CHAPTER 5: NERVOUS TISSUE

Phylogenetic development has led to the differentiation of cells in which the capacity for excitability
is particularly pronounced.

Nervous tissue is thus composed of two structural elements: nerve cells or neurons and glial cells,
or neuroglia.

 NERVE CELLS

Nerve cells have elongated processes (dendrites and axons) that form complex connections (synapses)
with other cells. Dendrites detect changes in their environment and transfer these signals to the cell
body (perikaryon), from which the stimulus is transmitted along the axon.

They are consistent in their basic structure (perikaryon, and a number of variably branching cell
processes). The nerve cell inclusive of its processes represents a genetic, morphologic, functional and
trophic unit referred to as a neuron. The perikaryon, comprising the nucleus and surrounding cytoplasm,
and the numerous dendrites constitute the receptive portion of the neuron.

Dendrites (Gk dendron = tree) are extensively branched, elongated processes. At their extremities, they
feature specific sensory receptors or form synapses with other neurons, from which they receive stimuli.
Dendrites conduct impulses towards the perikaryon. Each neuron has only one axon. Axons typically
exhibit terminal branching, forming the telodendritic zone. Individual free nerve endings, which vary in
number and form, terminate in end bulbs (boutons). These represent the effector component of the
neuron.

 Classification of Nerve Cells

Epithelial cells of the neural tube differentiate into bipotential progenitor cells, which give rise to
neurons and glial cells. After the glial cell line has split off, neuroblasts eventually differentiate into
mature neurons.

Based on the number of cell processes, neurons are classified as: Unipolar Neurons, Bipolar Neurons,
Pseudo-unipolar Neurons, and Multipolar Neurons.

o Unipolar Neurons - have a single cell process (axon). The cells of the first neural layer of the
retina (rods and cones) are frequently referred to as specialised unipolar neurons
o Bipolar Neurons - two processes (a dendrite and an axon) arise from opposite sides of the
perikaryon. These are relatively uncommon, constituting the middle neural layer of the retina,
the sensory cells of the olfactory mucosa and the cells of the spiral and vestibular ganglia of the
inner ear.
o Pseudo-unipolar Neurons - are found in the sensory ganglia of spinal and cranial nerves. This
type of nerve cell develops embryonically from a bipolar nerve cell. One of the two cell
processes extends into the central nervous system as the axon, while the other passes with the
anlage of the muscle and skin to the periphery to become the receptor portion of the cell. Both
axon and dendritic axon are part of the peripheral nervous system and both are myelinated.
 o Multipolar Neurons - Multipolar neurons are the most common type of nerve cell. The cells take
on a stellate appearance with multiple dendrites and a single axon. Multipolar neurons with a
particularly dense network of dendrites and a long axon are referred to as Golgi type I neurons.
These include lower motor neurons, Purkinje cells of the cerebellum and the pyramidal cells of
the cerebrum. Golgi type II neurons are primarily relay cells (interneurons) within the central
nervous system. Their cell processes are typically short but densely elaborated. Golgi type II cells
are found mostly in the cerebral and cerebellar cortex, and in the olfactory bulb. The neurons of
the autonomic ganglia are also multipolar.

 Neuronal Structure

neurons have two basic structural components:

· Perikaryon – nucleus and perinuclear cytoplasm

· Cell processes (dendrites, axon), frequently elongated.

o Perikaryon - ·
The cell body includes the nucleus and perinuclear cytoplasm. It is the site of metabolic
processes associated with cell maintenance and function. The cell body is usually round, oval or
polygonal, and reaches 100 μm in size (only 4–5 μm in Golgi type II neurons). The distinct
nucleus is typically spherical and euchromatic. It contains a nucleolus and sparse
heterochromatin. The marked development of the Golgi apparatus reflects the synthesis and
axonal transport of substances involved in neural transmission. Prompted the discoverer of this
organelle, the Italian scientist Camillo Golgi, to describe it as an apparato reticulare interno.
-Lysosomes, multivesicular bodies and lipid droplets are found in close association with the
Golgi apparatus. Also well-developed is the rough endoplasmic reticulum, which occupies a large
proportion of the cytoplasm in synthetically active cells. Together, the ribosomes and associated
rER are referred to as Nissl substance, after the German scientist Franz Nissl who first observed
them.
- The rER extends into the dendrites, but not into the axon. The ER-free site at which the axon
arises from the cell body is termed the axon hillock
- The endogenous pigment lipofuscin is usually also present, while melanin granules are
occasionally observed. Accumulation of lipofuscin is common in senescent nerve cells.
Neurofilaments and neurotubules (neuronal microtubules) are characteristic features of nerve
cells. Neurofilaments form aggregates (neurofibrils) that can be demonstrated using the Bodian
method
o Nerve Cell Processes: Dendrites
Dendrites are arborising processes that extend from the perikaryon of most neurons. The
organelles found in their primary stem and side branches are similar to those in the perikaryon.
Although the Golgi apparatus disappears with increased dendritic branching. The terminal
dendritic branches contain numerous neurofilaments, neurotubules and mitochondria that
facilitate dendritic transport. Distributed over the surface of the dendrites are numerous
axodendritic synapses, at which the dendrites regulate control circuits between various neuron.
o Nerve Cell Processes: Axons
 Arising from the cell body at the axon hillock, the axon conducts neural impulses away from the
cell body. The diameter of the axon (1–20 μm) is consistent along its length. The axonal
cytoplasm (axoplasm) is contained within a membrane referred to as the axolemma. At isolated
locations along their length, axons send out branches at right angles (collaterals). The axons of
postganglionic autonomic nerve fibres are not myelinated.

 Energy Supply and Axonal Transport Synapse

Mitochondria in the perikaryon, dendrites and axon are responsible for oxidative breakdown of glucose
or ketones. The resulting ATP provides energy for synthesis of proteins and RNA (for ongoing cell
renewal), for Na+/ K+-ATPase in the axolemma (for signal conduction) and for axonal transport systems.
Enzymes and proteins required at nerve synapses must be transported to the terminals via axonal
transport.

Axonal transport is categorised as fast (200–500 mm/ day) or slow (2–5 mm/day).

Antegrade transport systems (fast and slow) carry substances from the perikaryon to the synapse.

Retrograde systems (fast) return metabolic end products in the opposite direction, to the cell body.

o Synapse

Synapses are specialised intercellular junctions at which impulses are conducted by

electrical or chemical mechanisms from one neuron to another, or from a neuron to an
effector organ.

Electrical synapses consist of gap junctions that permit rapid transmission of impulses
across regions of reduced electrical resistance.

Chemical synapses are the main type of synapse, occurring predominantly at the end of an
axon. They consist of: · a presynaptic axonal component (synaptic end bulb), · the synaptic
cleft and · a postsynaptic component (postsynaptic membrane)

o Structure of a Chemical Synapse

Chemical synapses are largely consistent in their basic structure. The presynaptic axonal
component (synaptic end bulb, terminal bouton) is a bulbous expansion containing
mitochondria, smooth ER, neurotubules, neurofilaments and synaptic vesicles

The vesicles (20–60 nm) contain the chemical substances that transmit the nerve impulse
across the synapse (neurotransmitters). The plasmalemma of the nerve terminal is termed
the presynaptic membrane

The synaptic cleft lies between the pre- and postsynaptic membranes.

The postsynaptic component is rich in mitochondria. The plasmalemma of this region of the
receptor cell is termed the postsynaptic membrane.

Synapses can be categorised as:

· neurosensory synapses between neurons and sensory cells, e.g. in hearing and gustation
 · neuroglandular synapses between neurons and exocrine or endocrine glands

· neuromuscular synapses between neurons and skeletal muscle (motor end plates)

· interneuronal synapses including:

− axoaxonic synapses

− axodendritic synapses between axons and dendrites

− axosomatic synapses between axons and the perikaryon.

o Function of the Chemical Synapse

Chemical transmission of neural impulses at the synapse is performed by neurotransmitters.

Neurotransmitters of the peripheral nervous system include biogenic amines (e.g.
noradrenaline) and carboxylic acid esters (acetylcholine). In the central nervous system,
impulses are transmitted by biogenic amines (noradrenaline, dopamine, serotonin and
adrenaline), acetylcholine and other molecule classes.

Impulse transmission appears to proceed according to the same basic mechanism in all
synapses. The sequence of events comprises:

· release of the neurotransmitter from the presynaptic nerve terminal into the synaptic
cleft

· interaction of the neurotransmitters with specific postsynaptic receptors

· alteration of voltage across the postsynaptic membrane as a result of altered ion

permeability

· inactivation of the chemical signal by enzymatic cleavage of the neurotransmitter or

reuptake of the neurotransmitter by the nerve terminal.

A nerve impulse arriving at a synaptic end bulb (action potential) leads to transient
depolarisation of the presynaptic membrane.

Under the influence of the intracellular Ca2+ ions, synaptic vesicles are transported to the
presynaptic membrane (possibly with the aid of neurotubules) and neurotransmitters are
released into the synaptic cleft. The liberated neurotransmitter induces a local voltage change in
the postsynaptic membrane.

There are two main types of postsynaptic membrane receptors:

Ionotropic receptors contain ion channels, such that the conformational change induced
by binding of the neurotransmitter leads directly to opening of the associated channel.

Metabotropic receptors do not incorporate an ion channel, rather their intracellular

domain is linked to a G protein.
 Adrenergic receptors - Binding of the neurotransmitter alters the structure of the G
protein, resulting in the formation of a second messenger molecule that opens ion
channels located elsewhere in the membrane

Inactivation of the neurotransmitter occurs primarily through reuptake into the presynaptic
membrane.

o Neuromascular Synapse (Motor End Plate)

Motor end plates are specialised chemical synapses in which motor nerve fibres transmit
neural impulses to skeletal muscle. They are also referred to as neuromuscular (or
myoneural) junctions. Copious synaptic vesicles containing the neurotransmitter
acetylcholine are located in the free ends of the axon. The release of acetylcholine into the
synaptic cleft results in depolarisation of the plasmalemma of the muscle cell.
 Nerve Fiber

The term nerve fibre refers to the axon of a neuron and its outer covering. The latter is formed by glial
cells (oligodendrocytes in the central nervous system; forming white matter).

nerve fibres are divided into:

· somatic afferent sensory nerve fibres: convey impulses from the periphery to the spinal cord or brain,
and from some organs of special sense to the brain (e.g. the auditory and visual senses)

· somatic efferent motor nerve fibres: transmit impulses to the periphery (skeletal striated muscle)

· visceral afferent autonomic fibres

· visceral efferent autonomic fibres: parasympathetic and sympathetic involuntary nerve fibres that
regulate the function of the internal organs.

Nerve fibres that become invested in multiple concentric layers of glial cell cytoplasm are referred to as
myelinated fibres. In unmyelinated fibres, the nerve fibre occupies an invagination in the glial cell
cytoplasm.

o Myelinated Nerve Fibers

A large proportion of the nerve fibres of the peripheral and central nervous systems are
myelinated. The myelination process involves wrapping of the plasmalemma of the glial cell
around the central axon in slender, yet often numerous, lamellae, forming the so-called
myelin sheath. The sheath is formed by Schwann cells in the peripheral nervous system and
by oligodendrocytes in the central nervous system. The development of the myelin sheath is
phylogenetically significant with respect to differentiation of the nervous system. Myelin
sheaths increase the speed and distribution of the action potentials (depolarisation). The
sheath thus serves to isolate the axon from its surroundings, reducing current leakage. The
rate of axonal conduction increases with the thickness of the sheath: heavily myelinated
fibres conduct nerve impulses faster than those that are sparsely myelinated. A thick axon
transmits signals faster than a thin axon.

FORMATION OF THE MYELIN SHEATH:

The process of myelin sheath formation (myelinisation) occurs differently in the peripheral
and central nervous systems.

 Myelination of Peripheral Nerve Fibers

Each Schwann cell is associated with only one axon. Initially, the Schwann cell lies
adjacent to the axon, subsequently folding around it, displacing the axon to the centre.
Opposing surfaces of the plasmalemma approach one another, eventually fusing to form
a mesaxon. The mesaxon then extends around the axon to form lamellae. The lamellae,
in their entirety, constitute the myelin sheath. The outer portion of the Schwann cell,
 containing cytoplasm and the nucleus, adjoins the myelin sheath. This layer is referred
to as the sheath of Schwann.

 Myelination of Central Nerve Fibers

Numerous trapezoid processes extend from the oligodendrocyte, their free edges
becoming associated with, and wrapping around, multiple axons. These wrappings
together constitute the myelin sheath.

COMPOSITION OF THE MYELIN SHEATH:

Electron micrographs reveal the presence of parallel, alternating lipid and protein layers. Lipids,
mainly glycerine phosphatides, cholesterol and sphingolipids, make up around 70% of myelin.
The protein component (30%) includes proteolipids, glycoproteins and myelin basic protein. Due
to their high fat content, myelin sheaths can be demonstrated using lipid staining techniques.

Between two consecutive glial cells, the axon is exposed. This gap, 0.5 μm in width, is referred to
as the node of Ranvier. The section of the myelin sheath between two consecutive nodes is the
internode. Pockets of cytoplasm remain in the myelin sheath where fusion of the plasma
membrane of the glial cell is incomplete. These conical compartments, known as Schmidt–
Lanterman clefts

o Unmyelinated Nerve Fibers

In unmyelinated nerve fibres, the Schwann cell surrounds the axon without subsequent
wrapping by the mesaxon. In contrast to myelinated peripheral fibres, in which a Schwann
cell is associated with only one axon, several axons are usually surrounded by the same
Schwann cell in unmyelinated fibres.

o Generation and Conduction of Nerve Stimuli

The initiation and transmission of an electrical impulse occurs at the plasmalemma

(axolemma) of the neuron.

Opening or closing of the ion channels alters the distribution of charge across the
membrane and thus the membrane potential (voltage). An action potential is generated
when Na+ channels open in response to a depolarising stimulus. This influx exceeds the
efflux of K+ ions, altering the resting potential to create an action potential.

In myelinated fibres, the alteration of membrane potential can only occur at the nodes of
Ranvier. Consequently, the nerve impulses that give rise to the action potential ‘jump’ from
one node of Ranvier to the next. This is referred to as saltatory (discontinuous) conduction.

The speed of impulse conduction within a neuron is constant and is related to the structure
of the axon. Saltatory impulse transmission through myelinated fibres is faster than the type
of transmission that occurs in unmyelinated fibres. In addition, myelinated fibres require
less energy as the processes involved in impulse conduction are limited to the nodes of
Ranvier. In unmyelinated fibres, the conduction of nerve impulses to the synapse occurs in a
continuous wave over the surface of the axolemma.
 In the Erlanger–Gasser system, nerve fibres are classified as A, B or C on the basis of
diameter and conduction speed. A fibres are myelinated, rapidly conducting fibres that are
predominantly associated with muscle fibres, muscle spindles or skin.

Aα fibres (efferent and afferent innervation of muscle) are the thickest and fastest-
conducting fibres (10–20 μm and 60–120 m/s). Below these in speed and diameter are the
Aβ fibres (afferent fibres, touch and pressure) which measure 7–15 μm in diameter and
conduct at 40–90 m/s. With a diameter of 4–8 μm, Aγ fibres (efferent to muscle spindles)
are also relatively slow (30–45 m/s). Aδ fibres (3–5 μm) are slow-conducting fibres (5–25
m/s) involved in the monitoring of pain and temperature.

B fibres (1–3 μm) are myelinated fibres that conduct the action potentials of preganglionic
autonomic fibres at a moderate speed of 3–15 m/s.

C fibres are thin, unmyelinated nerve fibres (0.3–1 μm) that conduct very slowly (0.5–2
m/s). They serve to convey impulses in postganglionic autonomic nerve fibres.

 Nerves

The term ‘nerve’ applies to a bundle of peripheral nerve fibres that are combined by connective tissue
into single, variably sized entities. Nerves containing fibres with varying characteristics are referred to as
mixed nerves. Each nerve fibre (axon and associated supporting cells) is invested by one or, usually,
several layers of connective tissue.

o Nervous Tissue Investments

The endoneurium, this forms an incomplete casing around the nerve fibre. Together with
the basement membrane, the endoneurium forms the endoneurial sheath. Groups of nerve
fibres (fascicles) are enclosed in concentrically layered connective tissue septa (perineurium,
perineurial sheath). A dense, tough superficial connective tissue layer, the epineurium,
encloses the whole nerve.

o Regeneration of Nervous Tissue

Nerve cells cannot be replaced as they lose their ability to divide during the differentiation
process. However, peripheral nerves retain the capacity to regenerate through outgrowth of
the axon. The regeneration of axons is a complex process. Initially, degenerating nerve fibres
are degraded by phagocytosis. New nerve processes (neurites) sprout from the regenerating
axon, progressing along the columns at 1–2 mm per day. Within approximately 6 months,
the axon regains its original morphology.

 GLIAL CELLS

Glial cells are essential components of nervous tissue. Without them, nerve cells are unable to function.
Their functions include provision of nutrition and metabolic support to neurons and facilitation of the
conduction of nerve impulses by the formation of neural sheaths. Most nerve cells are closely related,
both structurally and functionally, to glial cells (neuroglia), with which they share a common embryonic
origin.

Specific functions performed by glial cells include:

· physical support by occupying the spaces between perikarya, dendrites and axons, thus contributing to
the organisation and spatial separation of neurons,

· metabolic support and exchange of substances between the nerve cells and capillaries,

· formation of the sheath of myelinated and unmyelinated nerve fibres, thus influencing the speed of
nerve impulse conduction,

· neuronal regeneration, in which they act as a physical guide,

· contribution to the blood–brain barrier and other interfaces in the central nervous system

· capacity for phagocytosis (certain cells).

Based on structural and functional criteria, glial cells are divided into:

· Glial cells of the central nervous system:

− ependymal cells,

− astrocytes,

− oligodendrocytes

− microglia (Hortega cells);

· Glial cells of the peripheral nervous system:

− Schwann cells (neurolemmocytes)

− satellite cells (amphicytes).

GLIAL CELLS OF THE CENTRAL NERVOUS SYSTEM

 Ependymal Cells

Ependymal cells are derived from the lining of the inner wall of the neural tube, remaining at their site
of origin for the duration of their life. These cuboidal to columnar cells form the epithelial lining of the
ventricles of the central nervous system (CNS) and the central canal of the spinal cord.

In its entirety, this epithelial layer serves as a functional barrier between the cavities of the nervous
system and the neurons. Within the ventricles, ependymal cells have a specialised secretory function
forming the epithelial lining of the choroid plexi which produce the cerebrospinal fluid.

In several areas of the CNS, an elongated process extending from the base of ependymal cells makes
contact with underlying capillaries. These ependymal cells are referred to as tanycytes. Tanycytes lack
cilia on their apical surface, allowing them to be distinguished from other, ciliated ependymal cells.
Tanycytes are sometimes also located in the central canal of the spinal cord.

 Astrocytes

Astrocytes are the largest glial cells in the central nervous system. Their processes make contact with
other neurons and with the pia mater. Terminal expansions of astrocyte processes (end feet) form the
glia limitans, a barrier membrane that covers the surface of the brain and spinal cord (membrana
limitans gliae superficialis) and separates intracerebral blood vessels from the brain (membrana limitans
gliae perivascularis). Astrocytes are thus a component of the blood–brain barrier.

Astrocytes play a prominent role in the migration of neurons during brain development and in
regulation of neurotransmitter activity astrocytes make an important contribution to repair and
regeneration of damaged CNS tissue. Astrocytes also participate in cell-mediated immunity within the
CNS.

Through the connections between their cell processes and neurons, astrocytes facilitate the transport of
fluid and metabolites between neurons and capillaries. Damage to this regulatory mechanism results in
swelling (oedema) of the nervous tissue.Based on their morphology, astrocytes can be classified as:

· protoplasmic astrocytes (astrocyti protoplasmatici)

· fibrous astrocytes (astrocyti fibrosi)

o Protoplasmic Astrocytes

Protoplasmic astrocytes are found predominantly in the grey matter of the central nervous
system. They are characterised by a polygonal perinuclear region (15–25 μm) and many
extensively branched cell processes.

o Fibrous Astrocytes

Fibrous astrocytes are located in the white matter of the brain and spinal cord. Measuring
10–12 μm near the nucleus, fibrous astrocytes exhibit long, sparsely branching processes
that lie parallel to nerve fibres.

 Oligodendrocytes

Oligodendrocytes are small glial cells (6–8 μm at the nucleus) occurring in the grey and white matter.
They are sometimes incorrectly described as ‘unbranched cells’. The electron microscope reveals 10–50
extensively flattened sheet-like processes that are responsible for myelination of nerve fibres within the
CNS

Oligodendrocytes exhibit morphological and functional differences, based on the region of the CNS in
which they are located:

· In white matter, oligodendrocytes are interfascicular cells, arranged in characteristic rows between
nerve fibres.

· In grey matter, oligodendrocytes form satellites of neurons or blood vessels, their processes being
closely associated with the perikaryon.
Perivascular oligodendrocytes are numerous and are prominent around the blood vessels of the
cerebral cortex. Interfascicular oligodendrocytes are by far the most common cell type in the white
matter.

oligodendrocytes are subdivided into four types (Hortega types I–IV)

Interfascicular oligodendrocytes are responsible for the formation and maintenance of the myelin
sheath of CNS nerve fibres, in which saltatory nerve conduction is an essential requirement. A key
component of iron metabolism in the CNS, requiring iron for synthesis of myelin.

 Microglia

Microglia, also named Hortega cells after the neurophysiologist Pio Del Rio Hortega (1882–1945), are
small, usually stellate glial cells, frequently located near blood vessels. Microglia are found in both the
grey and white matter. The phagocytic capacity of microglia reflects their differentiation from migrating
blood monocytes, macrophages, pericytes surrounding the walls of blood vessels or from the connective
tissue of the meninges. In view of their mesodermal origin, they have also been referred to historically
as mesoglia.

GLIAL CELLS OF THE PERIPHERA NERVOUS SYSTEM

 Schwann Cell

Schwann cells form the myelin sheath surrounding axons of peripheral nerves. The plasmalemma of the
Schwann cell wraps around the axon and differentiates into the myelin sheath. The ends of consecutive
Schwann cells are denoted by the node of Ranvier, where the myelin sheath is interrupted.

 Satellite Cell

Satellite cells surround the perikaryon of nerve cells in ganglia (autonomic, spinal, cranial nerves).
Satellite cells are functionally associated with capillaries and support the metabolic requirements of the
ganglion cells.