From Wikipedia, the free encyclopedia
This
schematic shows an anatomically accurate single pyramidal neuron, the
primary excitatory neuron of cerebral cortex, with a synaptic connection
from an incoming axon onto a dendritic spine.
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 cause everything from
muscle contractions and affect
glandular outputs.
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.
[1][2]
Overview
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.
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
Diagram of a typical myelinated vertebrate motor
neuron
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]
- 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.
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;
[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]
Histology and internal structure
Golgi-stained neurons in human hippocampal tissue
Actin filaments in a mouse Cortical Neuron in culture
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.
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.
[12]
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.
Classification
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.
Structural classification
Polarity
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
- 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
Other
Furthermore,
some unique neuronal types can be identified according to their
location in the nervous system and distinct shape. Some examples are:
- Basket cells, 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
Functional classification
Direction
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.
[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.
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]
Discharge patterns
Neurons have intrinsic electroresponsive properties like intrinsic transmembrane voltage
oscillatory patterns.
[17] So neurons can be classified according to their
electrophysiological characteristics:
- Tonic or regular spiking. Some neurons are typically constantly (or tonically) active. Example: interneurons in neurostriatum.
- Phasic or bursting. Neurons that fire in bursts are called phasic.
- Fast spiking. Some neurons are notable for their high firing rates, for example some types of cortical inhibitory interneurons, cells in globus pallidus, retinal ganglion cells.[18][19]
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.
Connectivity
A signal propagating down an axon to the cell body and dendrites of the next cell
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.
[20]
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 10
11
(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 10
15 synapses (1 quadrillion). This number declines with age, stabilizing by adulthood. Estimates vary for an adult, ranging from 10
14 to 5 x 10
14 synapses (100 to 500 trillion).
[21]
An
annotated diagram of the stages of an action potential propagating down
an axon including the role of ion concentration and pump and channel
proteins.
Mechanisms for propagating action potentials
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.
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 (Ca
2+).
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.
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
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]
All-or-none principle
The conduction of nerve impulses is an example of an
all-or-none
response. In other words, if a neuron responds at all, then it must
respond completely. 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.
[26]
History
Drawing of a Purkinje cell in the
cerebellar cortex done by Santiago Ramón y Cajal, demonstrating the ability of Golgi's staining method to reveal fine detail
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]
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.
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]
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]
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]
Neuron doctrine
The
neuron doctrine is the now fundamental idea that neurons are the basic
structural and functional units of the nervous system. The theory was
put forward by Santiago Ramón y Cajal in the late 19th century. It held
that neurons are discrete cells (not connected in a meshwork), acting as
metabolically distinct units.
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]
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]
Neurons in the brain
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.
Neurological disorders
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.
[40]
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.
[41] 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.
[42][43]
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.
[44] Parkinson's disease belongs to a group of conditions called
movement disorders.
[45] 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
Guillain–Barré syndrome – demyelination
Demyelination
is the act of demyelinating, or the loss of the myelin sheath
insulating the nerves. When myelin degrades, conduction of signals along
the nerve can be impaired or lost, and the nerve eventually withers.
This leads to certain neurodegenerative disorders like
multiple sclerosis and
chronic inflammatory demyelinating polyneuropathy.
Axonal degeneration
Although
most injury responses include a calcium influx signaling to promote
resealing of severed parts, axonal injuries initially lead to acute
axonal degeneration, 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.
Neurogenesis
It has been demonstrated that
neurogenesis can sometimes occur in the adult
vertebrate brain, a finding that led to controversy in 1999.
[46]
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]
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".
[47]
Nerve regeneration
It is often possible for peripheral axons to regrow if they are severed,
[48] but a neuron cannot be functionally replaced by one of another type (
Llinás' law).
