document_title: Neuron

question_text: where do you find neurons in the brain

question_tokens: where do you find neurons in the brain

text: Neuron

text: Overview[edit]

text:
Structure of a typical neuron

Neuron (peripheral nervous system)

Dendrite
Soma
Axon
Nucleus
Node of
Ranvier
Axon terminal
Schwann cell
Myelin sheath

text: 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[3] 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.

text: 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.

text: 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.

text: 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.

text: 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.

text: Anatomy and histology[edit]

text: 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.[4]

text:
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.[5]
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.

text: 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.

text: 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.

text: 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).

text: Fully differentiated neurons are permanently postmitotic;[6] 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.[7]

text: Histology and internal structure[edit]

text: 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 [8] highlight negatively charged components, and so bind to the phosphate backbone of the ribosomal RNA.

text: 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.[9][10][11] 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.[12]

text: 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.

text: Classification[edit]

text: Neurons exist in a number of different shapes and sizes and can be classified by their morphology and function.[14] 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.

text: Structural classification[edit]

text: Polarity[edit]

text: Most neurons can be anatomically characterized as:

text:
Unipolar: only 1 process
Bipolar: 1 axon and 1 dendrite
Multipolar: 1 axon and 2 or more 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.

Anaxonic: where the axon cannot be distinguished from the dendrite(s).
pseudounipolar: 1 process which then serves as both an axon and a dendrite

text: Other[edit]

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

text:
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

text: Functional classification[edit]

text: Direction[edit]

text:
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.

text: Afferent and efferent also refer generally to neurons that, respectively, bring information to or send information from the brain.

text: Action on other neurons[edit]

text: 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).

text: 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.

text: 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.[15] 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.

text: 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.[16]

text: Discharge patterns[edit]

text: Neurons have intrinsic electroresponsive properties like intrinsic transmembrane voltage oscillatory patterns.[17] So neurons can be classified according to their electrophysiological characteristics:

text:
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 high firing rates, for example some types of cortical inhibitory interneurons, cells in globus pallidus, retinal ganglion cells.[18][19]

text: Classification by neurotransmitter production[edit]

text:
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).

text:
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.

tag: ol

text:
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.

text: Connectivity[edit]

text: Neurons communicate with one another via synapses, where the axon terminal or en passant bouton (a type of terminals 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.[citation needed]

text: 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.[20]

text: An autapse is a synapse in which a neuron's axon connects to its own dendrites.

text: 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).[21]

text: Mechanisms for propagating action potentials[edit]

text: In 1937, John Zachary Young suggested that the squid giant axon could be used to study neuronal electrical properties.[22] 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.

text: 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+).

text: 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.[23] 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.

text: 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.

text: 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.

text: Neural coding[edit]

text: 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.[24] It is thought that neurons can encode both digital and analog information.[25]

text: All-or-none principle[edit]

text: 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.

text: 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.

text: 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.[26]

text: History[edit]

text: 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.[27]

text: To make the structure of individual neurons visible, Ramón y Cajal improved a silver staining process that had been developed by Camillo Golgi.[27] The improved process involves a technique called "double impregnation" and is still in use today.

text: 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."[27][28] This became known as the neuron doctrine, one of the central tenets of modern neuroscience.[27]

text: 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.[29][30]

text: 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.[31]

text: Neuron doctrine[edit]

text: 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.

text: 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.[32] Also, electrical synapses are more common than previously thought,[33] 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.[34]

text: 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.[35] The Law of Dynamic Polarization has important exceptions; dendrites can serve as synaptic output sites of neurons[36] and axons can receive synaptic inputs.[37]

text: Neurons in the brain[edit]

text: The number of neurons in the brain varies dramatically from species to species.[38] The adult human brain contains about 85-86 billion neurons,[38][39] of which 16.3 billion are in the cerebral cortex and 69 billion in the cerebellum.[39] 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. 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.

text: Neurological disorders[edit]

text: This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (February 2017) (Learn how and when to remove this template message)

text: 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 37 in 100,000 affected.

text: 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.

text: 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.

text: 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.

text: Demyelination[edit]

text: 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.

text: Axonal degeneration[edit]

text: 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.

text: Neurogenesis[edit]

text: It has been demonstrated that neurogenesis can sometimes occur in the adult vertebrate brain, a finding that led to controversy in 1999.[40] 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.[2]

text: 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".[41]

text: Nerve regeneration[edit]

text: It is often possible for peripheral axons to regrow if they are severed,[citation needed] but a neuron cannot be functionally replaced by one of another type (Llinás' law).[17]


document_title: Who Dat?

question_text: who dat say who dat when i say who dat origin

root

text: Who Dat?

text: Origins[edit]

text: The earliest documented use of the phrase can be found in a July 30, 1852 New Orleans Daily Picayune article.[2]

tag: p

text: The chant of "Who Dat?" originated in minstrel shows and vaudeville acts of the late 19th and early 20th centuries and was taken up by jazz and big band performers in the 1920s and '30s.[3]

text: Early references to "Who Dat?" can be found in the 19th Century in the poetry of Paul Laurence Dunbar, first in his poem "When Malindy Sings" and later in his lyrics to the song "Who Dat Say Chicken in dis Crowd,"[4][5][6] a featured song in Clorindy: The Origin of the Cakewalk, an "operetta" by Dunbar and Will Marion Cook that was first presented as part of E.E. Rice's 1898 show "Summer Nights".[7] A common tag line in the days of Negro minstrel shows was: "Who dat?" answered by "Who dat say who dat?"  Many different blackfaced gags played off that opening.  Vaudeville performer Mantan Moreland was known for the routine.[6]   Another example is "Swing Wedding", a 1930s Harman-Ising cartoon musical, which caricatured Fats Waller, Cab Calloway, Bill "Bojangles" Robinson, Ethel Waters, and the Mills Brothers as frogs in a swamp performing minstrel show jokes and jazz tunes. The frogs repeatedly used the phrase "who dat?"

text: In the swing era, "who dat" chants back and forth between the band and the band leader or between the audience and the band were extemporaneous. That is, there was no one specific set of words except for the two magic ones.

text: "Who Dat?" lyrics from 1937:

text: Who dat up there who's dat down there

text:
Who dat up there who dat well down there
Who's dat up there, sayin' who's dat down there
When I see you up there well who's dat down there

text:
Who dat inside who's dat outside
Who's dat inside who dat well outside
Who's dat inside, singin' who's dat outside
When I see up there well who's dat out there

text:
Button up your lip there big boy
Stop answerin' back
Give you a tip there big boy
Announce yourself jack

text:
Who dat up there who's dat down there
Who dat up there who dat, well down there
Who's dat up there, singin' who's dat down there
When I see you up there you bum
Well who's dat down there

text: Who dat

text: Staged minstrel skits featured frightened African American characters saying "who dat" when they encountered a ghost, or someone imitating a ghost. Then, the "who dat"–"who dat say who dat" skit would play itself out.  This skit was done frequently in short reels from the 1930s to 1950s and in some early TV shows too. Even the Marx Brothers had a "who dat" routine, which they included in their film A Day at the Races. "Who Dat Man?  Why It's Gabriel!"[6]  Often, a ghost was called a "who dat." Metro-Goldwyn-Mayer's animated character Bosko once had such an encounter in a 1938 toon called "Lil Ol Bosko in Bagdad." In 1941 Butterfly McQueen infamously delivered what African American film historian Donald Bogle described as what "might be the most demeaning line ever uttered by a black in the movies" when she said, "Who dat say who dat when I say who dat?" in the movie Affectionately Yours.[8]

text: "Who Dat?" became a familiar joke with soldiers during World War II.

text: Back in WWII, U.S. fighter squadron pilots would often fly under radio silence. But things get lonely up there in the cockpit, so after a while there'd be a crackle of static as someone keyed his mike. Then a disembodied voice would reply, "Who dat?"  An answer would come, "Who dat say who dat?" And another, "Who dat say who dat when ah say who dat?"  After a few rounds of this, the squadron commander would grab his microphone and yell, "Cut it out, you guys!"  A few moments of silence. Then... "Who dat?"[9]

text: Origins of the "Who Dat?" chant[edit]

text: "Who Dat" became part of a chant for fans cheering on their favorite team.  It has been debated exactly where it started, but some claim it began with Southern University Jaguars fans either in the late 1960s or early 1970s and went "Who dat talkin' 'bout beatin' dem Jags?"[10] Another claim is that it was connected with St. Augustine High School, a historically African-American all-boys Catholic high school in New Orleans, and yet another is that the cheer originated at Patterson High School in Patterson, Louisiana (home of Saints running back Dalton Hilliard).[6] In the late 1970s fans at Alcorn State University[11] and Louisiana State University picked up on the cheer.[12]  Fans of professional wrestler Junkyard Dog, a star on the Mid-South Wrestling circuit from 1979 to 1984 who frequently appeared in events at the Louisiana Superdome and Municipal Auditorium in New Orleans, had a similar chant: "Who dat think they gonna beat that Dog".[13]

text: Its earliest known documented link specifically to the Saints organization was actually a December 9, 1972 New Orleans Times–Picayune newspaper column reference to a player from an opposing team, Carl Garrett of the New England Patriots.[14]

text: By 1983 the cheer had become so popular among fans that the New Orleans Saints organization officially adopted it during the tenure of coach Bum Phillips, and Aaron Neville (along with local musicians Sal and Steve Monistere and Carlo Nuccio) recorded a version of "When the Saints Go Marching In" that incorporated the chant of "Who dat say dey gonna beat dem Saints" (performed by a group of Saints players). The song quickly became a major local hit, due in part to the support of sportscaster Ron Swoboda and the fact that Saints fans had been using the chant for some time.[6]

text: Meanwhile, in about 1981 Cincinnati Bengals fans and players had started with their similar "Who Dey" cheer ("Who Dey think gonna beat them Bengals?").[15] In a 2006 article, Toni Monkovic, a New York Times writer, speculated that the 1981 popularity of the Bengals' "Who Dey" may have led Saints fans to expand their use of "Who Dat", from the "small number, and possibly a very small number" of Saints fans using it in the late 1970s to the much wider use of the chant in 1983. Monkovic noted that the fan bases of the two teams continue to disagree about this, and that ultimately the evidence is unclear.[16] However, this speculation seems unlikely to be accurate as the "Who Dat" chant was so common at nearby LSU months before Cincinnati's 1981 Super Bowl run that a song called "Who Dat" had been written (in March 1981) to the tune of Frankie Smith's "Double Dutch Bus" and played regularly on local radio, in conjunction with the LSU men's basketball team's Final Four run.[17]

text: "Who Dat?" spin-off chants[edit]

text: After the Saints won the NFC Championship Game on January 24, 2010, against the Minnesota Vikings in the Superdome, fans from all across New Orleans, including fans who were exiting the game, started a Mardi Gras-style "Who Dat" on Bourbon Street with modified lyrics, chanting, "Who Dat, Who Dat, Who Dat in the Super Bowl!" in reference to the Saints advancing to the Super Bowl for the first time ever in their 43-year history.[18][19] In Super Bowl XLIV, on February 7, 2010, the Saints beat the Indianapolis Colts 31-17. "Drew Dat" has occasionally been used in honor of quarterback Drew Brees.

text: Who Dat Nation[edit]

text: In recent years the phrase "Who Dat Nation" has become a popular term for the entire community of Saints fans.[20][21][22]  According to Bobby Hebert, formerly a Saints quarterback and currently a sports commentator in New Orleans, the term "Who Dat Nation" originated after a highly anticipated 2006 game between the Saints and the favored Dallas Cowboys, which the Saints won; after the game, listeners from a wide geographic range called into Hebert's radio show on WWL (AM), and Hebert commented, "Man, there's a whole Who Dat Nation out there."[23]

text: Ownership controversy[edit]

text: In January 2010, the NFL sent cease and desist letters to several Louisiana T-shirt shop owners ordering them to cease producing T-shirts bearing the phrase "Who dat". According to some recipients of these letters, the NFL was claiming to own the trademark to the term "Who dat", and that unlicensed T-shirts bearing the phrase would cause confusion among fans of the Saints about the official status of the merchandise.[24][25][26] On January 27 one company tweeted about their whodat tee shirt cease and desist order from the NFL, and NewOrleans.com and Huffington Post interviewed the Monisteres about the NFL's claims in relation to their company Who Dat?, Inc. The next day, the brothers released a statement claiming rights to the phrase to NewOrleans.com, which they registered in 1983 after recording the version of "When the Saints Go Marching In" that incorporated the chant.[27] The Monistere's record is listed as inactive, meaning that it was not renewed upon expiration. The Saints organization, through their company The New Orleans Louisiana Saints Limited Partnership, also registered the mark "Who Dat" in 1988 when used in conjunction with "fleur-de-lis design",[28] but later the Saints released their claim of ownership to WhoDat, Inc., asserting that they owned the phrase.[29]

text: The NFL's action also provoked responses from U.S. Senator David Vitter and Congressman Charlie Melancon of Louisiana, among others.  Vitter sent a formal letter to NFL Commissioner Roger Goodell criticizing the NFL's attempt to claim ownership of the chant, informing Goodell he would be printing T-shirts using the phrase, and daring the NFL to sue him.[30]  It was later reported that the NFL had responded to Vitter's letter, stating that it was only seeking to prevent unauthorized uses of "Who Dat?" together with other identifying marks of the Saints.[31][32]

text: Louisiana Attorney General Buddy Caldwell called the NFL and had a conversation about the ownership of the "Who Dat" slogan and of the fleur-de-lis.  Caldwell said the bottom line from the legal back-and-forth with the league is that the NFL "is conceding it has no exclusive rights to the fleur-de-lis and no exclusive rights to 'Who Dat' and offshoots of 'Who Dat,' and no exclusive rights to the colors black and gold."  Caldwell said his office was drafting a document to be signed by the state and the NFL outlining what is and is not allowable.[33]

text: On March 4, 2010, the Monisteres' company, Who Dat? Inc., filed suit in federal court against the Saints, NFL Properties, and the state of Louisiana, alleging improper interference with their business interests. The suit alleges: in 1987 the New Orleans Saints were granted a license by Who Dat?, Inc. to use the Who Dat phrase; in that agreement, the Saints agreed that the mark was original and that Monistere was the first use owner of the trademark; the Saints also agreed to never challenge Monistere's ownership of the mark or aid any one else in doing so; and the Saints were to also help protect the mark from infringement by others on behalf of the licensors (Who Dat?, Inc.).[34][35][36][37]  Who Dat? Inc. subsequently amended their complaint to name several local retailers as defendants, most notably Fleurty Girl, and the matter was set for initial hearing in the U.S. District Court for the Eastern District of Louisiana on November 10, 2010.[38]

text: In January 2012, it was reported that the NFL and the Monisteres had agreed to dismiss their claims against each other and to cooperate in the production of "co-branded merchandise".[39]  The lawsuit continued as to some of the other defendants, pending hearing of their motions to dismiss the case.[40][41]  In October 2012 it was reported that the remaining parties had settled the case on confidential terms.[42]  According to one attorney and restaurant owner who had been a party to the case, "The net effect of the settlement is that nobody owns Who Dat".[43]

text: Recorded versions[edit]

text:
Who Dat - Spose
Who Dat? - Aaron Neville
Who Dat (Going to the Super Bowl) - Ashley Forrestier[44]
Who Dat - Royal Crown Revue
Dat "Who Dat" Jazz - Olympia Brass Band
Who Let the Dogs Out (Who Dat remix) - Baha Men/Clear Channel New Orleans
The Who Dat Roll - Williams Riley[45]
Who Dat? - Young Jeezy
Who Dat?  Tom Tom Club
Who Dat David Frizzell, #60 Country hit in 1984
Who Dat - J. Cole
Who Dat Girl - Flo Rida

tag: ul

text: In hip hop[edit]

text: In 2008, New Orleans based artist Lil Wayne referenced the chant in his hit single "A Milli" where he raps Who dat say dey gonna beat Lil Wayne even though he is a Green Bay Packers fan.

text: In 2009, New Orleans based artist K. Gates recorded "Black and Gold (Who Dat)" based on Ying Yang Twins' "Halftime (Get Crunk)".

text: "Who dat" is also used in the song "Holla Back" by New Orleans-based rapper Juvenile: "They want a pimp to give them some money, but I don't do that. But baby I'm a Saints fan that's why I say who dat."

text: "Who Dat" is the name of the 8th single from 2008 The Recession by Young Jeezy. They say who dat?

text: JT Money has a 1999 single called "Who Dat". The song was a hit, but was likely not intended to have any relation to the Saints or Vaudeville.

text: In 2009, New Orleans rapper Birdman chants a "Who Dat". in the Single Wasted(Remix) by Gucci Mane featuring Birdman, Jadakiss and Lil Wayne.

text: In 2010, rapper J. Cole recorded a song called "Who Dat".

text: In 2010, New Orleans native, Ashley Forrestier released "Who Dat (Going to the Super Bowl)" celebrating the New Orleans Saints 31-28 Overtime Win over the Minnesota Vikings in the 2009-10 NFC Championship Game.

text: In 2012, New Orleans based rapper G-Eazy, in collaboration with artists Mod Sun and Meta, released the song "Rappin' A$$ Rappers" in which G-Eazy raps "livin' in New Orleans where dem people holla 'Who Dat'".[44]

text: Australian hip-hop artist Iggy Azalea has employed the refrain in several songs, including "Fancy" and "Leave It", drawing criticism from some who perceive an appropriation of Southern Black culture.[46]

text: Other references[edit]

text: A deepwater oil and gas field in the Gulf of Mexico, discovered in 2007, was named "Who Dat" by its developer, LLOG Exploration Co.,  based in New Orleans. The field, encompassing Mississippi Canyon Blocks 503, 504 and 547 in about 3,000 feet of water, began production in 2011.[47]