyelinated axons.[5] Myelin is a layer of a fatty insulating substance, which is formed by two types of glial cells Schwann cells and oligodendrocytes. In the peripheral nervous system Schwann cells form the myelin sheath of a myelinated axon. In the central nervous system oligodendrocytes form the insulating myelin. 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 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. 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 that connects the two cerebral hemispheres, and this has around 20 million axons.[4]

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 that produce the neuronal proteins are absent in the axonal region.[3] 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.

Axon hillock

Neuron Cell Body
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 potentials that are 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.[6][7] 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.[8] Both of these functions support neuron cell polarity, in which dendrites (and, in some cases, soma) of a neuron receive input signals and the neuron's axon provides output signals.[9]

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.[10][11] 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.[10][12] A longer AIS is associated with a greater excitability.[12] 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.[13]

The AIS is highly specialized for the fast conduction of nerve impulses. This is achieved by a high concentration of voltage-gated sodium channels in the initial segment where the action potential is initiated.[13] The ion channels are accompanied by a high number of cell adhesion molecules and scaffolding proteins that anchor them to the cytoskeleton.[10] Interactions with ankyrin G are important as it is the major organizer in the AIS.[10]

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 – towards the axon terminals.[14] 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.[14] 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 anterograde transport from the cell body along the axon, carries mitochondria and membrane proteins needed for growth to the axon terminal. Ingoing retrograde transport carries cell waste materials from the axon terminal to the cell body.[15] Outgoing and ingoing tracks use different sets of motor proteins.[14] Outgoing transport is provided by kinesin, and ingoing return traffic is provided by dynein. Dynein is minus-end directed.[15] There are many forms of kinesis and dynein motor proteins, and each is thought to carry a different cargo.[14] The studies on transport in the axon led to the naming of kinesin.[14]

Myelination

Myelinated neuron
Transmission electron micrograph of a myelinated axon in cross-section. Generated by the electron microscopy unit at Trinity College, Hartford CT
Myelin sheath (1)
Cross section of an axon.
1. Axon
2. Nucleus of Schwann cell
3. Schwann cell
4. Myelin sheath
5. Neurilemma

In the nervous system, axons may be myelinated, or unmyelinated. This is the provision of an insulating layer, called a myelin sheath. In the peripheral nervous system axons are myelinated by glial cells known as Schwann cells. 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.[16]

Nodes of Ranvier

Nodes of Ranvier (also known as myelin sheath gaps) are short unmyelinated segments of a 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.[17] 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–end of tree). At the end of each telodendron is an axon terminal (also called a synaptic bouton, or terminal bouton). Axon terminals contain synaptic vesicles that store the neurotransmitter for release at the 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.

Action potentials

Structure of a typical chemical synapse

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-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.[5]

Example of Waveforms from Extracellular Tetrode Recordings in the Hippocampus from Different Cell Types and Axons
(A) pyramidal cell, interneuron, and short durationwaveform (Axon), overlay of the three average waveforms;
(B) Average and standard error of peak-trough time for pyramidal cells interneurons, and putative axons;
(C) Scatter plot of signal to noise ratios for individual units againstpeak-trough time for axons, pyramidal cells (PYR) and interneurons (INT).

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 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.[18]

In fact, the generation of action potentials in vivo is sequential in nature, and these sequential spikes constitute the 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.[19][20]

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.[21]

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.[22] Studies done on cultured hippocampal neurons suggest that neurons initially produce multiple neurites that are equivalent, yet only one of these neurites is destined to become the axon.[23] It is unclear whether axon specification precedes axon elongation or vice versa,[24] 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.[25] Imposing an external force on a neurite, causing it to elongate, will make it become an axon.[26] Nonetheless, axonal development is achieved through a complex interplay between extracellular signaling, intracellular signaling and cytoskeletal dynamics.

Extracellular signaling

The extracellular signals that propagate through the extracellular matrix surrounding neurons play a prominent role in axonal development.[27] 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.[28][29][30][31] 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.[32]

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.[33]

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.[27]

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.[33] 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.[34]

Growth

Axon two photon
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 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 N-CAM, TAG-1—an axonal glycoprotein[35]—and 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.

Cells called guidepost cells assist in the guidance of neuronal axon growth. These cells are typically other, sometimes immature, neurons.

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.[36]

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.[37] A recent study has also found that macrophages 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.[38]

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)[3] and these differences were thought to relate to the speed that an action potential could travel along the axon – its conductance velocity. 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.

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 fibres (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 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 motor 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.

Motor

Lower motor neurons have two kind of fibers:

Motor fiber types
Type Erlanger-Gasser
Classification
Diameter
(µm)
Myelin Conduction
velocity (m/s)
Associated muscle fibers
α 13-20 Yes 80–120 Extrafusal muscle fibers
β
γ 5-8 Yes 4–24[39][40] Intrafusal muscle fibers

Sensory

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.

Sensory fiber types
Type Erlanger-Gasser
Classification
Diameter
(µm)
Myelin Conduction
velocity (m/s)
Associated sensory receptors Proprioceptors Mechanoceptors Nociceptors and
thermoreceptors
Ia 13-20 Yes 80–120 Primary receptors of muscle spindle (annulospiral ending)
Ib 13-20 Yes 80–120 Golgi tendon organ
II 6-12 Yes 33–75 Secondary receptors of muscle spindle (flower-spray ending).
All cutaneous mechanoreceptors
III 1-5 Thin 3–30 Free nerve endings of touch and pressure
Nociceptors of lateral spinothalamic tract
Cold thermoreceptors
IV C 0.2-1.5 No 0.5-2.0 Nociceptors of anterior spinothalamic tract
Warmth receptors

Autonomic

The autonomic nervous system has two kinds of peripheral fibers:

Fiber types
Type Erlanger-Gasser
Classification
Diameter
(µm)
Myelin[41] Conduction
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

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.[42] 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.[5]

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 leukodystrophies, and also in schizophrenia.[43][44][45]

A 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.[46]

History

German anatomist Otto Friedrich Karl Deiters is generally credited with the discovery of the axon by distinguishing it from the dendrites.[5] 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.[47] 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. 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.[5] Joseph Erlanger and Herbert Gasser earlier developed the classification system for peripheral nerve fibers,[48] based on axonal conduction velocity, myelination, fiber size etc. 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.[49] The giant squid has the 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 Penaeid shrimps[50] and the usual range is between 90 and 200 m/s[51] (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.[52] In many species some of the neurons have axons that emanate from the dendite and not from the cell body, and these are known as axon-carrying dendrites.[1] 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.[52]

See also

References

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External links

Action potential

In physiology, an action potential occurs when the membrane potential of a specific axon location rapidly rises and falls: this depolarisation then causes adjacent locations to similarly depolarise. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, endocrine cells, and in some plant cells.

In neurons, action potentials play a central role in cell-to-cell communication by providing for—or with regard to saltatory conduction, assisting—the propagation of signals along the neuron's axon toward synaptic boutons situated at the ends of an axon; these signals can then connect with other neurons at synapses, or to motor cells or glands. In other types of cells, their main function is to activate intracellular processes. In muscle cells, for example, an action potential is the first step in the chain of events leading to contraction. In beta cells of the pancreas, they provoke release of insulin. Action potentials in neurons are also known as "nerve impulses" or "spikes", and the temporal sequence of action potentials generated by a neuron is called its "spike train". A neuron that emits an action potential, or nerve impulse, is often said to "fire".

Action potentials are generated by special types of voltage-gated ion channels embedded in a cell's plasma membrane. These channels are shut when the membrane potential is near the (negative) resting potential of the cell, but they rapidly begin to open if the membrane potential increases to a precisely defined threshold voltage, depolarising the transmembrane potential. When the channels open, they allow an inward flow of sodium ions, which changes the electrochemical gradient, which in turn produces a further rise in the membrane potential. This then causes more channels to open, producing a greater electric current across the cell membrane and so on. The process proceeds explosively until all of the available ion channels are open, resulting in a large upswing in the membrane potential. The rapid influx of sodium ions causes the polarity of the plasma membrane to reverse, and the ion channels then rapidly inactivate. As the sodium channels close, sodium ions can no longer enter the neuron, and they are then actively transported back out of the plasma membrane. Potassium channels are then activated, and there is an outward current of potassium ions, returning the electrochemical gradient to the resting state. After an action potential has occurred, there is a transient negative shift, called the afterhyperpolarization.

In animal cells, there are two primary types of action potentials. One type is generated by voltage-gated sodium channels, the other by voltage-gated calcium channels. Sodium-based action potentials usually last for under one millisecond, but calcium-based action potentials may last for 100 milliseconds or longer. In some types of neurons, slow calcium spikes provide the driving force for a long burst of rapidly emitted sodium spikes. In cardiac muscle cells, on the other hand, an initial fast sodium spike provides a "primer" to provoke the rapid onset of a calcium spike, which then produces muscle contraction.In the Hodgkin–Huxley membrane capacitance model, the speed of transmission of an action potential was undefined and it was assumed that adjacent areas became depolarised due to released ion interference with neighbouring channels. Measurements of ion diffusion and radii have since shown this not to be possible. Moreover, contradictory measurements of entropy changes and timing disputed the capacitance model as acting alone.

Axon hillock

The axon hillock is a specialized part of the cell body (or soma) of a neuron that connects to the axon. It can be identified using light microscopy from its appearance and location in a neuron and from its sparse distribution of Nissl substance.The axon hillock is the last site in the soma where membrane potentials propagated from synaptic inputs are summated before being transmitted to the axon. For many years, it was believed that the axon hillock was the usual site of initiation of action potentials—the trigger zone. It is now thought that the earliest site of action potential initiation is at the initial segment: just between the peak of the axon hillock and the initial (unmyelinated) segment of the axon. However, the positive point, at which the action potential starts, varies between cells. It can also be altered by hormonal stimulation of the neuron, or by second messenger effects of neurotransmitters.The axon hillock also functions as a tight junction, because it acts as a barrier for lateral diffusion of transmembrane proteins, GPI anchored proteins such as thy1, and lipids embedded in the plasma membrane.

Axon terminal

Axon terminals (also called synaptic boutons or terminal boutons) 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 conducts electrical impulses called action potentials away from the neuron's cell body, or soma, in order to transmit those impulses to other neurons, muscle cells or glands.

Neurons are interconnected in complex arrangements, and use electrochemical signals and neurotransmitter chemicals to transmit impulses from one neuron to the next; axon terminals are separated from neighboring neurons by a small gap called a synapse, across which impulses are sent. The axon terminal, and the neuron from which it comes, is sometimes referred to as the "presynaptic" neuron.

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 neuron from which the dendrites project. Electrical stimulation is transmitted onto dendrites by upstream neurons (usually via their axons) via synapses which are located at various points throughout the dendritic tree. Dendrites play a critical role in integrating these synaptic inputs and in determining the extent to which action potentials are produced by the neuron. Dendritic arborization, also known as dendritic branching, is a multi-step biological process by which neurons form new dendritic trees and branches to create new synapses. The morphology of dendrites such as branch density and grouping patterns are highly correlated to the function of the neuron. Malformation of dendrites is also tightly correlated to impaired nervous system function. Some disorders that are associated with the malformation of dendrites are autism, depression, schizophrenia, Down syndrome and anxiety.

Certain classes of dendrites contain small projections referred to as dendritic spines that increase receptive properties of dendrites to isolate signal specificity. Increased neural activity and the establishment of long-term potentiation at dendritic spines change the size, shape, and conduction. This ability for dendritic growth is thought to play a role in learning and memory formation. There can be as many as 15,000 spines per cell, each of which serves as a postsynaptic process for individual presynaptic axons. Dendritic branching can be extensive and in some cases is sufficient to receive as many as 100,000 inputs to a single neuron.Dendrites are one of two types of protoplasmic protrusions that extrude from the cell body of a neuron, the other type being an axon. Axons can be distinguished from dendrites by several features including shape, length, and function. Dendrites often taper off in shape and are shorter, while axons tend to maintain a constant radius and be relatively long. Typically, axons transmit electrochemical signals and dendrites receive the electrochemical signals, although some types of neurons in certain species lack axons and simply transmit signals via their dendrites. Dendrites provide an enlarged surface area to receive signals from the terminal buttons of other axons, and the axon also commonly divides at its far end into many branches (telodendria) each of which ends in a nerve terminal, allowing a chemical signal to pass simultaneously to many target cells. Typically, when an electrochemical signal stimulates a neuron, it occurs at a dendrite and causes changes in the electrical potential across the neuron's plasma membrane. This change in the membrane potential will passively spread across the dendrite but becomes weaker with distance without an action potential. An action potential propagates the electrical activity along the membrane of the neuron's dendrites to the cell body and then afferently down the length of the axon to the axon terminal, where it triggers the release of neurotransmitters into the synaptic cleft. However, synapses involving dendrites can also be axodendritic, involving an axon signaling to a dendrite, or dendrodendritic, involving signaling between dendrites. An autapse is a synapse in which the axon of one neuron transmits signals to its own dendrites.

There are three main types of neurons; multipolar, bipolar, and unipolar. Multipolar neurons, such as the one shown in the image, are composed of one axon and many dendritic trees. Pyramidal cells are multipolar cortical neurons with pyramid shaped cell bodies and large dendrites called apical dendrites that extend to the surface of the cortex. Bipolar neurons have one axon and one dendritic tree at opposing ends of the cell body. Unipolar neurons have a stalk that extends from the cell body that separates into two branches with one containing the dendrites and the other with the terminal buttons. Unipolar dendrites are used to detect sensory stimuli such as touch or temperature.

John Axon

John Axon GC (4 December 1900 – 9 February 1957) was an English train driver from Stockport (Edgeley Depot) who died while trying to stop a runaway freight train on a 1 in 58 gradient at Chapel-en-le-Frith in Derbyshire after a brake failure. The train consisted of an ex-LMS Stanier Class 8F 2-8-0 No. 48188 hauling 33 wagons and a brake van.

Microsoft Visio

Microsoft Visio ( VIZ-ee-oh) (formerly Microsoft Office Visio) is a diagramming and vector graphics application and is part of the Microsoft Office family. The product was first introduced in 1992, made by the Shapeware Corporation. It was acquired by Microsoft in 2000.

Myelin

Myelin is a lipid-rich (fatty) substance formed in the central nervous system (CNS) by glial cells called oligodendrocytes, and in the peripheral nervous system (PNS) by Schwann cells. Myelin insulates nerve cell axons to increase the speed at which information (encoded as an electrical signal) travels from one nerve cell body to another (as in the CNS) or, for example, from a nerve cell body to a muscle (as in the PNS). The myelinated axon can be likened to an electrical wire (the axon) with insulating material (myelin) around it. However, unlike the plastic covering on an electrical wire, myelin does not form a single long sheath over the entire length of the axon. Rather, each myelin sheath insulates the axon over a single section and, in general, each axon comprises multiple long myelinated sections separated from each other by short gaps called Nodes of Ranvier. Each myelin sheath is formed by the concentric wrapping of an oligodendrocyte or Schwann cell process around the axon.

More precisely, myelin speeds the transmission of electrical impulses called action potentials along myelinated axons by insulating the axon and reducing axonal membrane capacitance. This results in saltatory conduction whereby the action potential "jumps" from one node of Ranvier, over a long myelinated stretch of the axon called the internode, before "recharging" at the next node of Ranvier, and so on, until it reaches the axon terminal. Nodes of Ranvier are the short (~1 micron) unmyelinated regions of the axon between adjacent long (~0.2 mm - >1 mm) myelinated internodes. Once it reaches the axon terminal, this electrical signal provokes the release of a chemical message or neurotransmitter that binds to receptors on the adjacent post-synaptic cell (e.g. nerve cell in the CNS or muscle cell in the PNS) at specialised regions called synapses.

This "insulating" role for myelin is essential for normal motor function (i.e. movement such as walking), sensory function (e.g. hearing, seeing or feeling the sensation of pain) and cognition (e.g. acquiring and recalling knowledge), as demonstrated by the consequences of disorders that affect it, such as the genetically determined leukodystrophies; the acquired inflammatory demyelinating disorder, multiple sclerosis; and the inflammatory demyelinating peripheral neuropathies. Due to its high prevalence, multiple sclerosis, which specifically affects the central nervous system (brain, spinal cord and optic nerve), is the best known disorder of myelin.

Nerve

A nerve is an enclosed, cable-like bundle of nerve fibres called axons, in the peripheral nervous system. A nerve provides a common pathway for the electrochemical nerve impulses called action potentials that are transmitted along each of the axons to peripheral organs or, in the case of sensory nerves, from the periphery back to the central nervous system. Each axon within the nerve is an extension of an individual neuron, along with other supportive cells such as Schwann cells that coat the axons in myelin.

Within a nerve, each axon is surrounded by a layer of connective tissue called the endoneurium. The axons are bundled together into groups called fascicles, and each fascicle is wrapped in a layer of connective tissue called the perineurium. Finally, the entire nerve is wrapped in a layer of connective tissue called the epineurium.

In the central nervous system, the analogous structures are known as tracts.

Nerve injury

Nerve injury is injury to nervous tissue. There is no single classification system that can describe all the many variations of nerve injury. In 1941, Seddon introduced a classification of nerve injuries based on three main types of nerve fiber injury and whether there is continuity of the nerve. Usually, however, (peripheral) nerve injury is classified in five stages, based on the extent of damage to both the nerve and the surrounding connective tissue, since supporting glial cells may be involved. Unlike in the central nervous system, neuroregeneration in the peripheral nervous system is possible. The processes that occur in peripheral regeneration can be divided into the following major events: Wallerian degeneration, axon regeneration/growth, and nerve reinnervation. The events that occur in peripheral regeneration occur with respect to the axis of the nerve injury. The proximal stump refers to the end of the injured neuron that is still attached to the neuron cell body; it is the part that regenerates. The distal stump refers to the end of the injured neuron that is still attached to the end of the axon; it is the part of the neuron that will degenerate but that remains in the area toward which the regenerating axon grows. The study of peripheral nerve injury began during the American Civil War and has greatly expanded to the point of using growth-promoting molecules.

Nervous tissue

Nervous tissue, also called neural tissue or nerve tissue, is the main tissue component of the nervous system. The nervous system regulates and controls bodily functions and activity and consists of two parts: the central nervous system (CNS) comprising the brain and spinal cord, and the peripheral nervous system (PNS) comprising the branching peripheral nerves. It is composed of neurons, or nerve cells, which receive and transmit impulses, and neuroglia, also known as glial cells or glia, which assist the propagation of the nerve impulse as well as provide nutrients to the neurons.

Nervous tissue is made up of different types of nerve cells, all of which have an axon. An axon is the long stem-like part of the cell that sends action potential signals to the next cell. Bundles of axons make up the nerves in the PNS and tracts in the CNS.

Functions of the nervous system are sensory input, integration, control of muscles and glands, homeostasis, and mental activity.

Neuron

A neuron, also known as a neurone (British spelling) and nerve cell, is an electrically excitable cell that communicates with other cells via specialized connections called synapses. All animals except sponges and placozoans have neurons, but other multicellular organisms such as plants do not. A neuron is the main component of nervous tissue.

Neurons fall into types. Sensory neurons respond to stimulus such as touch, sound, or light that affect the cells of the sensory organs and sends signals to the spinal cord or brain. Motor neurons receive signals from the brain and spinal cord to control everything from muscle contractions to glandular output. Interneurons connect neurons to other neurons within the same region of the brain or spinal cord in neural circuits.

A typical neuron consists of a cell body (soma), dendrites, and a single axon. The soma is usually compact. The axon and dendrites are filaments that extrude from it. Dendrites typically branch profusely, getting thinner with each branching, and extending a few hundred micrometers from the soma. The axon leaves the soma at a swelling called the axon hillock, and travels for as far as 1 meter in humans or more in other species. It also branches, but usually maintains a constant diameter. Neurons can lack dendrites, or have no axon. An en passant bouton is a type of terminal located along the length of the axon. The term neurite is used to describe either a dendrite or an axon, particularly in its undifferentiated stage.

Most neurons receive signals via the dendrites and soma and send out signals down the axon. At the majority of synapses, signals cross from the axon of one neuron to a dendrite of another. However, synapses can connect an axon to another axon or a dendrite to another dendrite.

The signaling process is partly electrical and partly chemical. Neurons are electrically excitable, due to maintenance of voltage gradients across their membranes. If the voltage changes by a large enough amount over a short interval, the neuron generates an all-or-nothing electrochemical pulse called an action potential. This potential travels rapidly along the axon, and activates synaptic connections as it reaches them. Synaptic signals may be excitatory or inhibitory, increasing or reducing the net voltage that reaches the soma.

In most cases, neurons are generated by neural stem cells during brain development and childhood.Neurogenesis largely ceases during adulthood in most areas of the brain. However, strong evidence supports generation of substantial numbers of new neurons in the hippocampus and olfactory bulb.

Neurotransmission

Neurotransmission (Latin: transmissio "passage, crossing" from transmittere "send, let through"), is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron), and bind to and react with the receptors on the dendrites of another neuron (the postsynaptic neuron). A similar process occurs in retrograde neurotransmission, where the dendrites of the postsynaptic neuron release retrograde neurotransmitters (e.g., endocannabinoids) that signal through receptors that are located on the axon terminal of the presynaptic neuron, mainly at GABAergic and glutamatergic synapses.Neurotransmission relies upon: the availability of the neurotransmitter; the release of the neurotransmitter; the connection made between the postsynaptic receptor by the neurotransmitter; activity from the postsynaptic cell; and the subsequent removal or deactivation of the neurotransmitter.

In response to a threshold action potential or graded electrical potential, a neurotransmitter is released at the presynaptic terminal. The released neurotransmitter may then move across the synapse to be detected by and bind with receptors in the postsynaptic neuron. Binding of neurotransmitters may influence the postsynaptic neuron in either an inhibitory or excitatory way. The binding of neurotransmitters to receptors in the postsynaptic neuron can trigger either short term changes, such as changes in the membrane potential called postsynaptic potentials, or longer term changes by the activation of signaling cascades.

Neurons form complex biological neural networks through which nerve impulses (action potentials) travel. Neurons do not touch each other (except in the case of an electrical synapse through a gap junction); instead, neurons interact at close contact points called synapses. A neuron transports its information by way of an action potential. When the nerve impulse arrives at the synapse, it may cause the release of neurotransmitters, which influence another (postsynaptic) neuron. The postsynaptic neuron may receive inputs from many additional neurons, both excitatory and inhibitory. The excitatory and inhibitory influences are summed, and if the net effect is inhibitory, the neuron will be less likely to "fire" (i.e., generate an action potential), and if the net effect is excitatory, the neuron will be more likely to fire. How likely a neuron is to fire depends on how far its membrane potential is from the threshold potential, the voltage at which an action potential is triggered because enough voltage-dependent sodium channels are activated so that the net inward sodium current exceeds all outward currents. Excitatory inputs bring a neuron closer to threshold, while inhibitory inputs bring the neuron farther from threshold. An action potential is an "all-or-none" event; neurons whose membranes have not reached threshold will not fire, while those that do must fire. Once the action potential is initiated (traditionally at the axon hillock), it will propagate along the axon, leading to release of neurotransmitters at the synaptic bouton to pass along information to yet another adjacent neuron.

Nigrostriatal pathway

The nigrostriatal pathway or the nigrostriatal bundle (NSB), is a dopaminergic pathway that connects the substantia nigra pars compacta (SNc) with the dorsal striatum (i.e., the caudate nucleus and putamen). It is one of the four major dopamine pathways in the brain, and is particularly involved in the production of movement, as part of a system called the basal ganglia motor loop. Dopaminergic neurons of this pathway synapse onto GABAergic neurons.Loss of dopamine neurons in the SNc is one of the main pathological features of Parkinson's disease, leading to a marked reduction in dopamine function in this pathway. Depletion of neurons in this pathway lead to the symptomatic motor deficits of Parkinson's disease including tremors, rigidity, and postural imbalance.

Nociception

Nociception (also nocioception or nociperception, from Latin nocere 'to harm or hurt') is the sensory nervous system's response to certain harmful or potentially harmful stimuli. In nociception, intense chemical (e.g., chili powder in the eyes), mechanical (e.g., cutting, crushing), or thermal (heat and cold) stimulation of sensory nerve cells called nociceptors produces a signal that travels along a chain of nerve fibers via the spinal cord to the brain. Nociception triggers a variety of physiological and behavioral responses and usually results in a subjective experience of pain in sentient beings.

Node of Ranvier

Nodes of Ranvier ( RAHN-vee-AY, -⁠ay), 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 in the exchange of ions required to regenerate the action potential. Nerve conduction in myelinated axons is referred to as saltatory conduction (from the Latin saltare "to hop or to leap") due to the manner in which the action potential seems to "jump" from one node to the next along the axon. This results in faster conduction of the action potential.

Olivocerebellar tract

The olivocerebellar tract, also known as olivocerebellar fibers, are neural fibers which originate at the olivary nucleus and pass out through the hilum and decussate with those from the opposite olive in the raphe nucleus, then as internal arcuate fibers they pass partly through and partly around the opposite olive and enter the inferior peduncle to be distributed to the cerebellar hemisphere of the opposite side from which they arise.

They terminate directly on Purkinje cells as the climbing fiber input system.

Soma (biology)

The soma (pl. somata or somas), perikaryon (pl. perikarya), neurocyton, or cell body is the bulbous, non-process portion of a neuron or other brain cell type, containing the cell nucleus. The word 'soma' comes from the Greek 'σῶμα', meaning 'body'. Although it is often used to refer to neurons, it can also refer to other cell types as well, including astrocytes, oligodendrocytes, and microglia. There are many different specialized types of neurons, and their sizes vary from as small as about 5 micrometres to over 10 millimetre for some of the smallest and largest neurons of invertebrates, respectively.

The soma of a neuron (i.e., the main part of the neuron in which the dendrites branch off of) contains many organelles, including granules called Nissl granules, which are composed largely of rough endoplasmic reticulum and free polyribosomes. The cell nucleus is a key feature of the soma. The nucleus is the source of most of the RNA that is produced in neurons. In general, most proteins are produced from mRNAs that do not travel far from the cell nucleus. This creates a challenge for supplying new proteins to axon endings that can be a meter or more away from the soma. Axons contain microtubule-associated motor proteins that transport protein-containing vesicles between the soma and the synapses at the axon terminals. Such transport of molecules towards and away from the soma maintains critical cell functions.

The axon hillock is a specialized domain of the neuronal cell body from which the axon originates. A high amount of protein synthesis occurs in this region, as it contains a large number of Nissl granules (which are ribosomes wrapped in RER) and polyribosomes. Within the axon hillock, materials are sorted as either items that will enter the axon (like the components of the cytoskeletal architecture of the axon, mitochondria, etc.) or will remain in the soma. In addition, the axon hillock also has a specialized plasma membrane that contains large numbers of voltage-gated ion channels, since this is most often the site of action potential initiation.The survival of some sensory neurons depends on axon terminals making contact with sources of survival factors that prevent apoptosis. The survival factors are neurotrophic factors, including molecules such as nerve growth factor (NGF). NGF interacts with receptors at axon terminals, and this produces a signal that must be transported up the length of the axon to the nucleus. A current theory of how such survival signals are sent from axon endings to the soma includes the idea that NGF receptors are endocytosed from the surface of axon tips and that such endocytotic vesicles are transported up the axon.

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,[page needed] but this discovery was forgotten until English zoologist and neurophysiologist J. Z. Young demonstrated the axon's function in the 1930s while working in the Stazione Zoologica in Naples, the Marine Biological Association in Plymouth and the Marine Biological Laboratory in Woods Hole. Squids use this system primarily for making brief but very fast movements through the water.

Between the tentacles of a squid is a siphon through which water can be rapidly expelled by the fast contractions of the body wall muscles of the animal. This contraction is initiated by action potentials in the giant axon. Action potentials travel faster in a larger axon than a smaller one,[page needed] and squid have evolved the giant axon to improve the speed of their escape response. The increased diameter of the squid axon decreases the internal resistance of the axon, as resistance is inversely proportional to the cross sectional area of the object. This increases the space constant (), leading to faster local depolarization and a faster action potential ().[page needed]

In their Nobel Prize-winning work uncovering ionic mechanism of action potentials, Alan Hodgkin and Andrew Huxley performed experiments on the squid giant axon, using the longfin inshore squid as the model organism. The prize was shared with John Eccles. The large diameter of the axon provided a great experimental advantage for Hodgkin and Huxley as it allowed them to insert voltage clamp electrodes inside the lumen of the axon.

While the squid axon is very large in diameter it is unmyelinated which decreases the conduction velocity substantially. The conduction velocity of a typical 0.5 mm squid axon is about 25 m/s. During a typical action potential in the cuttlefish Sepia giant axon, an influx of 3.7 pmol/cm2 (picomoles per centimeter2) of sodium is offset by a subsequent efflux of 4.3 pmol/cm2 of potassium.

Synapse

In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell.

Santiago Ramón y Cajal proposed that neurons are not continuous throughout the body, yet still communicate with each other, an idea known as the neuron doctrine. The word "synapse" – from the Greek synapsis (συνάψις), meaning "conjunction", in turn from συνάπτεὶν (συν ("together") and ἅπτειν ("to fasten")) – was introduced in 1897 by the English neurophysiologist Charles Sherrington in Michael Foster's Textbook of Physiology. Sherrington struggled to find a good term that emphasized a union between two separate elements, and the actual term "synapse" was suggested by the English classical scholar Arthur Woollgar Verrall, a friend of Foster. Some authors generalize the concept of the synapse to include the communication from a neuron to any other cell type, such as to a motor cell, although such non-neuronal contacts may be referred to as junctions (a historically older term).

Synapses are essential to neuronal function: neurons are cells that are specialized to pass signals to individual target cells, and synapses are the means by which they do so. At a synapse, the plasma membrane of the signal-passing neuron (the presynaptic neuron) comes into close apposition with the membrane of the target (postsynaptic) cell. Both the presynaptic and postsynaptic sites contain extensive arrays of a molecular machinery that link the two membranes together and carry out the signaling process. In many synapses, the presynaptic part is located on an axon and the postsynaptic part is located on a dendrite or soma. Astrocytes also exchange information with the synaptic neurons, responding to synaptic activity and, in turn, regulating neurotransmission. Synapses (at least chemical synapses) are stabilized in position by synaptic adhesion molecules (SAMs) projecting from both the pre- and post-synaptic neuron and sticking together where they overlap; SAMs may also assist in the generation and functioning of synapses.

CNS
PNS
Neurons/
nerve fibers
Termination

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