Anatomy of a multipolar neuron
|Anatomical terms of neuroanatomy|
A neuron, also known as a neurone (British spelling) and nerve cell, is an electrically excitable cell that receives, processes, and transmits information through electrical and chemical signals. These signals between neurons occur via specialized connections called synapses. Neurons can connect to each other to form neural circuits. Neurons are the primary components of the central nervous system, which includes the brain and spinal cord, and of the peripheral nervous system, which comprises the autonomic nervous system and the somatic nervous system.
There are many types of specialized neurons. Sensory neurons respond to one particular type of stimulus such as touch, sound, or light and all other stimuli affecting the cells of the sensory organs, and converts it into an electrical signal via transduction, which is then sent 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 networks.
A typical neuron consists of a cell body (soma), dendrites, and an axon. The term neurite is used to describe either a dendrite or an axon, particularly in its undifferentiated stage. Dendrites are thin structures that arise from the cell body, often extending for hundreds of micrometers and branching multiple times, giving rise to a complex "dendritic tree". An axon (also called a nerve fiber) is a special cellular extension (process) that arises from the cell body at a site called the axon hillock and travels for a distance, as far as 1 meter in humans or even more in other species. Most neurons receive signals via the dendrites and send out signals down the axon. Numerous axons are often bundled into fascicles that make up the nerves in the peripheral nervous system (like strands of wire make up cables). Bundles of axons in the central nervous system are called tracts. The cell body of a neuron frequently gives rise to multiple dendrites, but never to more than one axon, although the axon may branch hundreds of times before it terminates. At the majority of synapses, signals are sent from the axon of one neuron to a dendrite of another. There are, however, many exceptions to these rules: for example, neurons can lack dendrites, or have no axon, and synapses can connect an axon to another axon or a dendrite to another dendrite.
All neurons are electrically excitable, due to maintenance of voltage gradients across their membranes by means of metabolically driven ion pumps, which combine with ion channels embedded in the membrane to generate intracellular-versus-extracellular concentration differences of ions such as sodium, potassium, chloride, and calcium. Changes in the cross-membrane voltage can alter the function of voltage-dependent ion channels. If the voltage changes by a large enough amount, an all-or-none electrochemical pulse called an action potential is generated and this change in cross-membrane potential travels rapidly along the cell's axon, and activates synaptic connections with other cells when it arrives.
In most cases, neurons are generated by special types of stem cells during brain development and childhood. Neurons in the adult brain generally do not undergo cell division. Astrocytes are star-shaped glial cells that have also been observed to turn into neurons by virtue of the stem cell characteristic pluripotency. Neurogenesis largely ceases during adulthood in most areas of the brain. However, there is strong evidence for generation of substantial numbers of new neurons in two brain areas, the hippocampus and olfactory bulb.
|Neuron (peripheral nervous system)|
A neuron is a specialized type of cell found in the bodies of all eumetozoans. Only sponges and a few other simpler animals lack neurons. The features that define a neuron are electrical excitability and the presence of synapses, which are complex membrane junctions that transmit signals to other cells. The body's neurons, plus the glial cells that give them structural and metabolic support, together constitute the nervous system. In vertebrates, the majority of neurons belong to the central nervous system, but some reside in peripheral ganglia, and many sensory neurons are situated in sensory organs such as the retina and cochlea.
A typical neuron is divided into three parts: the soma or cell body, dendrites, and 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 their farthest branches a few hundred micrometers from the soma. The axon leaves the soma at a swelling called the axon hillock, and can extend for great distances, giving rise to hundreds of branches. Unlike dendrites, an axon usually maintains the same diameter as it extends. The soma may give rise to numerous dendrites, but never to more than one axon. Synaptic signals from other neurons are received by the soma and dendrites; signals to other neurons are transmitted by the axon. A typical synapse, then, is a contact between the axon of one neuron and a dendrite or soma of another. Synaptic signals may be excitatory or inhibitory. If the net excitation received by a neuron over a short period of time is large enough, the neuron generates a brief pulse called an action potential, which originates at the soma and propagates rapidly along the axon, activating synapses onto other neurons as it goes.
Many neurons fit the foregoing schema in every respect, but there are also exceptions to most parts of it. There are no neurons that lack a soma, but there are neurons that lack dendrites, and others that lack an axon. Furthermore, in addition to the typical axodendritic and axosomatic synapses, there are axoaxonic (axon-to-axon) and dendrodendritic (dendrite-to-dendrite) synapses.
The key to neural function is the synaptic signaling process, which is partly electrical and partly chemical. The electrical aspect depends on properties of the neuron's membrane. Like all animal cells, the cell body of every neuron is enclosed by a plasma membrane, a bilayer of lipid molecules with many types of protein structures embedded in it. A lipid bilayer is a powerful electrical insulator, but in neurons, many of the protein structures embedded in the membrane are electrically active. These include ion channels that permit electrically charged ions to flow across the membrane and ion pumps that actively transport ions from one side of the membrane to the other. Most ion channels are permeable only to specific types of ions. Some ion channels are voltage gated, meaning that they can be switched between open and closed states by altering the voltage difference across the membrane. Others are chemically gated, meaning that they can be switched between open and closed states by interactions with chemicals that diffuse through the extracellular fluid. The interactions between ion channels and ion pumps produce a voltage difference across the membrane, typically a bit less than 1/10 of a volt at baseline. This voltage has two functions: first, it provides a power source for an assortment of voltage-dependent protein machinery that is embedded in the membrane; second, it provides a basis for electrical signal transmission between different parts of the membrane.
Neurons communicate by chemical and electrical synapses in a process known as neurotransmission, also called synaptic transmission. The fundamental process that triggers the release of neurotransmitters 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.
Anatomy and histology
Neurons are highly specialized for the processing and transmission of cellular signals. Given their diversity of functions performed in different parts of the nervous system, there is a wide variety in their shape, size, and electrochemical properties. For instance, the soma of a neuron can vary from 4 to 100 micrometers in diameter.
- The soma is the body of the neuron. As it contains the nucleus, most protein synthesis occurs here. The nucleus can range from 3 to 18 micrometers in diameter.
- The dendrites of a neuron are cellular extensions with many branches. This overall shape and structure is referred to metaphorically as a dendritic tree. This is where the majority of input to the neuron occurs via the dendritic spine.
- The axon is a finer, cable-like projection that 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 electrophysiological 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 to communicate with target neurons.
The accepted view of the neuron attributes dedicated functions to its various anatomical components; however, 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 motor neuron can be over a meter long, reaching from the base of the spine to the toes.
Sensory neurons can have axons that run from the toes to the posterior column of the spinal cord, 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).
Fully differentiated neurons are permanently postmitotic; however, research starting around 2002 shows that additional neurons throughout the brain can originate from neural stem cells through the process of neurogenesis. These are found throughout the brain, but are particularly concentrated in the subventricular zone and subgranular zone.
Histology and internal structure
Numerous microscopic clumps called Nissl substance (or Nissl bodies) are seen when nerve cell bodies are stained with a basophilic ("base-loving") dye. These structures consist of rough endoplasmic reticulum and associated ribosomal RNA. Named after German psychiatrist and neuropathologist Franz Nissl (1860–1919), they are involved in protein synthesis and their prominence can be explained by the fact that nerve cells are very metabolically active. Basophilic dyes such as aniline or (weakly) haematoxylin highlight negatively charged components, and so bind to the phosphate backbone of the ribosomal RNA.
The cell body of a neuron is supported by a complex mesh of structural proteins called neurofilaments, which are assembled into larger neurofibrils. Some neurons also contain pigment granules, such as neuromelanin (a brownish-black pigment that is byproduct of synthesis of catecholamines), and lipofuscin (a yellowish-brown pigment), both of which accumulate with age. Other structural proteins that are important for neuronal function are actin and the tubulin of microtubules. Actin is predominately found at the tips of axons and dendrites during neuronal development. There the actin dynamics can be modulated via an interplay with microtubule.
There are different internal structural characteristics between axons and dendrites. Typical axons almost never contain ribosomes, except some in the initial segment. Dendrites contain granular endoplasmic reticulum or ribosomes, in diminishing amounts as the distance from the cell body increases.
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 with short axons, which can often be confused with dendrites. 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 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.
Most neurons can be anatomically characterized as:
- Unipolar: only 1 process
- Bipolar: 1 axon and 1 dendrite
- Multipolar: 1 axon and 2 or more dendrites
- Anaxonic: where the axon cannot be distinguished from the dendrite(s).
- pseudounipolar: 1 process which then serves as both an axon and a dendrite
Furthermore, some unique neuronal types can be identified according to their location in the nervous system and distinct shape. Some examples are:
- Basket cells, interneurons that form a dense plexus of terminals around the soma of target cells, found in the cortex and cerebellum.
- Betz cells, large motor neurons.
- Lugaro cells, interneurons of the cerebellum.
- 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.
- Unipolar brush cells, interneurons with unique dendrite ending in a brush-like tuft.
- Granule cells, a type of Golgi II neuron.
- Anterior horn cells, motoneurons located in the spinal cord.
- Spindle cells, interneurons that connect widely separated areas of the brain
- Afferent neurons convey information from tissues and organs into the central nervous system and are also called sensory neurons.
- Efferent neurons transmit signals from the central nervous system to the effector cells and are also called motor neurons.
- Interneurons connect neurons within specific regions of the central nervous system.
Afferent and efferent also refer generally to neurons that, respectively, bring information to or send information from the brain.
Action on other neurons
A neuron affects other neurons by releasing a neurotransmitter that binds to chemical receptors. The effect upon the postsynaptic neuron is determined not by the presynaptic 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).
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, and have effects that are excitatory at ionotropic receptors and a modulatory effect at metabotropic receptors. 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 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 postsynaptic 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 others still. For example, photoreceptor cells 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. 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.
It is possible to identify the type of inhibitory effect a presynaptic neuron will have on a postsynaptic neuron, based on the proteins the presynaptic neuron expresses. Parvalbumin-expressing neurons typically dampen the output signal of the postsynaptic neuron in the visual cortex, whereas somatostatin-expressing neurons typically block dendritic inputs to the postsynaptic neuron.
- Tonic or regular spiking. Some neurons are typically constantly (or tonically) active, typically firing at a constant frequency. Example: interneurons in neurostriatum.
- Phasic or bursting. Neurons that fire in bursts are called phasic.
- Fast spiking. Some neurons are notable for their high firing rates, for example some types of cortical inhibitory interneurons, cells in globus pallidus, retinal ganglion cells.
Classification by neurotransmitter production
- Cholinergic neurons—acetylcholine. Acetylcholine is released from presynaptic neurons into the synaptic cleft. It acts as a ligand for both ligand-gated ion channels and metabotropic (GPCRs) muscarinic receptors. Nicotinic receptors are pentameric ligand-gated ion channels composed of alpha and beta subunits that bind nicotine. Ligand binding opens the channel causing influx of Na+ depolarization and increases the probability of presynaptic neurotransmitter release. Acetylcholine is synthesized from choline and acetyl coenzyme A.
- GABAergic neurons—gamma aminobutyric acid. GABA is one of two neuroinhibitors in the central nervous system (CNS), the other being Glycine. GABA has a homologous function to ACh, gating anion channels that allow Cl− ions to enter the post synaptic neuron. Cl− causes hyperpolarization within the neuron, decreasing the probability of an action potential firing as the voltage becomes more negative (recall that for an action potential to fire, a positive voltage threshold must be reached). GABA is synthesized from glutamate neurotransmitters by the enzyme glutamate decarboxylase.
- Glutamatergic neurons—glutamate. Glutamate is one of two primary excitatory amino acid neurotransmitter, the other being Aspartate. Glutamate receptors are one of four categories, three of which are ligand-gated ion channels and one of which is a G-protein coupled receptor (often referred to as GPCR).
- AMPA and Kainate receptors both function as cation channels permeable to Na+ cation channels mediating fast excitatory synaptic transmission
- NMDA receptors are another cation channel that is more permeable to Ca2+. The function of NMDA receptors is dependant on Glycine receptor binding as a co-agonist within the channel pore. NMDA receptors do not function without both ligands present.
- Metabotropic receptors, GPCRs modulate synaptic transmission and postsynaptic excitability.
- Glutamate can cause excitotoxicity when blood flow to the brain is interrupted, resulting in brain damage. When blood flow is suppressed, glutamate is released from presynaptic neurons causing NMDA and AMPA receptor activation more so than would normally be the case outside of stress conditions, leading to elevated Ca2+ and Na+ entering the post synaptic neuron and cell damage. Glutamate is synthesized from the amino acid glutamine by the enzyme glutamate synthase.
- Dopaminergic neurons—dopamine. Dopamine is a neurotransmitter that acts on D1 type (D1 and D5) Gs coupled receptors, which increase cAMP and PKA, and D2 type (D2, D3, and D4) receptors, which activate Gi-coupled receptors that decrease cAMP and PKA. Dopamine is connected to mood and behavior and modulates both pre and post synaptic neurotransmission. Loss of dopamine neurons in the substantia nigra has been linked to Parkinson's disease. Dopamine is synthesized from the amino acid tyrosine. Tyrosine is catalyzed into levadopa (or L-DOPA) by tyrosine hydroxlase, and levadopa is then converted into dopamine by amino acid decarboxylase.
- Serotonergic neurons—serotonin. Serotonin (5-Hydroxytryptamine, 5-HT) can act as excitatory or inhibitory. Of the four 5-HT receptor classes, 3 are GPCR and 1 is ligand gated cation channel. Serotonin is synthesized from tryptophan by tryptophan hydroxylase, and then further by aromatic acid decarboxylase. A lack of 5-HT at postsynaptic neurons has been linked to depression. Drugs that block the presynaptic serotonin transporter are used for treatment, such as Prozac and Zoloft.
Neurons communicate with one another via synapses, where the axon terminal or en passant bouton (a type of terminal located along the length of the axon) of one cell contacts 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 either increase or decrease activity in the target neuron, respectively. 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. High cytosolic calcium in the axon terminal also triggers mitochondrial calcium uptake, which, in turn, activates mitochondrial energy metabolism to produce ATP to support continuous neurotransmission.
An autapse is a synapse in which a neuron's axon connects to its own dendrites.
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).
Mechanisms for propagating action potentials
In 1937, John Zachary Young suggested that the squid giant axon could be used to study neuronal electrical properties. 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 that 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. 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.
Neural coding is concerned with how sensory and other information is represented in the brain by neurons. The main goal of studying neural coding is to characterize the relationship between the stimulus and the individual or ensemble neuronal responses, and the relationships amongst the electrical activities of the neurons within the ensemble. It is thought that neurons can encode both digital and analog information.
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. Greater intensity of stimulation does not produce a stronger signal but can produce a higher frequency of firing. There are different types of receptor responses to stimuli, 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 have 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 causes the corpuscle to change shape again. Other types of adaptation are important in extending the function of a number of other neurons.
The neuron's place as the primary functional unit of the nervous system was first recognized in the late 19th century through the work of the Spanish anatomist Santiago Ramón y Cajal.
To make the structure of individual neurons visible, Ramón y Cajal improved a silver staining process that had been developed by Camillo Golgi. The improved process involves a technique called "double impregnation" and is still in use today.
In 1888 Ramón y Cajal published a paper about the bird cerebellum. In this paper, he tells he could not find evidence for anastomis between axons and dendrites and calls each nervous element "an absolutely autonomous canton." This became known as the neuron doctrine, one of the central tenets of modern neuroscience.
In 1891 the German anatomist Heinrich Wilhelm Waldeyer wrote a highly influential review about the neuron doctrine in which he introduced the term neuron to describe the anatomical and physiological unit of the nervous system.
The silver impregnation stains are 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.
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.
Later discoveries yielded a few refinements to the simplest form of the doctrine. For example, glial cells, which are not considered neurons, play an essential role in information processing. Also, electrical synapses are more common than previously thought, 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 axons.
Ramón y 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. The Law of Dynamic Polarization has important exceptions; dendrites can serve as synaptic output sites of neurons and axons can receive synaptic inputs.
Neurons in the brain
The number of neurons in the brain varies dramatically from species to species. In a human, there are an estimated 10–20 billion neurons in the cerebral cortex and 55–70 billion neurons in the cerebellum. By contrast, the nematode worm Caenorhabditis elegans has just 302 neurons, making it an ideal model organism as scientists have been able to map all of its neurons. The fruit fly Drosophila melanogaster, a common subject in biological experiments, 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.
Charcot–Marie–Tooth disease (CMT) is a heterogeneous inherited disorder of nerves (neuropathy) that is characterized by loss of muscle tissue and touch sensation, predominantly in the feet and legs but also in the hands and arms in the advanced stages of disease. Presently incurable, this disease is one of the most common inherited neurological disorders, with 36 in 100,000 affected.
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), and recognition (agnosia), and functions such as decision-making and planning become impaired.
Parkinson's disease (PD), also known as Parkinson disease, 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 during simple activities. 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 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 and chronic inflammatory demyelinating polyneuropathy.
Although most injury responses include a calcium influx signaling to promote resealing of severed parts, axonal injuries initially lead to acute axonal degeneration, 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 peripheral nervous system (PNS), and longer in the CNS. The signaling pathways leading to axolemma degeneration are currently unknown.
It has been demonstrated that neurogenesis can sometimes occur in the adult vertebrate brain, a finding that led to controversy in 1999. Later studies of the age of human neurons suggest that this process occurs only for a minority of cells, and a vast majority of neurons composing the neocortex were formed before birth and persist without replacement.
The body contains a variety of stem cell types that have the capacity to differentiate into neurons. A report in Nature suggested that researchers had found a way to transform human skin cells into working nerve cells using a process called transdifferentiation in which "cells are forced to adopt new identities".
It is often possible for peripheral axons to regrow if they are severed, but a neuron cannot be functionally replaced by one of another type (Llinás' law).
- Wade, Nicholas (1999-10-15). "Brain may grow new cells daily". The New York Times.
- Nowakowski RS (August 2006). "Stable neuron numbers from cradle to grave". Proceedings of the National Academy of Sciences of the United States of America. 103 (33): 12219–20. Bibcode:2006PNAS..10312219N. doi:10.1073/pnas.0605605103. PMC 1567859
. PMID 16894140.
- Rutecki PA (April 1992). "Neuronal excitability: voltage-dependent currents and synaptic transmission". Journal of Clinical Neurophysiology. 9 (2): 195–211. doi:10.1097/00004691-199204010-00003. PMID 1375602.
- Davies, Melissa (2002-04-09). "The Neuron: size comparison". Neuroscience: A journey through the brain. Retrieved 2009-06-20.
- Chudler EH. "Brain Facts and Figures". Neuroscience for Kids. Retrieved 2009-06-20.
- Herrup K, Yang Y (May 2007). "Cell cycle regulation in the postmitotic neuron: oxymoron or new biology?". Nature Reviews. Neuroscience. 8 (5): 368–78. doi:10.1038/nrn2124. PMID 17453017.
- Alvarez-Buylla A, Garcia-Verdugo JM (February 2002). "Neurogenesis in adult subventricular zone". The Journal of Neuroscience. 22 (3): 629–34. CiteSeerX 10.1.1.337.738
. PMID 11826091.
- State Hospitals Bulletin. State Commission in Lunacy. 1897. p. 378.
- Zecca L, Gallorini M, Schünemann V, Trautwein AX, Gerlach M, Riederer P, Vezzoni P, Tampellini D (March 2001). "Iron, neuromelanin and ferritin content in the substantia nigra of normal subjects at different ages: consequences for iron storage and neurodegenerative processes". Journal of Neurochemistry. 76 (6): 1766–73. doi:10.1046/j.1471-4159.2001.00186.x. PMID 11259494.
- Herrero MT, Hirsch EC, Kastner A, Luquin MR, Javoy-Agid F, Gonzalo LM, Obeso JA, Agid Y (1993). "Neuromelanin accumulation with age in catecholaminergic neurons from Macaca fascicularis brainstem". Developmental Neuroscience. 15 (1): 37–48. doi:10.1159/000111315. PMID 7505739.
- Brunk UT, Terman A (September 2002). "Lipofuscin: mechanisms of age-related accumulation and influence on cell function". Free Radical Biology & Medicine. 33 (5): 611–9. doi:10.1016/s0891-5849(02)00959-0. PMID 12208347.
- Zhao B, Meka DP, Scharrenberg R, König T, Schwanke B, Kobler O, Windhorst S, Kreutz MR, Mikhaylova M, Calderon de Anda F (August 2017). "Microtubules Modulate F-actin Dynamics during Neuronal Polarization". Scientific Reports. 7 (1): 9583. Bibcode:2017NatSR...7.9583Z. doi:10.1038/s41598-017-09832-8. PMID 28851982.
- Lee WC, Huang H, Feng G, Sanes JR, Brown EN, So PT, Nedivi E (February 2006). "Dynamic remodeling of dendritic arbors in GABAergic interneurons of adult visual cortex". PLoS Biology. 4 (2): e29. doi:10.1371/journal.pbio.0040029. PMC 1318477
. PMID 16366735.
- Al, Martini, Frederic Et. Anatomy and Physiology' 2007 Ed.2007 Edition. Rex Bookstore, Inc. p. 288. ISBN 978-971-23-4807-5.
- Gerber U (January 2003). "Metabotropic glutamate receptors in vertebrate retina". Documenta Ophthalmologica. Advances in Ophthalmology. 106 (1): 83–7. doi:10.1023/A:1022477203420. PMID 12675489.
- Wilson NR, Runyan CA, Wang FL, Sur M (August 2012). "Division and subtraction by distinct cortical inhibitory networks in vivo". Nature. 488 (7411): 343–8. Bibcode:2012Natur.488..343W. doi:10.1038/nature11347. PMC 3653570
. PMID 22878717.
- Llinás RR (2014-01-01). "Intrinsic electrical properties of mammalian neurons and CNS function: a historical perspective". Frontiers in Cellular Neuroscience. 8: 320. doi:10.3389/fncel.2014.00320. PMC 4219458
. PMID 25408634.
- Kolodin YO, Veselovskaia NN, Veselovsky NS, Fedulova SA. Ion conductances related to shaping the repetitive firing in rat retinal ganglion cells. Acta Physiologica Congress.
- "Ionic conductances underlying excitability in tonically firing retinal ganglion cells of adult rat". Ykolodin.50webs.com. 2008-04-27. Retrieved 2013-02-16.
- Ivannikov MV, Macleod GT (June 2013). "Mitochondrial free Ca²⁺ levels and their effects on energy metabolism in Drosophila motor nerve terminals". Biophysical Journal. 104 (11): 2353–61. Bibcode:2013BpJ...104.2353I. doi:10.1016/j.bpj.2013.03.064. PMC 3672877
. PMID 23746507.
- Drachman DA (June 2005). "Do we have brain to spare?". Neurology. 64 (12): 2004–5. doi:10.1212/01.WNL.0000166914.38327.BB. PMID 15985565.
- Chudler EH. "Milestones in Neuroscience Research". Neuroscience for Kids. Retrieved 2009-06-20.
- Patlak J, Gibbons R (2000-11-01). "Electrical Activity of Nerves". Action Potentials in Nerve Cells. Archived from the original on August 27, 2009. Retrieved 2009-06-20.
- Brown EN, Kass RE, Mitra PP (May 2004). "Multiple neural spike train data analysis: state-of-the-art and future challenges". Nature Neuroscience. 7 (5): 456–61. doi:10.1038/nn1228. PMID 15114358.
- Thorpe, SJ (1990) Spike arrival times: A highly efficient coding scheme for neural networks. In R. Eckmiller, G. Hartmann, & G. Hauske (Eds.) Parallel processing in neural systems, Elsevier, pp. 91–94 ISBN 0444883908
- Eckert R, Randall D (1983). Animal physiology: mechanisms and adaptations. San Francisco: W.H. Freeman. p. 239. ISBN 0-7167-1423-X.
- López-Muñoz F, Boya J, Alamo C (October 2006). "Neuron theory, the cornerstone of neuroscience, on the centenary of the Nobel Prize award to Santiago Ramón y Cajal". Brain Research Bulletin. 70 (4-6): 391–405. doi:10.1016/j.brainresbull.2006.07.010. PMID 17027775.
- Finger, Stanley (1994). Origins of neuroscience : a history of explorations into brain function. Oxford University Press. p. 47. ISBN 9780195146943. OCLC 27151391.
Ramon y Cajal's first paper on the Golgi stain was on the bird cerebellum, and it appeared in the Revista in 1888. He acknowledged that he found the nerve fibers to be very intricate, but stated that he could find no evidence for either axons or dendrites undergoing anastomosis and forming nets. He called each nervous element "an absolutely autonomous canton".
- Finger, Stanley (1994). Origins of neuroscience : a history of explorations into brain function. Oxford University Press. p. 47. ISBN 9780195146943. OCLC 27151391.
... a man who would write a highly influential review of the evidence in favor of the neuron doctrine two years later. In his paper, Waldeyer (1891), ... , wrote that nerve cells terminate freely with end arborizations and that the "neuron" is the anatomical and physiological unit of the nervous system. The word "neuron" was born this way.
- "Whonamedit - dictionary of medical eponyms". www.whonamedit.com.
Today, Wilhelm von Waldeyer-Hartz is remembered as the founder of the neurone theory, coining the term "neurone" to describe the cellular function unit of the nervous system and enunciating and clarifying that concept in 1891.
- Grant G (October 2007). "How the 1906 Nobel Prize in Physiology or Medicine was shared between Golgi and Cajal". Brain Research Reviews. 55 (2): 490–8. doi:10.1016/j.brainresrev.2006.11.004. PMID 17306375.
- Witcher MR, Kirov SA, Harris KM (January 2007). "Plasticity of perisynaptic astroglia during synaptogenesis in the mature rat hippocampus". Glia. 55 (1): 13–23. CiteSeerX 10.1.1.598.7002
. doi:10.1002/glia.20415. PMID 17001633.
- Connors BW, Long MA (2004). "Electrical synapses in the mammalian brain" (PDF). Annual Review of Neuroscience. 27 (1): 393–418. doi:10.1146/annurev.neuro.26.041002.131128. PMID 15217338.
- Guillery RW (June 2005). "Observations of synaptic structures: origins of the neuron doctrine and its current status". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 360 (1458): 1281–307. doi:10.1098/rstb.2003.1459. PMC 1569502
. PMID 16147523.
- Sabbatini R.M.E. April–July 2003. Neurons and Synapses: The History of Its Discovery. Brain & Mind Magazine, 17. Retrieved March 19, 2007.
- Djurisic M, Antic S, Chen WR, Zecevic D (July 2004). "Voltage imaging from dendrites of mitral cells: EPSP attenuation and spike trigger zones". The Journal of Neuroscience. 24 (30): 6703–14. doi:10.1523/JNEUROSCI.0307-04.2004. PMID 15282273.
- Cochilla AJ, Alford S (March 1997). "Glutamate receptor-mediated synaptic excitation in axons of the lamprey". The Journal of Physiology. 499 ( Pt 2) (Pt 2): 443–57. doi:10.1113/jphysiol.1997.sp021940. PMC 1159318
. PMID 9080373.
- Williams RW, Herrup K (1988). "The control of neuron number". Annual Review of Neuroscience. 11 (1): 423–53. doi:10.1146/annurev.ne.11.030188.002231. PMID 3284447.
- von Bartheld CS, Bahney J, Herculano-Houzel S (December 2016). "The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting". The Journal of Comparative Neurology. 524 (18): 3865–3895. doi:10.1002/cne.24040. PMC 5063692
. PMID 27187682.
- Krajewski KM, Lewis RA, Fuerst DR, Turansky C, Hinderer SR, Garbern J, Kamholz J, Shy ME (July 2000). "Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A". Brain. 123 ( Pt 7) (7): 1516–27. doi:10.1093/brain/123.7.1516. PMID 10869062.
- "About Alzheimer's Disease: Symptoms". National Institute on Aging. Archived from the original on 15 January 2012. Retrieved 28 December 2011.
- Burns A, Iliffe S (February 2009). "Alzheimer's disease". BMJ. 338: b158. doi:10.1136/bmj.b158. PMID 19196745. (Subscription required (. ))
- Querfurth HW, LaFerla FM (January 2010). "Alzheimer's disease". The New England Journal of Medicine. 362 (4): 329–44. doi:10.1056/NEJMra0909142. PMID 20107219.
- "Parkinson's Disease Information Page". NINDS. 30 June 2016. Archived from the original on 4 January 2017. Retrieved 18 July 2016.
- "Movement Disorders". The International Neuromodulation Society.
- Wadep N (1999-10-15). "Brain may grow new cells daily". The New York Times. Retrieved 2013-02-16.
- Callaway, Ewen (26 May 2011). "How to make a human neuron". NatureNews. doi:10.1038/news.2011.328.
By transforming cells from human skin into working nerve cells, researchers may have come up with a model for nervous-system diseases and perhaps even regenerative therapies based on cell transplants. The achievement, reported online today in Nature, is the latest in a fast-moving field called transdifferentiation, in which cells are forced to adopt new identities. In the past year, researchers have converted connective tissue cells found in skin into heart cells, blood cells, and liver cells.
- Yiu G, He Z (August 2006). "Glial inhibition of CNS axon regeneration". Nature Reviews. Neuroscience. 7 (8): 617–27. doi:10.1038/nrn1956. PMC 2693386
. PMID 16858390.
- 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.
- Richard S. Snell: Clinical neuroanatomy (Lippincott Williams & Wilkins, Ed.6th 2006) Philadelphia, Baltimore, New York, London. ISBN 978-963-226-293-2
- 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
- Neurobiology at Curlie (based on DMOZ)
- IBRO (International Brain Research Organization). Fostering neuroscience research especially in less well-funded countries.
- NeuronBank an 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 – Neuron via the Neuroscience Information Framework
- Cell Centered Database – Neuron
- Complete list of neuron types according to the Petilla convention, at NeuroLex.
- NeuroMorpho.Org an online database of digital reconstructions of neuronal morphology.
- Immunohistochemistry Image Gallery: Neuron
- Khan Academy: Anatomy of a neuron
- Neuron images