neuron

Neuron: neuron (Nerve Cell)
Drawing by Santiago Ramón y Cajal of neurons in the pigeon cerebellum. (A) Denotes Purkinje cells, an example of a bipolar neuron. (B) Denotes granule cells which are multipolar.
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A neuron (pronounced /ˈnjʊərɒn/ N(Y)OOR-on, also known as a neurone or nerve cell) is an excitable cell in the nervous system that processes and transmits information by electrochemical signalling. Neurons are the core components of the brain, the vertebrate spinal cord, the invertebrate ventral nerve cord, and the peripheral nerves. A number of specialized types of neurons exist: sensory neurons respond to touch, sound, light and numerous other stimuli affecting cells of the sensory organs that then send signals to the spinal cord and brain. Motor neurons receive signals from the brain and spinal cord and cause muscle contractions and affect glands. Interneurons connect neurons to other neurons within the same region of the brain or spinal cord. Neurons respond to stimuli, and communicate the presence of stimuli to the central nervous system, which processes that information and sends responses to other parts of the body for action. Neurons do not go through mitosis, and usually cannot be replaced after being destroyed, although astrocytes have been observed to turn into neurons as they are sometimes pluripotent.

Overview

Structure of a typical neuron

Neuron
Dendrite Soma Axon Nucleus Node of Ranvier Axon Terminal Schwann cell Myelin sheath

The complexity and diversity in nervous systems is dependent on the interconnections between neurons, which rely on a limited number of different signals transmitted within the neurons to other neurons or to muscles and glands. The signals are produced and propagated by chemical ions that produce an electrical charge that moves along the neuron.

Neurons exist in a number of different shapes and sizes and can be classified by their morphology and function. The anatomist Camillo Golgi grouped neurons into two types; type I with long axons used to move signals over long distances and type II without axons. Type I cells can be further divided by where the cell body or soma is located. The basic morphology of type I neurons, represented by spinal motor neurons, consists of a cell body called the soma and a long thin axon which is covered by the myelin sheath. Around the cell body is a branching dendritic tree that receives signals from other neurons. The end of the axon has branching terminals (axon terminal) that release neurotransmitters into a gap called the synaptic cleft between the terminals and the dendrites of the next neuron. The anatomy and the properties of the surface membrane determine the behavior of a neuron. The surface membrane is not uniform over the entire length of a neuron, but is modified in specific areas: some regions secrete transmitter substances while other areas respond to the transmitter. Other areas of the neuron membrane have passive electrical properties that affect capacitance and resistance. Within the neuron membrane there are gated ion channels that vary in type, including fast response sodium channels that are voltage-gated and are used to send rapid signals.

Neurons communicate by chemical and electrical synapses in a process known as synaptic transmission. The fundamental process that triggers synaptic transmission is the action potential, a propagating electrical signal that is generated by exploiting the electrically excitable membrane of the neuron. This is also known as a wave of depolarization.

Fully differentiated neurons are permanently amitotic;^[1] however, recent research shows that additional neurons throughout the brain can originate from neural stem cells found throughout the brain but in particularly high concentrations in the subventricular zone and subgranular zone through the process of neurogenesis.^[2][3][4][5]

History

The neuron's place as the primary functional unit of the nervous system was first recognized in the early 20th century through the work of the Spanish anatomist Santiago Ramón y Cajal.^[6] Cajal proposed that neurons were discrete cells that communicated with each other via specialized junctions, or spaces, between cells.^[6] This became known as the neuron doctrine, one of the central tenets of modern neuroscience.^[6] To observe the structure of individual neurons, Cajal used a silver staining method developed by his rival, Camillo Golgi.^[6] The Golgi stain is an extremely useful method for neuroanatomical investigations because, for reasons unknown, it stains a very small percentage of cells in a tissue, so one is able to see the complete micro structure of individual neurons without much overlap from other cells in the densely packed brain.^[7]

Anatomy and histology

Diagram of a typical myelinated vertebrate motoneuron.

Neurons are highly specialized for the processing and transmission of cellular signals. Given the diversity of functions performed by neurons in different parts of the nervous system, there is, as expected, a wide variety in the shape, size, and electrochemical properties of neurons. For instance, the soma of a neuron can vary from 4 to 100 micrometers in diameter.^[8]

• The soma is the central part of the neuron. It contains the nucleus of the cell, and therefore is where most protein synthesis occurs. The nucleus ranges from 3 to 18 micrometers in diameter.^[9]

• The dendrites of a neuron are cellular extensions with many branches, and metaphorically this overall shape and structure is referred to as a dendritic tree. This is where the majority of input to the neuron occurs. Information outflow (i.e. from dendrites to other neurons) can also occur, but not across chemical synapses; there, the back flow of a nerve impulse is inhibited by the fact that an axon does not possess chemoreceptors and dendrites cannot secrete neurotransmitter chemicals. This unidirectionality of a chemical synapse explains why nerve impulses are conducted only in one direction.

• The axon is a finer, cable-like projection which can extend tens, hundreds, or even tens of thousands of times the diameter of the soma in length. The axon carries nerve signals away from the soma (and also carries some types of information back to it). Many neurons have only one axon, but this axon may - and usually will - undergo extensive branching, enabling communication with many target cells. The part of the axon where it emerges from the soma is called the axon hillock. Besides being an anatomical structure, the axon hillock is also the part of the neuron that has the greatest density of voltage-dependent sodium channels. This makes it the most easily-excited part of the neuron and the spike initiation zone for the axon: in neurological terms it has the most negative action potential threshold. While the axon and axon hillock are generally involved in information outflow, this region can also receive input from other neurons.

• The axon terminal contains synapses, specialized structures where neurotransmitter chemicals are released in order to communicate with target neurons.

Although the canonical view of the neuron attributes dedicated functions to its various anatomical components, dendrites and axons often act in ways contrary to their so-called main function.

Axons and dendrites in the central nervous system are typically only about one micrometer thick, while some in the peripheral nervous system are much thicker. The soma is usually about 10–25 micrometers in diameter and often is not much larger than the cell nucleus it contains. The longest axon of a human motoneuron can be over a meter long, reaching from the base of the spine to the toes. Sensory neurons have axons that run from the toes to the dorsal columns, over 1.5 meters in adults. Giraffes have single axons several meters in length running along the entire length of their necks. Much of what is known about axonal function comes from studying the squid giant axon, an ideal experimental preparation because of its relatively immense size (0.5–1 millimeters thick, several centimeters long).

Classes

Image of pyramidal neurons in mouse cerebral cortex expressing green fluorescent protein. The red staining indicates GABAergic interneurons. Source PLoS Biology [1]

SMI32-stained pyramidal neurons in cerebral cortex.

Structural classification

Polarity

Most neurons can be anatomically characterized as:

• Unipolar or pseudounipolar: dendrite and axon emerging from same process.
• Bipolar: axon and single dendrite on opposite ends of the soma.
• Multipolar: more than two dendrites:
  • Golgi I: neurons with long-projecting axonal processes; examples are pyramidal cells, Purkinje cells, and anterior horn cells.
  • Golgi II: neurons whose axonal process projects locally; the best example is the granule cell.

Other

Furthermore, some unique neuronal types can be identified according to their location in the nervous system and distinct shape. Some examples are:

• Basket cells, neurons with dilated and knotty dendrites in the cerebellum.
• Betz cells, large motor neurons.
• Medium spiny neurons, most neurons in the corpus striatum.
• Purkinje cells, huge neurons in the cerebellum, a type of Golgi I multipolar neuron.
• Pyramidal cells, neurons with triangular soma, a type of Golgi I.
• Renshaw cells, neurons with both ends linked to alpha motor neurons.
• Granule cells, a type of Golgi II neuron.
• anterior horn cells, motoneurons located in the spinal cord.

Functional classification

Direction

• Afferent neurons convey information from tissues and organs into the central nervous system and are sometimes also called sensory neurons.
• Efferent neurons transmit signals from the central nervous system to the effector cells and are sometimes called motor neurons.
• Interneurons connect neurons within specific regions of the central nervous system.

Afferent and efferent can also refer generally to neurons which, respectively, bring information to or send information from the brain region.

Action on other neurons

A neuron affects other neurons by releasing a neurotransmitter that binds to chemical receptors. The effect upon the target neuron is determined not by the source neuron or by the neurotransmitter, but by the type of receptor that is activated. A neurotransmitter can be thought of as a key, and a receptor as a lock: the same type of key can here be used to open many different types of locks. Receptors can be classified broadly as excitatory (causing an increase in firing rate), inhibitory (causing a decrease in firing rate), or modulatory (causing long-lasting effects not directly related to firing rate).

In fact, however, the two most common neurotransmitters in the brain, glutamate and GABA, have actions that are largely consistent. Glutamate acts on several different types of receptors, but most of them have effects that are excitatory. Similarly GABA acts on several different types of receptors, but all of them have effects (in adult animals, at least) that are inhibitory. Because of this consistency, it is common for neuroscientists to simplify the terminology by referring to cells that release glutamate as "excitatory neurons," and cells that release GABA as "inhibitory neurons." Since well over 90% of the neurons in the brain release either glutamate or GABA, these labels encompass the great majority of neurons. There are also other types of neurons that have consistent effects on their targets, for example "excitatory" motor neurons in the spinal cord that release acetylcholine, and "inhibitory" spinal neurons that release glycine.

The distinction between excitatory and inhibitory neurotransmitters is not absolute, however. Rather, it depends on the class of chemical receptors present on the target neuron. In principle, a single neuron, releasing a single neurotransmitter, can have excitatory effects on some targets, inhibitory effects on others, and modulatory effects on other still. For example, photoreceptors in the retina constantly release the neurotransmitter glutamate in the absence of light. So-called OFF bipolar cells are, like most neurons, excited by the released glutamate. However, neighboring target neurons called ON bipolar cells are instead inhibited by glutamate, because they lack the typical ionotropic glutamate receptors and instead express a class of inhibitory metabotropic glutamate receptors.^[10] When light is present, the photoreceptors cease releasing glutamate, which relieves the ON bipolar cells from inhibition, activating them; this simultaneously removes the excitation from the OFF bipolar cells, silencing them.

Discharge patterns

Neurons can be classified according to their electrophysiological characteristics:

• Tonic or regular spiking. Some neurons are typically constantly (or tonically) active. Example: interneurons in neurostriatum.
• Phasic or bursting. Neurons that fire in bursts are called phasic.
• Fast spiking. Some neurons are notable for their fast firing rates, for example some types of cortical inhibitory interneurons, cells in globus pallidus, retinal ganglion cells^[11][12].
• Thin-spike. Action potentials of some neurons are more narrow compared to the others. For example, interneurons in prefrontal cortex are thin-spike neurons.

Classification by neurotransmitter production

This section requires expansion.

Neurons differ in the type of neurotransmitter they manufacture. Some examples are

• cholinergic neurons - acetylcholine
• GABAergic neurons - gamma aminobutyric acid
• glutamatergic neurons - glutamate
• dopaminergic neurons - dopamine
• serotonergic neurons - serotonin

Connectivity

Neurons communicate with one another via synapses, where the axon terminal or en passant boutons (terminals located along the length of the axon) of one cell impinges upon another neuron's dendrite, soma or, less commonly, axon. Neurons such as Purkinje cells in the cerebellum can have over 1000 dendritic branches, making connections with tens of thousands of other cells; other neurons, such as the magnocellular neurons of the supraoptic nucleus, have only one or two dendrites, each of which receives thousands of synapses. Synapses can be excitatory or inhibitory and will either increase or decrease activity in the target neuron. Some neurons also communicate via electrical synapses, which are direct, electrically-conductive junctions between cells.

In a chemical synapse, the process of synaptic transmission is as follows: when an action potential reaches the axon terminal, it opens voltage-gated calcium channels, allowing calcium ions to enter the terminal. Calcium causes synaptic vesicles filled with neurotransmitter molecules to fuse with the membrane, releasing their contents into the synaptic cleft. The neurotransmitters diffuse across the synaptic cleft and activate receptors on the postsynaptic neuron.

The human brain has a huge number of synapses. Each of the 10¹¹ (one hundred billion) neurons has on average 7,000 synaptic connections to other neurons. It has been estimated that the brain of a three-year-old child has about 10¹⁵ synapses (1 quadrillion). This number declines with age, stabilizing by adulthood. Estimates vary for an adult, ranging from 10¹⁴ to 5 x 10¹⁴ synapses (100 to 500 trillion).^[13]

Mechanisms for propagating action potentials

A signal propagating down an axon to the cell body and dendrites of the next cell.

In 1937, John Zachary Young suggested that the squid giant axon could be used to study neuronal electrical properties.^[14] Being larger than but similar in nature to human neurons, squid cells were easier to study. By inserting electrodes into the giant squid axons, accurate measurements were made of the membrane potential.

The cell membrane of the axon and soma contain voltage-gated ion channels which allow the neuron to generate and propagate an electrical signal (an action potential). These signals are generated and propagated by charge-carrying ions including sodium (Na⁺), potassium (K⁺), chloride (Cl^-), and calcium (Ca²⁺).

There are several stimuli that can activate a neuron leading to electrical activity, including pressure, stretch, chemical transmitters, and changes of the electric potential across the cell membrane.^[15] Stimuli cause specific ion-channels within the cell membrane to open, leading to a flow of ions through the cell membrane, changing the membrane potential.

Thin neurons and axons require less metabolic expense to produce and carry action potentials, but thicker axons convey impulses more rapidly. To minimize metabolic expense while maintaining rapid conduction, many neurons have insulating sheaths of myelin around their axons. The sheaths are formed by glial cells: oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. The sheath enables action potentials to travel faster than in unmyelinated axons of the same diameter, whilst using less energy. The myelin sheath in peripheral nerves normally runs along the axon in sections about 1 mm long, punctuated by unsheathed nodes of Ranvier which contain a high density of voltage-gated ion channels. Multiple sclerosis is a neurological disorder that results from demyelination of axons in the central nervous system.

Some neurons do not generate action potentials, but instead generate a graded electrical signal, which in turn causes graded neurotransmitter release. Such nonspiking neurons tend to be sensory neurons or interneurons, because they cannot carry signals long distances.

All-or-none principle

The conduction of nerve impulses is an example of an all-or-none response. In other words, if a neuron responds at all, then it must respond completely. The greater the intensity of stimulation does not produce a stronger signal but can produce more impulses per second. There are different types of receptor response to stimulus, slowly adapting or tonic receptors respond to steady stimulus and produce a steady rate of firing. These tonic receptors most often respond to increased intensity of stimulus by increasing their firing frequency, usually as a power function of stimulus plotted against impulses per second. This can be likened to an intrinsic property of light where to get greater intensity of a specific frequency (color) there has to be more photons, as the photons can't become "stronger" for a specific frequency.

There are a number of other receptor types that are called quickly adapting or phasic receptors, where firing decreases or stops with steady stimulus, examples include; skin when touched by an object causes the neurons to fire, but if the object maintains even pressure against the skin the neurons stop firing. The neurons of the skin and muscles that are responsive to pressure and vibration have filtering accessory structures that aid their function. The pacinian corpuscle is one such structure, it has concentric layers like an onion which form around the axon terminal. When pressure is applied and the corpuscle is deformed, mechanical stimulus is transferred to the axon, which fires. If the pressure is steady there is no more stimulus, thus typically these neurons respond with a transient depolarization during the initial deformation and again when the pressure is removed which cause the corpuscle to change shape again. Other types of adaptation are important in extending the function of a number of other neurons.^[16]

Histology and internal structure

Golgi-stained neurons in human hippocampal tissue.

Nerve cell bodies stained with basophilic dyes show numerous microscopic clumps of Nissl substance (named after German psychiatrist and neuropathologist Franz Nissl, 1860–1919), which consists of rough endoplasmic reticulum and associated ribosomal RNA. The prominence of the Nissl substance can be explained by the fact that nerve cells are metabolically very active, and hence are involved in large amounts of protein synthesis.

The cell body of a neuron is supported by a complex meshwork of structural proteins called neurofilaments, which are assembled into larger neurofibrils. Some neurons also contain pigment granules, such as neuromelanin (a brownish-black pigment, byproduct of synthesis of catecholamines) and lipofuscin (yellowish-brown pigment that accumulates with age).

There are different internal structural characteristics between axons and dendrites. Axons typically almost never contain ribosomes, except some in the initial segment. Dendrites contain granular endoplasmic reticulum or ribosomes, with diminishing amounts with distance from the cell body.

The neuron doctrine

The neuron doctrine is the now fundamental idea that neurons are the basic structural and functional units of the nervous system. The theory was put forward by Santiago Ramón y Cajal in the late 19th century. It held that neurons are discrete cells (not connected in a meshwork), acting as metabolically distinct units.

As with all doctrines, there are some exceptions. For example glial cells may also play a role in information processing.^[17] Also, electrical synapses are more common than previously thought,^[18] meaning that there are direct, cytoplasmic connections between neurons. In fact, there are examples of neurons forming even tighter coupling; the squid giant axon arises from the fusion of multiple neurons that retain individual cell bodies and the crayfish giant axon consists of a series of neurons with high conductance septate junctions^{[citation needed]}.

Cajal also postulated the Law of Dynamic Polarization, which states that a neuron receives signals at its dendrites and cell body and transmits them, as action potentials, along the axon in one direction: away from the cell body.^[19] The Law of Dynamic Polarization has important exceptions; dendrites can serve as synaptic output sites of neurons^[20] and axons can receive synaptic inputs^{[citation needed]}.

Neurons in the brain

The number of neurons in the brain varies dramatically from species to species.^[21] One estimate puts the human brain at about 100 billion (10¹¹) neurons and 100 trillion (10¹⁴) synapses.^[21] Another estimate is 86 billion neurons of which 16.3 are in the cerebral cortex and 69 in the cerebellum.^[22] By contrast, the nematode worm Caenorhabditis elegans has just 302 neurons making it an ideal experimental subject as scientists have been able to map all of the organism's neurons. By contrast, the fruit fly Drosophila melanogaster has around 100,000 neurons and exhibits many complex behaviors. Many properties of neurons, from the type of neurotransmitters used to ion channel composition, are maintained across species, allowing scientists to study processes occurring in more complex organisms in much simpler experimental systems.

Neurological diseases

Alzheimer's disease (AD), also known simply as Alzheimer's, is a neurodegenerative disease characterized by progressive cognitive deterioration together with declining activities of daily living and neuropsychiatric symptoms or behavioral changes. The most striking early symptom is loss of short-term memory (amnesia), which usually manifests as minor forgetfulness that becomes steadily more pronounced with illness progression, with relative preservation of older memories. As the disorder progresses, cognitive (intellectual) impairment extends to the domains of language (aphasia), skilled movements (apraxia), recognition (agnosia), and functions such as decision-making and planning get impaired.

Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the central nervous system that often impairs the sufferer's motor skills and speech. Parkinson's disease belongs to a group of conditions called movement disorders. It is characterized by muscle rigidity, tremor, a slowing of physical movement (bradykinesia), and in extreme cases, a loss of physical movement (akinesia). The primary symptoms are the results of decreased stimulation of the motor cortex by the basal ganglia, normally caused by the insufficient formation and action of dopamine, which is produced in the dopaminergic neurons of the brain. Secondary symptoms may include high level cognitive dysfunction and subtle language problems. PD is both chronic and progressive.

Myasthenia Gravis is a neuromuscular disease leading to fluctuating muscle weakness and fatigability. Weakness is typically caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction, inhibiting the stimulative effect of the neurotransmitter acetylcholine. Myasthenia is treated with immunosuppressants, cholinesterase inhibitors and, in selected cases, thymectomy.

Demyelination

Demyelination is the act of demyelinating, or the loss of the myelin sheath insulating the nerves. When myelin degrades, conduction of signals along the nerve can be impaired or lost, and the nerve eventually withers. This leads to certain neurodegenerative disorders like multiple sclerosis, chronic inflammatory demyelinating polyneuropathy.

Axonal degeneration

Although most injury responses include a calcium influx signaling to promote resealing of severed parts, axonal injuries initially lead to acute axonal degeneration (AAD), which is rapid separation of the proximal and distal ends within 30 minutes of injury. Degeneration follows with swelling of the axolemma, and eventually leads to bead like formation. Granular disintegration of the axonal cytoskeleton and inner organelles occurs after axolemma degradation. Early changes include accumulation of mitochondria in the paranodal regions at the site of injury. Endoplasmic reticulum degrades and mitochondria swell up and eventually disintegrate. The disintegration is dependent on Ubiquitin and Calpain proteases (caused by influx of calcium ion), suggesting that axonal degeneration is an active process. Thus the axon undergoes complete fragmentation. The process takes about roughly 24 hrs in the PNS, and longer in the CNS. The signaling pathways leading to axolemma degeneration are currently unknown.

Nerve regeneration

Although neurons do not divide or replicate in most parts of the adult vertebrate brain, it is often possible for axons to regrow if they are severed. This can take a long time: after a nerve injury to the human arm, for example, it may take months for feeling to return to the hands and fingers.^{[citation needed]}

References

Sources

• Kandel E.R., Schwartz, J.H., Jessell, T.M. 2000. Principles of Neural Science, 4th ed., McGraw-Hill, New York.
• Bullock, T.H., Bennett, M.V.L., Johnston, D., Josephson, R., Marder, E., Fields R.D. 2005. The Neuron Doctrine, Redux, Science, V.310, p. 791-793.
• Ramón y Cajal, S. 1933 Histology, 10th ed., Wood, Baltimore.
• Roberts A., Bush B.M.H. 1981. Neurones Without Impulses. Cambridge University Press, Cambridge.
• Peters, A., Palay, S.L., Webster, H, D., 1991 The Fine Structure of the Nervous System, 3rd ed., Oxford, New York

External links

• NeuronBankan online neuromics tool for cataloging neuronal types and synaptic connectivity.
• High Resolution Neuroanatomical Images of Primate and Non-Primate Brains.
• The Department of Neuroscience at Wikiversity, which presently offers two courses: Fundamentals of Neuroscience and Comparative Neuroscience.
• NIF Search - Renshaw Cell via the Neuroscience Information Framework
• Cell Centered Database - Neuron

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