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| School of Anatomy and Human Biology - The University of Western Australia
| Blue Histology - Nervous Tissue

Topics | Lab Guides and Images
Central Nervous System | Spinal Cord - LFB/CFV, H&E, silver stain
Neurones
Glia | Forebrain - GIEMSA stained, plastic embedded
Peripheral Nervous System | Peripheral Nerves - H&E, osmium
Peripheral Nerves
Ganglia | Spinal and Autonomic Ganglia - H&E

#### Additional Resources

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Large Images
  Search the Large Images page with the keywords "nervous tissue", "CNS", "PNS", "spinal cord", "nerve", "forebrain", "cortex", "grey matter", "white matter", "neurone", "ganglion cell", "glia", "myelin sheath" or "dendrites".
VScope
  Magnification & Stage Simulations
  nervous tissue, peripheral nerve, cat - osmium
  nervous tissue, cortex, mouse - Giemsa
  Focus & Stage Simulation:
  forebrain, mouse, cortex - Giemsa
  forebrain, rat, cortex - Golgi
Self Assessment
  Choose subject area "nervous tissue" on the Quiz page

### NERVOUS TISSUE

The nervous system consists of all nervous tissue in the body. It is divided anatomically into the central nervous system and the peripheral nervous system.

### Central Nervous System (CNS)

The CNS consists of the brain (encephalon), which is enclosed in the skull, and the spinal cord, which is contained within the vertebral canal. Nervous tissue of the CNS does not contain connective tissue other than that in the meninges and in the walls of large blood vessels. Collagenous fibers or fibrocytes/blasts are consequently not observed, which is quite unlike other tissues. Because of the absence of connective tissue, fresh CNS tissue has a very soft, somewhat jelly-like consistency. The two major classes of cells that make up the nervous tissue are nerve cells, neurones, and supporting cells, glia.

### Neurones

The vast majority of neurones is generated before birth. Persisting stem cells give rise to a small number of new neurones throughout the lifetime of mammals, including humans. The permanent addition of neurones may be important for the maintenance and plasticity of some parts of the CNS, but it is insufficient to replace neurones that die because of disease or acute damage to the CNS. Neurones are "intended" to last a lifetime. Mature neurones are not mitotically active, i.e. they do not divide.

Neurones are generally large cells. Neural activity and its control require the expression of many genes, which is reflected in the large and light nuclei of most neurones. The keys to the understanding of the function of a neurone lies in (1) the shape of the neurone and, in particular, its processes, (2) the chemicals the neurone uses to communicate with other neurones (neurotransmitters) and (3) the ways in which the neurone may react to the neurotransmitters released by other neurones.

The shape of the neurone and its processes Neurones have long processes (neurites), which extend from the part of the cell body around the nucleus, the perikaryon or soma. Neurites can be divided into two functionally and morphologically different groups, dendrites and axons. Dendrites are part of the receptive surface of the neurone. As a rule neurones have one to several primary dendrites, which emerge from the perikaryon. Primary dendrites may divide into secondary, tertiary etc. dendrites. Some dendrites are studded with small, mushroom-shaped appendages, which are called spines. Each neurone has as a rule one axon, and never more than one axon which emerges from the perikaryon or close to the trunks of one of the primary dendrites. The point of origin of the axon from the perikaryon is the axon hillock. The axon may, like the dendrites, branch as it travels through the nervous tissue to its destination(s). The axon is the "transmitting" process of the neurone. |

The axon forms small, bulb-shaped swellings called boutons at the ends (terminal boutons) or along the course (boutons en passant) of its branches. Synapses are morphologically specialised contacts between a bouton formed by one neurone, the presynaptic neurone, and the cell surface of another neurone, the postsynaptic neurone. Synaptic vesicles contain the neurotransmitters. Synaptic vesicles typically accumulate close to the site of contact between the bouton and the postsynaptic neurone. The release of the neurotransmitter from the synaptic vesicles into the synaptic cleft, i.e. the space between the bouton and the postsynaptic neurone, mediates the transfer of information from the pre- to the postsynaptic neurone. |

The shape and orientation of the dendritic tree of the neurone determines the amount and type of information that may reach the neurone. The course of its axon determines to which neurones this information may be passed on. The location of the neurone within the CNS determines to which major system the neurone belongs.

There are several hundred functionally different areas, i.e. groups of neurones, in the CNS. Based on their location, the shape of their dendritic tree and the course of their axon, several thousand types of neurones can be distinguished in the CNS.

Transmitters

  Neurotransmitters either excite or inhibit the postsynaptic neurone. The most prominent excitatory transmitter in the CNS is L-glutamate. The most prominent inhibitory transmitter in the CNS is GABA (gamma-amino butyric acid). Other "main" neurotransmitters are e.g. dopamine, serotonin, acetylcholine, noradrenaline and glycine. Each neurone uses only one of the main transmitters, and this transmitter is used at all synaptic boutons that originate from the neurone.
  One or more of the "minor" transmitters (there are several dozens of them - such as cholecystokinin, endogenous opioids, somatostatin, substance P) may be used together with a main transmitter.

  The molecular machinery which is needed to mediate the events occurring at excitatory synapses differs from that at inhibitory synapses. Differences in the morphological appearances of the synapses accompany the functional differences.

Receptors

  Usually there exists a multitude of receptors which are all sensitive to one particular neurotransmitter. Different receptors have different response properties, i.e. they allow the flux of different ions over the plasma membrane of the neurone or they may address different second messenger systems in the postsynaptic neurones. The precise reaction of the neurone to the various neurotransmitters released onto its plasma membrane at the synapses is determined by the types of receptors expressed by the neurone.

Suitable Slides
  sections of spinal cord - H&E, luxol fast blue/cresyl violet (LFB/CV), toluidine blue, Giemsa

Thoracic Spinal Cord, sheep - LFB/CV
Most neurones have a light, large nucleus with a distinct nucleolus. The cytoplasm of many neurones contains fairly large amounts of rough endoplasmatic reticulum, which may aggregate within the cytoplasm of the neurone to form Nissl-bodies. Nissl-bodies are prominent in motor neurones located in the ventral horn of the grey matter of the spinal cord. The neurites are difficult to identify in most types of stained sections. Only the most proximal segments of the primary dendrites are seen clearly. The size of the perikaryon depends on the level of activity of the neurone and the length of the processes which the neurone has to support. An usable range for the size of the perikaryon would be 15-50 µm, although much smaller and much larger neuronal perikarya exist.
Draw the spinal cord at low magnification and indicate the distribution of grey matter and white matter. Find a nice group of neurones in the grey matter and draw them at a high magnification. Finally, have a look at the white matter and identify the nuclei of glial cells. You will find similar nuclei also in the grey matter.

Thoracic spinal Cord - H&E, silver stain
These slides show the same major features as the LFB/CV stained sections. Try to identify neurones (primary dendrites, Nissl-bodies) and glial cell nuclei in the H&E stained section. Part of the cytoskeleton of neurones is (like the reticular connective tissue fibers) argyrophilic, i.e. they "love" silver and can be stained by silver stains. Aside from the neurones and their processes, fine fibrils are visible in the neuropil. Many of the fibrils represent axons travelling in the grey and white matter of the spinal cord.
It should not be necessary to prepare separate drawings for these slides. Make sure that you can identify the main structural features in all preparations.

### Glia

CNS tissue contains several types of non-neuronal, supporting cells, neuroglia.

Astrocytes (or astroglia) are star-shaped cells. Their processes are often in contact with a blood vessel (perivascular foot processes). Astrocytes provide physical and metabolic support to the neurones of the CNS. They participate in the maintenance of the composition of the extracellular fluid. Although not themselves directly involved in the process of communication between neurones, they may be involved in the removal of transmitters from synapses and the metabolism of transmitters. Astrocytes are also the scar-forming cells of the CNS. |

- Oligodendrocytes (or oligoglia) have fewer and shorter processes. Oligodendrocytes form myelin sheath around axons in the CNS and are the functional homologue of peripheral Schwann cells. Oligodendrocytes may, in contrast to Schwann cells in the periphery, form parts of the myelin sheath around several axons.
- Microglia are small cells with complex shapes. Microglia are, in contrast to neurones and the other types of glial cells, of mesodermal origin. They are derived from the cell line which also gives rise to monocytes, i.e. macrophage precursors which circulate in the blood stream. In the case of tissue damage, microglia differentiate into phagocytotic cells.

The ventricles of the brain and the central canal of the spinal cord are lined with ependymal cells. The cells are often cilated and form a simple cuboidal or low columnar epithelium. The lack of tight junctions between ependymal cells allows a free exchange between cerebrospinal fluid and nervous tissue. Ependymal cells can specialise into tanycytes, which are rarely ciliated and have long basal processes. Tanycytes form the ventricular lining over the few CNS regions in which the blood-brain barrier is incomplete. They do form tight junctions and control the exchange of substances between these regions and surrounding nervous tissue or cerebrospinal fluid. |

Many glial cells do express neurotransmitter receptors, but they do not form synapses with neurones. Neuronal activity may regulate glial function by a spillover of transmitter from synaptic sites, which are typically surrounded by fine processes of glial cells. Glial cells may also communicate with each other via GAP junctions.

Suitable Slides
  sections of the forebrain - toluidine blue, Giemsa, luxol fast blue/cresyl violet

Forebrain, Cortex, mouse - Giemsa and Forebrain, Hippocampus, mouse - Giemsa
Most glial cells are much smaller than neurones. Their nuclei are generally much smaller than neuronal nuclei, and they rarely contain an easily visible nucleolus. Other aspects of their morphology are variable. The glial cytoplasm is, if visible at all, very weakly stained. Different types of glial cells cannot be easily distinguished by their appearance in this type of preparation. Most of the small nuclei located in the white matter of the CNS, where they may form short rows, are likely to represent oligodendrocytes.
Browse through the sections at low or medium magnification and try to get a feeling for the structural diversity visible in the section available to you - parts of the section that look different from others are very likely to have different functions.
Find a spot that appears interesting (or least boring) to you and sketch its structure at low magnification. Choose a spot for high magnification, and draw some of the visible neurones and glial cells. Note the difference in the size and number of glial cells and neurones.

### Peripheral Nervous System (PNS)

The PNS comprises all nervous tissue outside the brain and spinal cord. It consists of groups of neurones (ganglion cells), called ganglia, feltworks of nerve fibres, called plexuses, and bundles of parallel nerve fibres that form the nerves and nerve roots. Nerve fibres, which originate from neurones within the CNS and pass out of the CNS in cranial and spinal nerves, are called efferent or motor fibers. Nerve fibres which originate from nerve cells outside the CNS but enter the CNS by way of the cranial or spinal nerves are called afferent or sensory nerve fibres.

The principal neurotransmitters in the PNS are acetylcholine and noradrenalin.

### Peripheral Nerves

Afferent, sensory fibres enter the spinal cord via the dorsal roots, while efferent, motor fibres leave the spinal cord via the ventral roots. Dorsal and ventral roots merge to form the spinal nerves, which consequently contain both sensory and motor fibres. As the spinal nerves travel into the periphery they split into branches and the exact composition of the nerve in terms of motor and sensory fibres is, of course, determined by the structures the nerve will innervate.

One nerve fibre consists of an axon and its nerve sheath. Each axon in the peripheral nervous system is surrounded by a sheath of Schwann cells. An individual Schwann cell may surround the axon for several hundred micrometers, and it may, in the case of unmyelinated nerve fibers, surround up to 30 separate axons. The axons are housed within infoldings of the Schwann cell cytoplasm and cell membrane, the mesaxon .

In the case of myelinated nerve fibres, Schwann cells form a sheath around one axon and surround this axon with several double layers (up to hundreds) of cell membrane. The myelin sheath formed by the Schwann cell insulates the axon, improves its ability to conduct and, thus, provides the basis for the fast saltatory transmission of impulses. Each Schwann cell forms a myelin segment, in which the cell nucleus is located approximately in the middle of the segment. The node of Ranvier is the place along the course of the axon where two myelin segments abut. |

Fibre types in peripheral nerves:

- Type A fibres (myelinated) are 4 - 20 µm in diameter and conduct impulses at high velocities (15 - 120 m per second). Examples: motor fibers, which innervate skeletal muscles, and sensory fibres.
- Type B fibres (myelinated) are 1 - 4 µm in diameter and conduct impulses with a velocity of 3 - 14 m per second. Example: preganglionic autonomic fibres.
- Type C fibres (unmyelinated) are 0.2 - 1 µm thick and conduct impulses at velocities ranging from 0.2 to 2 m per second. Examples: autonomic and sensory fibres.

Peripheral nerves contain a considerable amount of connective tissue. The entire nerve is surrounded by a thick layer of dense connective tissue, the epineurium. Nerve fibres are frequently grouped into distinct bundles, fascicles, within the nerve. The layer of connective tissue surrounding the individual bundles is called perineurium. The perineurium is formed by several layers of flattened cells, which maintain the appropriate microenvironment for the nerve fibres surrounded by them. The space between individual nerve fibres is filled by loose connective tissue, the endoneurium.

Fibrocytes, macrophages and mast cells are present in the endoneurium.
Nerves are richly supplied by intraneural blood vessels, which form numerous anastomoses. Arteries pass into the epineurium, form arteriolar networks in the perineurium and give off capillaries to the endoneurium.

Suitable Slides
  sections of peripheral nerve - H&E, osmium or plucked preparations of peripheral nerve - osmium

Peripheral Nerve, cat - osmium
Which structures can be recognized in peripheral nerves depends on the stain that has been used in the preparation. Osmium gives a black color to lipids. In osmium stained preparations it is possible to observe the myelin sheath surrounding the axon. A good impression of the different sizes of the nerve fibres may be obtained. The axon is usually not well preserved. It may only form a little dark spot somewhere within the dark ring which represents the myelin sheath. Lipid droplets in fat cells, which can be found in the connective tissue around nerves, stand out as large (much larger than the nerve fibres), round, homogeneously stained areas.
Draw the nerve at low magnification (you may include some of the stained lipid droplets) and a small section of it at high magnification.

Peripheral Nerve, rat - H&E
In longitudinal H&E stained sections it is possible to identify the axon running in its myelin sheath, nodes of Ranvier and Schwann cell nuclei. Components of the connective tissue elements, which accompany the nerve, should be visible and identifiable in both longitudinal and transverse sections. H&E stained and transversely cut preparations give a good picture of the axon in the middle of a ring-like structure (sometimes fussy), which represents the remains of the myelin sheath. Due to their small size and the lack of a myelin sheath, type C fibres are very difficult to detect in either osmium or H&E stains.
Draw part of the longitudinally and transversely sectioned nerve at high magnification. Include Schwann cell nuclei, myelin sheath, axons and, if possible, nodes of Ranvier.

### Ganglia

Ganglia are aggregations of nerve cells (ganglion cells) outside the CNS. Cranial nerve and dorsal root ganglia are surrounded by a connective tissue capsule, which is continuous with the dorsal root epi- and perineurium. Individual ganglion cells are surrounded by a layer of flattened satellite cells. Neurones in cranial nerve and dorsal root ganglia are pseudounipolar. They have a T-shaped process. The arms of the T represent branches of the neurite connecting the ganglion cell with the CNS (central branch) and the periphery (peripheral branch). Both branches function as one actively conducting axon, which transmits information from the periphery to the CNS. The stem is connected to the perikaryon of the ganglion cell and is the only process originating from it. Ganglion cells in dorsal root ganglia do not receive synapses. Their function is the trophic support of their neurites.

Early in development two processes emerge from the perikaryon of dorsal root ganglion cells, which merge in the course of development. These ganglion cells are therefore also called pseudounipolar neurones. Two processes emerge from the perikaryon of bipolar neurones. The majority of CNS neurones are multipolar, i.e. more than two processes (but only one axon) emerge from their perikaryon.

Autonomic ganglia do contain synapses, and the ganglion cells within them do have dendrites. They receive synapses from the first neurone of the two-neurone chain, which characterises most of the efferent connections of the autonomic nervous system. The second neurone is the ganglion cell itself. Some autonomic ganglia are embedded within the walls of the organs which they innervate (intramural ganglia - e.g. GIT and bladder).

Suitable Slides
  sections of dorsal root ganglia and autonomic ganglia - H&E, toluidine blue, Giemsa, luxol fast blue/cresyl/violet (LFB/CV)

Dorsal Root Ganglion, cat - H&E and Autonomic Ganglion - H&E
Ganglion cells will typically be several times larger than other cells in the ganglia. The perikaryon is very large and surrounds a large and light nucleus. Only the cells immediately surrounding the ganglion cells as one flattened layer are satellite cells. With a lot of luck you may see the process of a ganglion cell as it passes out of the capsule of satellite cells. Ganglion cells are of course in contact with other parts of the nervous system and with the peripheral tissues which they innervate. Consequently, nerve fibers will be visible close to or within the ganglion.
Sketch the appearance of the spinal ganglion section at low magnification. Draw a small section of the spinal ganglion and peripheral ganglion at high magnification. Label ganglion cells, satellite cells and, if visible, nerve fibres and connective tissue elements.

page content and construction: Lutz Slomianka
last updated: 9/01/04

" There is nothing captious about a man who has attained to this,
the one possible apotheosis in life, the Apotheosis of Stupidity;
and he begins to feel dignified and longævous like a tree. "

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