NERVE SYSTEM
Usinglectures(on theweb-page of the departmentpostedthe presentationtextandlectures), books,additional literatureand other sources, students must to preparethe following theoreticalquestions:
1. Spinal ganglion origin, development, general structure and functional meaning.
2. Morphological and functional peculiarities of spinal node sensory neurons and neuralgia compounds.
3. Peripheral nerve structure and meaning of connective tissue tunics.
4. Degeneration and regeneration of the nerve after the damage.
5. Simple and complex somatic reflex ark principal compounds.
6. Basic steps in the development of the nervous system.
7. The structural and functional characteristics of the spinal cord.
8. Comparison of gray matter and white matter in terms of: their location in the spinal cord and their predominant neuronal components (cell bodies, axons, dendrites).
9. Comparison of dura mater, arachnoid, and pia mater in terms of their tissue type and the presence of blood vessels.
10. Description of the blood-brain barrier in terms of its structural correlates and its function.
11. Description of the source, composition and circulation of the cerebrospinal fluid.
12. Cerebellum: general structure and function.
13. Layers of the gray matter cortex, characteristic of each neuron, which one can find in the cortex.
14. Afferent and efferent tracks of the cerebellum.
15. Main structural peculiarities of the cerebellum gray matter.
16. The structure and role of the reticular formation tube.
17. Large hemispheres.
18. Cytoarchitecture and myeloarchitecture of cerebral cortex.
19. Morphofunctional characteristic of cerebral cortex neurons.
20. The agranular and granular types of cerebral cortex.
21. Describe the blood – brain barrier in terms of its structural correlates and its function.
22. Autonomic nervous system general morphofunctional characteristic. Classification.
23. Nervous system sympathetic portion. Disposition of the central nuclei and peripheral (extramural) ganglia.
24. Types of the autonomic ganglia neurons.
25. Structural particularities of the pre- and postganglionic fibers.
26. Parasympathetic portion of the autonomic nervous system. Central nuclei disposition and intramural ganglia particularities.
27. Autonomic reflectory arch specific feature, its morphologic compartments.
Nerve system anatomically is divided into the central nervous system (CNS), comprising the brain and spinal cord, and the peripheral nervous system (PNS), which constitutes all nervous tissue outside the CNS (peripheral nerves, ganglia, plexus and nervous endings).
The peripheral nervous system, or PNS, is part of the nervous system, and consists of the nerves and neurons that reside or extend outside the central nervous system (the brain and spinal cord) to serve the limbs and organs, for example. Unlike the central nervous system, however, the PNS is not protected by bone or the blood-brain barrier, leaving it exposed to toxins and mechanical injuries. The peripheral nervous system is divided into the somatic nervous system and the autonomic nervous system.
Histologically, however, the entire nervous system merely consists of variations in the arrangement of neurons and their supporting structures.
NERVOUS SYSTEM ORIGIN
Nerve system originate of nerve tube and ganglious lamella. The brain and sense organs are developing from the cranial portion of nerve tube. Middle part of nerve tube and ganglionic plate give rise to spinal cord, dorsal-root ganglia (spinal ganglia), autonomic ganglia and chromaffin tissue of human body. The cells mass especially quiqly increases in the lateral part of nerve tube, whereas dorsal and ventral portions are not inlarged and have ependymal features. At this stage three zones can be recognized in the wall of nerve tube: ependyma, which covers the spinal channel, mantial layer and marginal zone. The innermost layer contains the precursors of glial ependymal cells. Population of middle zone includes two type of cells: neuroblasts and spongyoblasts, whichgive rise accordingly to nerve cells and glyal ones (astrocytes and oligodendrocytes). Later grey matter of spinal cord is developing from mantial zone and white matter from outer one.
The development of dorsal-root ganglia and peripheral autonomic ganglia begins at the same time. Ganglionic plate gives the sources for their origin – neuroblasts and glioblasts, which differentiate into neurons and mantial cells of spinal ganglia. Some cells migrate peripherally and there produce autonomic ganglia and chromaffin tissue.
SPINAL CORD
Spinal cord is long cylindrical structure, which elongates from the brain down to the lumbar part, in which it is continuing into caudaequina.
In cross sections of the spinal cord, white matter is peripheral and gray matter is central, assuming the shape of an H. In the horizontal bar of this H is an opening, the central canal, which is a remnant of the lumen of the embryonic neural tube. It is lined by ependymal cells. The gray matter of the legs of the H forms the anterior horns. These contain motor neurons, arranged in 5 nuclei, whose axons make up the ventral roots of the spinal nerves. Gray matter also forms the posterior horns (the arms of the H), which receive sensory fibers from neurons in the spinal ganglia (dorsal roots). Here are two nuclei: nucleus thoracicus and nucleus proprius.
The intermediate horns are better prominent in the thorathic and lumbar part of spinal cord and contain lateral and medial nuclei. The first ones belong to the sympathetic nerve system: they are the centers of it.
Cross section through the spinal cord.
Spinal cord neurons mainly are large and multipolar, especially in the anterior horns, where large motor neurons are found.
Nerve cells of spinal cord are classifying in special way: radicular, funicular and inner cells. Radicular cells are found in the anterior horns nuclei and intermediate lateral one. Axons of these cells move outside from spinal cord forming the anterior radix. Funicular cells of other nuclei pass their axons to the gray matter in which they form the ascendant funiculi of white matter (passways of the spinal cord). Inner cells are present in all the nuclei, their axons connect the neurons in gray matter.
Cross section of the spinal cord in the transition between gray matter (below) and white matter (above). Note the neuronal bodies and abundant cell processes in the gray matter, whereas the white matter consists mainly of nerve fibers whose myelin sheath was dissolved by the histologic procedure. PT stain. Medium magnification.
A group of large multipolar neurons, as found in the gray matter of the anterior horn. Cell nuclei are pale (or vesicular) and round and contain a large amount of Nissl substance (RER). The smallest nuclei in the field belong to glial cells. In an area like this, glia play a supportive and nutritive role. They take the place of connective tissue within the central nervous system (i.e., the brain and spinal cord).
A large, multipolar, motor neuron of the anterior horn, seen whole, with all its processes stretched out in a spinal cord smear. Notice the dark clumps of Nissl substance in the cytoplasm. The axon cannot be identified with certainty in this particular view. Neuroglial nuclei surround the neuron. Of these small nuclei, the lightest ones, showing small clumps of chromatin, belong to astrocytes; any dark, round ones (such as the one in the upper right corner) belong to oligodendroglia; and any dark, thin, cigar-shaped ones to microglia (see possible one just to right of the neuron).
Section of the gray matter of the spinal cord showing several motor neurons with their basophilic bodies (Nissl bodies). Nucleoli are seen in some nuclei. The neurons are surrounded by a mesh of neuronal and glial processes. PT stain. Medium magnification.
Section of spinal cord gray matter. The meshwork of cell neuron and glial processes appears distinctly. The small nuclei are from glia cells. Note that these cells are more numerous thaeurons. H&E stain. Medium magnification.
Glial nuclei seen in white matter of the cord, cut so that nerve processes are seen running longitudinally. Most of these are round, dark oligodendroglial nuclei; these are the cells responsible for the myelin wrapping of axons of the central nervous system.
Silvered preparation of astrocytes, showing their many fine cytoplasmic processes. Note their close relationship to capillaries, the heavy black structures. Since astrocytes touch both capillaries and neurons, they are thought to play an important intermediary role in the nutrition and metabolism of neurons.
MENINGES
The central nervous system is protected by the skull and the vertebral column. It is also encased in membranes of connective tissue called the meninges. Starting with the outermost layer, the meninges are the dura mater, arachnoid, and pia mater. The arachnoid and the pia mater are linked together and are often considered a single membrane called the pia-arachnoid.
Dura Mater
The dura mater is the external layer (meninx) and is composed of dense connective tissue. The dura mater that envelops the spinal cord is separated from the periosteum of the vertebrae by the epidural space, which contains thin-walled veins, loose connective tissue, and adipose tissue.
The dura mater is always separated from the arachnoid by the thin subdural space. The internal surface of all dura mater, as well as its external surface in the spinal cord, is covered by simple squamous epithelium of mesenchymal origin.
Arachnoid
The arachnoid (Gr. arachnoeides, cobweb-like) has two components: a layer in contact with the dura mater, and a system of trabeculae connecting the layer with the pia mater. The cavities between the trabeculae form the subarachnoid space, which is filled with cerebrospinal fluid and is completely separated from the subdural space. This space forms a hydraulic cushion that protects the central nervous system from trauma. The subarachnoid space communicates with the ventricles of the brain.
The arachnoid is composed of connective tissue devoid of blood vessels. Its surfaces are covered by the same type of simple squamous epithelium that covers the dura mater. Since the arachnoid has fewer trabeculae in the spinal cord, it can be more cleanly distinguished from the pia mater in that area.
In some areas, the arachnoid perforates the dura mater, forming protrusions that terminate in venous sinuses in the dura mater. These protrusions, which are covered by endothelial cells of the veins, are called arachnoid villi. Their function is to reabsorb cerebrospinal fluid into the blood of the venous sinuses.
Pia Mater
The pia mater is a loose connective tissue containing many blood vessels. Although it is located quite close to the nerve tissue, it is not in contact with nerve cells or fibers. Between the pia mater and the neural elements is a thin layer of neuroglial processes, adhering firmly to the pia mater and forming a physical barrier at the periphery of the central nervous system. This barrier separates the central nervous system from the cerebrospinal fluid.
The pia mater follows all the irregularities of the surface of the central nervous system and penetrates it to some extent along with the blood vessels. Pia mater is covered by squamous cells of mesenchymal origin.
Blood vessels penetrate the central nervous system through tunnels covered by pia mater – the perivascular spaces. The pia mater disappears before the blood vessels are transformed into capillaries. In the central nervous system, the blood capillaries are completely covered by expansions of the neuroglial cell processes.
The structure of the meninges, with the superposition of pia mater, arachnoid, and dura mater. Astrocytes form a 3-dimensional net around the neurons (not shown). Note that the footlike processes of the astrocytes form a continuous layer that involves the blood vessels that contribute to the blood-brain barrier.
Blood-Brain Barrier
The blood-brain barrier is a functional barrier that prevents the passage of some substances, such as antibiotics and chemical and bacterial toxic matter, from the blood to nerve tissue. It is present in central nerve system.
The blood-brain barrier results from the reduced permeability that is a property of blood capillaries of nerve tissue. Occluding junctions, who provide continuity between the endothelial cells of these capillaries, represent the main structural component of the barrier. The cytoplasm of these endothelial cells does not have the fenestrations found in many other locations, and very few pinocytotic vesicles are observed. The expansions of neuroglial cell processes that envelop the capillaries are partly responsible for their low permeability.
Blood-brain barrier of spinal cord consists of:
Capillary wall
1. Continuous endothelium
2. Continuous basement membrane
3. Glial sheath (foot processes of astrocytes)
HOROID PLEXUS & CEREBROSPINAL FLUID
The choroid plexus consists of invaginated folds of pia mater that penetrate the interior of the ventricles. It is found in the roofs of the third and fourth ventricles and in part in the walls of the lateral ventricles. It is a vascular structure made up of dilated fenestrated capillaries.
The choroid plexus is composed of loose connective tissue of the pia mater, covered by a simple cuboidal or low columnar epithelium that has the cytologic characteristics of ion-transporting cells.
The main function of the choroid plexus is to elaborate cerebrospinal fluid, which contains only a small amount of solids and completely fills the ventricles, central canal of the spinal cord, subarachnoid space, and perivascular space. Cerebrospinal fluid is important for the metabolism of the central nervous system and acts as a protective device.
Cerebrospinal fluid is very low in protein content. A few desquamated cells and two to five lymphocytes per milliliter are also present. Cerebrospinal fluid circulates through the ventricles, from which it passes into the subarachnoid space. There, arachnoid villi provide the main pathway for absorption of cerebrospinal fluid into the venous circulation. There are no lymphatic vessels ierve tissue.
A decrease in the absorption of cerebrospinal fluid or a blockage of outflow from the ventricles results in the condition known as hydrocephalus (Or. hydro, water, + kephale, head), which promotes a progressive enlargement of the head followed by mental impairment and muscular weakness.
Photomicrograph of choroid plexus section. The choroid plexus presents a core of loose connective tissue rich in blood capillaries (BC) covered by a simple cubic epithelium (arrowhead). H&E stain. Medium magnification.
PERIPHERAL NERVOUS SYSTEM
The main components of the peripheral nervous system are the nerves, ganglia, plexus and nerve endings. Nerves are bundles of nerve fibers surrounded by a series of connective tissue sheaths.
NERVE FIBERS
Nerve fibers consist of axons enveloped by a special sheath derived from cells of ectodermal origin. Groups of nerve fibers constitute the tracts of the brain, spinal cord, and peripheral nerves. Nerve fibers exhibit differences in their enveloping sheaths, related to whether the fibers are part of the central or the peripheral nervous system.
Most axons in adult nerve tissue are covered by single or multiple folds of a sheath cell. In peripheral nerve fibers, the sheath cell is the Schwann cell, and in central nerve fibers it is the oligodcndrocyte. Axons of small diameter are usually unmyelinated nerve fibers. Progressively thicker axons are generally sheathed by increasingly numerous concentric wrappings of the enveloping cell, forming the myelin sheaths. These fibers are known as myelinated nerve fibers.
Myelinated Fibers
In myelinated fibers of the peripheral nervous system, the plasmalemma of the covering Schwann cell winds and wraps around the axon. The layers of membranes of the sheath cell unite and form myelin, a lipoprotein complex whose lipid component can be partly removed by standard histologic procedures.
Myelin consists of many layers of modified cell membranes. These membranes have a higher proportion of lipids than do other cell membranes. Central nervous system myelin contains two major proteins: myelin basic protein and proteolipid protein. Several human demyelinating diseases are due to an insufficiency or lack of one or both of these proteins.
Each axon is surrounded by myelin formed by a sequential series of Schwann cells. The myelin sheath shows gaps along its path called the nodes of Ranvier; these represent the spaces between adjacent Schwann cells along the length of the axon. Interdigitating processes of Schwann cells partially cover the node. The distance between two nodes is called an internode and consists of one Schwann cell. The length of the inter-node varies between 1 and
There are no Schwann cells in the central nervous system; there, the myelin sheath is formed by the processes of the oligodendrocytes. Oligodendrocytes differ from Schwann cells in that different branches of one cell can envelop segments of several axons.
Myelin sheath of the central nervous system. The same oligodendrocyte forms myelin sheaths for several (3–50) nerve fibers. In the central nervous system, processes of other cells sometimes cover the nodes of Ranvier, or there is considerable extracellular space (ES) at that point. The axolemma shows a thickening where the cell membrane of the oligodendrocyte comes into contact with it. This limits the diffusion of materials into the periaxonal space between the axon and the myelin sheath. At upper left is a surface view of the cell body of an oligodendrocyte. Cyt, cytoplasm of the oligodendrocyte.
Drawing of relation of an oligodendrocyte to a neuronal axon in the CNS, as seen in E.M. An extension of cell cytoplasm wraps around the axon, making a multi-layered myelin sheath. Ordinarily there is one oligodendrocyte between two successive nodes of Ranvier. Notice that the cell has other cytoplasmic extensions up above, which are free to as sociate with other axons. This same principle of lamellated (layered) myelin sheath formation holds true also for Schwann cells and peripheral nerves. One difference, however, is that a Schwann cell is believed to wrap only one axon instead of several. Notice that the plasma membrane of the axon is bare at the point of the node; this allows for rapid saltatory conduction as the impulse jumps from node to node to node.
Unmyelinated Fibers
In both the central and peripheral nervous systems, not all axons are sheathed in myelin. In the peripheral system, all unmyelinated axons are enveloped within simple clefts of the Schwann cells. Unlike their association with individual myelinated axons, each Schwann cell can sheathe many unmyelinated axons. Unmyelinated nerve fibers do not have nodes of Ranvier, because abutting Schwann cells are united to form a continuous sheath.
The central nervous system is rich in unmyelinated axons; unlike those in the peripheral system, these axons are not sheathed. In the brain and spinal cord, unmyelinated axonal processes run free among the other neuronal and glial processes.
NERVES
In the peripheral nervous system, the nerve fibers are grouped in bundles to form the nerves. Except for a few very thierves made up of unmyelinated fibers, nerves have a whitish, homogeneous, glistening appearance because of their myelin and collagen content. A nerve is an enclosed, cable-like bundle of axons (the long, slender projection of a neuron). Neurons are sometimes called nerve cells, though this term is technically imprecise since many neurons do not form nerves, and nerves also include the glial cells that ensheath the axons in myelin.
Nerves are part of the peripheral nervous system. Afferent nerves convey sensory signals to the central nervous system, for example from skin or organs, while efferent nerves conduct stimulatory signals from the central nervous system to the musclesand glands. Afferent and efferent nerves are often arranged together, forming mixed nerves.
Each peripheral nerve is covered externally by a dense sheath of connective tissue, the epineurium. Underlying this is a layer of flat cells forming a complete sleeve, the perineurium. Perineurial septa extend into the nerve and subdivide it into several bundles of fibres. Surrounding each such fibre is the endoneurial sheath. This is a tube which extends, unbroken, from the surface of the spinal cord to the level at which the axon synapses with its muscle fibres or ends in sensory endings. The endoneurial sheath consists of an inner sleeve of material called the glycocalyx and an outer, delicate, meshwork of collagen fibres. Peripheral nerves are richly supplied with blood.
Most nerves connect to the central nervous system through the spinal cord. The twelve cranial nerves, however, connect directly to parts of the brain. Spinal nerves are given letter-number combinations according to the vertebrathrough which they connect to the spinal column. Cranial nerves are assigned numbers, usually expressed as Romaumerals from I to XII. In addition, most nerves and major branches of nerves have descriptive names. Inside the central nervous system, bundles of axons are termed tracts rather thaerves.
The signals that nerves carry, sometimes called nerve impulses, are also known as action potentials: rapidly (up to 120 m/s) traveling electrical waves, which begin typically in the cell body of a neuron and propagate rapidly down the axon to its tip or “terminus.” The signals cross over from the terminus to the adjacent neurotransmitter receptor through a gap called the synapse. Motor neuronsinnervate or activate muscles groups. The nerve system runs through the spinal cord.
Cross sections of two small nerves with a thin covering layer. Note the Schwann cell nuclei (arrowheads) and the axons (arrows). PT stain. Medium magnification.
Electron micrograph of a peripheral nerve containing both myelinated (M) and unmyelinated (U) nerve fibers. The reticular fibers (RF) seen in cross section belong to the endoneurium. Near the center of the figure is a Schwann cell nucleus (S). The perineurial cells (P [over a nucleus], arrows) form a barrier that controls access of materials to nerve tissue. x30,000. Inset: Part of an axon, where numerous neurofilaments and microtubules are seen in cross section. x60,000.
EM of myelinated axons of peripheral nerve. The dark, many-layered myelin sheaths surround pale axons. At the upper edge of the picture is a nucleus of a Schwann cell, with its outer rim of cytoplasm continuous with the outer rim of the myelin sheath of the axon in the left corner. (Remember that non-myelinated axons are also closely related to Schwann cells, but the Schwann cells form no layered wrappings around them. Note, too, that one Schwann cell can be related to several axons when these are non-myelinated.)
Nerves have an external fibrous coat of dense connective tissue called epineurium, which also fills the space between the bundles of nerve fibers. Each bundle is surrounded by the perineurium, a sleeve formed by layers of flattened epithelium-like cells. The cells of each layer of the perineurial sleeve are joined at their edges by tight junctions, ah arrangement that makes the perineurium a barrier to the passage of most macromolecules and has the important function of protecting the nerve fibers from aggression. Within the perineurial sheath run the Schwann cell-sheathed axons and their enveloping connective tissue, the endoneurium. The endoneurium consists of a thin layer of reticular fibers. Endoneurial reticular fibers are produced by Schwann cells.
The nerves establish communication between brain and spinal cord centers and the sense organs and effectors (muscles, glands, etc). They possess afferent and efferent fibers to and from the central nervous system. Afferent fibers carry the information obtained from the interior of the body and the environment to the central nervous system. Efferent fibers carry impulses from the central nervous system to the effector organs commanded by these centers. Nerves possessing only sensory fibers are called sensory nerves; those composed only of fibers carrying impulses to the effectors are called motor nerves. Most nerves have both sensory and motor fibers and are called mixed nerves; these nerves have both myelinated and unmyelinated axons.
Electron micrograph of a cross section through a nerve, showing the epineurium, the perineurium, and the endoneurium. The epineurium is a dense connective tissue rich in collagen fibers (
Cross-cuts of small peripheral nerve bundles as seen in ordinary tissue sections. The processes have a typically wavy appearance.
Cross section of a thick nerve stained to show its collagenous components. Picrosirius–polarized light stain. Medium magnification
A higher magnification of one bundle of peripheral nerve, showing cross-cuts of individual processes. The ones in the center are the truest cut; those on either side are tangentially cut. The best ones show a darker axon in the center of the fiber, surrounded by a paler myelin sheath. Remember that some of these fibers are axons of motor neurons, whose cell bodies are in the anterior horn of the spinal cord, while other fibers are dendrites of the pseudounipolar sensory cells of the spinal ganglion. This is the one instance where functional dendrites (i.e., processes coming into the cell body) are structurallv like axons with myelin sheaths. The dense sheath at the outer edge of the bundle here is perineurium. The lines of pink surrounding each process represent endoneurium.
Higher magnification of longitudinally cut nerve, showing a clear node of Ranvier in the center of the field. Note that the axon is continuous through the node. Notice also the “foamy”, grainy appearance of the myelin sheaths; this represents the proteinaceous material of the cell membrane wrappings of the sheath, often called “neurokeratin” although this is a misnomer. The lipid portion of the membranes has been dissolved out during tissue fixation.
Detail of node of Ranvier, with axon continuing through it. Axons stain deep pink. Myelin is pale because the lipid material disolves out. The dark strands of proteieurokeratin give the “foamy” look to the myelin in light microscopy. Nuclei, seen here near the bottom of the picture, lie betweeerve processes and belong to either Schwann cells or endoneurial connective tissue cells (such as fibroblasts).
Detail of a motor nerve ending upon a skeletal muscle cell (voluntary muscle). The axon terminal is highly branched to form an oval motor end plate. The cell body which sends out this axon is a multipolar motor neuron, such as those in the anterior horn of the spinal cord.
Electronmicrograph of axo-muscular synapse in skeletal muscle. X 33000.
Diagram of motor end plate (myoneural junction) as seen with electron microscopy. This drawing shows a detail of one knob of an end plate as it rests in a trough on the surface of a muscle cell. The “subneural clefts” labelled here are also called “gutters” in the sarcolemmal membrane. The label “glycoprotein” indicates the position of the basal lamina of the muscle cell.
EM detail of neuro-neural synapse in the brain or spinal cord. The axon terminal contains many seed-like synpatic vesicles containing transmitter substances. The intercellular cleft between the axon and the contacted dendrite can be seen. Just below the dendritic cell membrane is a dark, filamentous post-synaptic density. Other profiles in this field, most of them very irregular in outline, belong to both neuronal processes and glial processes. There is one large and one small mitochondrion just left of the synaptic vesicles.
Muscle spindle – a specialized sensory receptor for muscle stretch and position sense, as related particularly to unconscious maintenance of skeletal muscle tone and proper balance of postural muscle activity. The spindle is the encapsulated group of muscle fibers lying in the center of the field of regular skeletal muscle fibers, all cut in cross-section. The sensory nerve endings themselves (not visible here) wrap around the muscle fibers within the spindle. Such endings relay sensory information along dendrites within peripheral nerves, back to pseudounipolar cell bodies in a spinal ganglion, and thence to the spinal cord.
Pacinian corpuscle – another specialized sensory ending, this time for deep pressure. This particular view is from a whole mount of mesentery, so you are seeing the corpuscle three-dimensionally. They are also found in subcutaneous tissue, deep to skin. Notice the onion-like layers of specialized connective tissue surrounding a dark pink dendritic terminal. Again, the cell body for this dendrite lies in a spinal ganglion, and the axon of that same cell then proceeds into the spinal cord.
Ruffini’s body (mechanoreceptor)
Bulb of Crause (thermoreceptor)
Meissner’s body (scheme)
GANGLIA
Ganglia are ovoid structures containing neuronal cell bodies and glial cells supported by connective tissue. Because they serve as relay stations to transmit nerve impulses, one nerve enters and another exits from each ganglion. The direction of the nerve impulse determines whether the ganglion will be a sensory or an autonomic ganglion.
Sensory Ganglia
Sensory ganglia receive afferent impulses that go to the central nervous system. Two types of sensory ganglia exist. Some are associated with cranial nerves (cranial ganglia); others are associated with the dorsal root of the spinal nerves and are called spinal ganglia. The latter comprise large neuronal cell bodies with prominent fine Nissl bodies surrounded by abundant small glial cells called satellite cells.
This slide is an overview of one half of a transverse section of the spinal cord, along with its ventral and dorsal roots and a spinal ganglion. At the extreme left (which is close to the midline of the cord) notice a small central canal lined by a dark layer of ependymal this contains cerebrospinal fluid in life. Above the canal lies the narrow slit of the posterior median sulcus, and below the canal is a wider, bulging separation called the anterior median fissure. Lateral to all these spaces lies the gray matter of the cord (quite pink here), where neuronal cell bodies lie. Surrounding the gray matter is a layer of white matter, consisting of nerve cell processes, all of them axons, running up or down the length of the cord and therefore cut in cross-section here. Outside the cord, to the right, lies a mass of nerve cell bodies, the spinal ganglion, interrupting the course of the dorsal root. Below the ganglion lies the ventral root. Surrounding the entire complex is a well-defined, pink band of dura mater which consists of dense collagenous connective tissue. The wedge of delicate areolar connective tissue at the bottom of the anterior median fissure is the arachnoid; note the round cross-cut of a blood vessel lying in it. The pia mater, invisible here, is an extremely thin connective tissue layer immediately investing the spinal cord.
A connective tissue framework and capsule support the ganglion cells. The neurons of these ganglia are pseudounipolar and relay information from the ganglion’s nerve endings to the gray matter of the spinal cord via synapses with local neurons.
Silver-impregnated sensory ganglion consisting of pseudounipolar neurons.Medium magnification.
Spinal ganglion in Mallory connective tissue stain. The pseudounipolar cells are in characteristic groups or clumps, separated by bands of nerve processes. The processes might be either dendrites arriving from the body periphery or axons proceeding on to the spinal cord. Either way, the cell bodies or origin for the processes lie within the spinal ganglion and are sensory neurons. The dark blue sheath outside the ganglion is the dense collagenous connective tissue dura mater.
Detail of pseudounipolar spinal ganglion each one encapsulated by a layer of small satellite cells. Bright blue material is the supportive connective tissue, which is directly continuous with the endoneurium surrounding the individual nerve processes entering and leaving the ganglion. Remember that connective tissue is the supportive tissue of the peripheral nervous system.
Higher power of spinal ganglion stained with H&E. Satellite cell capsules are clear. The large neuron in the center of the field has a pale axon hillock where the seemingly single process enters and leaves. In such a pseudounipolar cell, the incoming dendrite and outgoing axon seem to be related to the cell body by means of a single “stalk”. The paleness of the hillock is due to the absence of RER (Nissl substance) in this area.
DEGENERATION & REGENERATION OF NERVE TISSUE
Although it has been shown that neurons can divide in the brain of adult birds, mammaliaeurons usually do not divide, and their degeneration represents a permanent loss. Neuronal processes in the central nervous system arc, within very narrow limits, replaceable by growth through the synthetic activity of their perikaryons.
Peripheral nerve fibers can also regenerate if their perikaryons are not destroyed.
Death of a nerve cell is limited to its perikaryon and processes. The neurons functionally connected to the dead neuron do not die, except for those with only one link. In this latter instance, the isolated neuron undergoes transneuronal degeneration.
In contrast to nerve cells, neuroglia of the central nervous system – and Schwann cells and ganglionic satellite cells of the peripheral nervous system – are able to divide by mitosis. Spaces in the central nervous system left by nerve cells lost by disease or injury are invaded by neuroglia.
Since nerves are widely distributed throughout the body, they are often injured. When a nerve axon is transected, degenerative changes take place, followed by a reparative phase.
In a wounded nerve fiber, it is important to distinguish the changes occurring in the proximal segment from those in the distal segment. The proximal segment maintains its continuity with the trophic center (perikaryon) and frequently regenerates. The distal segment, separated from the nerve cell body, degenerates.
Axonal injury causes several changes in the perikaryon: chromatolysis, i.e., dissolution of Nissl substances with a consequent decrease in cytoplasmic basophilia; an increase in the volume of the perikaryon; and migration of the nucleus to a peripheral position in the perikaryon. The proximal segment of the axon degenerates close to the wound for a short distance, but growth starts as soon as debris is removed by macrophages. Macrophages produce interleukin-1, which stimulates Schwann cells to secrete substances that promote nerve growth.
In the nerve stub distal to the injury, both the axon (now separated from its trophic center) and the myelin sheath degenerate completely, and their remnants, excluding their connective tissue and perineurial sheaths, are removed by macrophages. While these regressive changes take place, Schwann cells proliferate within the remaining connective tissue sleeve, giving rise to solid cellular columns. These rows of Schwann cells serve as guides to the sprouting axons formed during the reparative phase.
After the regressive changes, the proximal segment of the axon grows and branches, forming several filaments that progress in the direction of the columns of Schwann cells. Only fibers that penetrate these Schwann cell columns will continue to grow and reach an effector organ.
When there is an extensive gap between the distal and proximal segments, or when the distal segment disappears altogether (as in the case of amputation of a limb), the newly growerve fibers may form a swelling, or neuroma, that can be the source of spontaneous pain.
Regeneration is functionally efficient only when the fibers and the columns of Schwann cells are directed to the correct place. The possibility is good, however, since each regenerating fiber gives origin to several processes, and each column of Schwann cells receives processes from several regenerating fibers. In an injured mixed nerve, however, if regenerating sensory fibers grow into columns connected to motor end-plates that were occupied by motor fibers, the function of the muscle will not be reestablished.
Damage to nerves can be caused by physical injury, swelling (e.g. carpal tunnel syndrome), autoimmune diseases (e.g. Guillain-Barré syndrome), infection (neuritis), diabetes, or failure of the blood vessels surrounding the nerve. Pinched nerves occur when pressure is placed on a nerve, usually from swelling due to an injury or pregnancy. Nerve damage or pinched nerves are usually accompanied by pain, numbness, weakness, or paralysis. Patients may feel these symptoms in areas far from the actual site of damage, a phenomenon called referred pain. Referred pain occurs because when a nerve is damaged, signaling is defective from all parts of the area which the nerve receives input, not just the site of the damage.
Neurologists usually diagnose disorders of the nerves by a physical examination, including the testing of reflexes, walking and other directed movements, muscle weakness, proprioception, and the sense of touch. This initial exam can be followed with tests such as nerve conduction study and electromyography (EMG).
Plasticity of nerve tissue
Despite its general stability, the nervous system exhibits some plasticity in adults. Plasticity is very high during embryonic development, when an excess of nerve cells is formed and the ones that do not establish correct synapses with other neurons are eliminated. Several studies made in adult mammals have shown that, after an injury, the neuronal circuits may be reorganized by the growth of neuronal processes, forming new synapses to replace the ones lost by injury. Thus, new communications arc established with some degree of functional recovery. This property of nerve tissue is known as neuronal plasticity. The regenerative processes in the nervous system are controlled by several growth factors produced by neurons, glial cells, Schwann cells, and target cells. These growth factors form a family of molecules called neurotrophins.
Tumors of the Nervous System
Virtually all cells of the nerve tissue generate tumors. Glial cells produce gliomas. immature nerve cells produce medulloblastomas, and Schwann cells produce schwannumas. Because adult neurons do not divide, they do not produce tumors.
Cerebellum.Hemispheres of the brain.
NERVous SYSTEM
The location and degree of development of the human brain is the result of millions of years of evolution. Both functionally and structurally the primary centers for control and regulation of all nervous system function have become centralized in a process called encephalization. In lower animals the spinal cord has a great degree in independence from the brain, while in the human spinal cord function is directly under the regulation of the brain. The functional development of the brain distinguishes humans from lower animals, but anatomic differences are not as apparent. If we compare our brain with that of other primates, we can find the same basic structures in both; however, upon closer study, we find there are marked differences in degrees of development. This developmental change is in the form of more extensive neuron tracts in the human brain and a much greater degree of synaptic connections betweeeuron cell bodies.
Nervous system is a special highly organized system (which consists of nervous tissue and connective) – intercommunicating network of neurons that constitute most sensory receptors, the conducting pathways and the sites of integration and analysis. The function of the nervous system is to receive stimuli from both internal and external environments, to analyze and integrate them, to produce appropriate coordinated responses in various effector organs.
Anatomically it is divided into the central nervous system (CNS), comprising the brain and spinal cord, and the peripheral nervous system (PNS), which constitutes all nervous tissue outside the CNS (peripheral nerves, ganglia, plexus and nervous endings).
The nervous system of a human coordinates the activity of the muscles, monitors the organs, constructs and also stops input from the senses, and initiates actions. Prominent participants in a nervous system include neurons and nerves, which play roles in such coordination. All parts of the nervous system are made of nervous tissue.
The brain has three main parts that interact with the nervous system: the cerebrum, the cerebellum, and the medulla oblongata. Examples of the cerebrum’s tasks include high-order thinking and learning, while the cerebellum manages learned automatic bodily functions, including walking, jumping, and running. The medulla processes simple body functions, such as breathing and digestion
The spinal cord is the area where reflexes are made. Split-second decisions do not go back to the brain and then back to the organ or body part. This would take too long and the nerve impulse would arrive too late to prevent the stimulus from becoming reality. For instance, if a ball was thrown at an individual’s head, the reflex to move out of the way would come from the spine, not the brain, increasing reaction time. The spine is also the “highway” which passes orders from the brain to motor nerves.
The general functional organization of the central and peripheral nervous systems.
Functionally the nervous system is divided into the somatic portion that is involved in voluntary functions and autonomic one, which exerts control over many involuntary functions.
Histologically, however, the entire nervous system merely consists of variations in the arrangement of neurons and their supporting structures.
NERVOUS SYSTEM ORIGIN
Neurulation is a part of organogenesis in vertebrateembryos. This mean the formation of nerve tube and begins at the stage of late gastrulation (14-17 days of embryogenesis). Steps of neurulation include the formation of the dorsal nerve cord,and the eventual formation of the central nervous system. The process begins when the notochordinduces the formation of the central nervous system (CNS) by signaling the ectoderm germ layerabove it to form the thick and flat neural plate. The neural plate folds in upon itself to form the neural tube, which will later differentiate into the spinal cordand the brain, eventually forming the central nervous system.
Different portions of the neural tube form by two different processes, called primary and secondary neurulation, in different species.
In primary neurulation, the neural plate creases inward until the edges come in contact and fuse.
In secondary neurulation, the tube forms by hollowing out of the interior of a solid precursor.
Transverse sections that show the progression of the neural plate to the neural groove from bottom to top.
Primary neurulation. Induction
Primary neurulation occurs in response to soluble growth factors secreted by the notochord. Ectodermal cells are induced to form neuroectoderm from a variety of signals. Ectoderm sends and receives signals of BMP4 (bone morphogenic protein) and cells which receive BMP4 signal develop into epidermis. The inhibitory signals chordin, noggin and follistatin are needed to form neural plate. These inhibitory signals are created and emitted by the notochord. Cells which do not receive BMP4 signaling due to the effects of the inhibitory signals will develop into the anterior neuroectoderm cells of the neural plate. Cells which receive FGF (fibroblast growth factor) in addition to the inhibitory signals form posterior neural plate cells.
The cells of the neural plate are signaled to become high-columnar and can be identified through microscopy as different from the surrounding epiblastic ectoderm. The cells move laterally and away from the central axis and change into a truncated pyramid shape. This pyramid shape is achieved through tubulin and actin in the apical portion of the cell which constricts as they move. The variation in cell shapes is partially determined by the location of the nucleus within the cell, causing bulging in areas of the cells forcing the height and shape of the cell to change.
The process of the flat neural plate folding into the cylindrical neural tube is termed primary neurulation. As a result of the cellular shape changes, the neural plate forms the medial hinge point (MHP). The expanding epidermis puts pressure on the MHP and causes the neural plate to fold resulting in neural folds and the creation of the neural groove. The neural folds form dorsolateral hinge points (DLHP) and pressure on this hinge causes the neural folds to meet and fuse at the midline. The fusion requires the regulation of cell adhesion molecules. The neural plate switches from E-cadherin expression to N-cadherin and N-CAM expression to recognize each other as the same tissue and close the tube. This change in expression stops the binding of the neural tube to the epidermis.
The notochord plays an integral role in the development of the neural tube. Prior to neurulation, during the migration of epiblastic endoderm cells towards the hypoblastic endoderm, the notochordal process opens into an arch termed the notochordal plate and attaches overlying neuroepithelium of the neural plate. The notochordal plate then serves as an anchor for the neural plate and pushes the two edges of the plate upwards while keeping the middle section anchored. Some of the notochodral cells become incorporated into the center sectioeural plate to later form the floor plate of the neural tube. The notochord plate separates and forms the solid notochord.
The folding of the neural tube to form an actual tube does not occur all at once. Instead, it begins approximately at the level of the fourth somite at Carnegie stage 9 (around embryonic day
Transverse section of the neural tube showing the floor plate and roof plate
After SHh from the notocord induces its formation, the floor plate of the incipient neural tube also secretes SHH. After closure, the neural tube forms a basal plate or floor plate and an alar plate or roof plate in response to the combined effects of Shh and factors including BMP4 secreted by the roof plate. The basal plate forms most of the ventral portion of the nervous system, including the motor portion of the spinal cord and brain stem; the alar plate forms the dorsal portions, devoted mostly to sensory processing.
The dorsal epidermis expresses BMP4 and BMP7. The roof plate of the neural tube responds to those signals to express more BMP4 and other TGF-b signals to form a dorsal/ventral gradient among the neural tube. The notocord expresses Sonic Hedgehog (Shh). The floor plate responds to Shh by producing its own Shh and forming a gradient. These gradients allows for the differential expression of transcription factors.
In actuality, the folding of the neural tube is still not entirely understood and is still being studied. The simplistic model of the closure occurring in one step cranially and caudally does not explain the high frequency of neural tube defects. Proposed theories include closure of the neural tube occurs in regions, rather than entirely linearly.
In secondary neurulation, the neural ectoderm and some cells from the endoderm form the medullary cord. The medullary cord condenses, separates and then forms cavities. These cavities then merge to form a single tube. Secondary Neurulation occurs in the posterior section of most animals but it is better expressed in birds. Tubes from both primary and secondary neurulation eventually connect.
The anterior segment of the neural tube forms the three main parts of the brain: the forebrain, midbrain, and the hindbrain. Formation of these structures begins with a swelling of the neural tube in a pattern specified by Hox genes. Ion pumps are used to increase the fluid pressure within the tube and create a bulge. A blockage between the brain and the spinal cord prevents the fluid accumulation from leaking out. These brain regions further divide into subregions. The hindbrain divides into different segments called rhombomeres. Neural crest cells form ganglia above each rhombomere. The neural tube becomes the germinal neuroepithelium and serves as a source of new neurons during brain development. The brain develops from the inside-out.
Mesoderm surrounding the notochord at the sides will develop into the somites (future muscles, bones, and contributes to the formation of limbs of the vertebrate).
Masses of tissue called the neural crest that are located at the very edges of the lateral plates of the folding neural tube separate from the neural tube and migrate to become a variety of different but important cells.
Thus, nerve system originates of nerve tube and ganglious lamella. The brain and sense organs are developing from the cranial portion of nerve tube. Middle part of nerve tube and ganglionic plate give rise to spinal cord, dorsal-root ganglia (spinal ganglia), autonomic ganglia and chromaffin tissue of human body. The cells mass especially quiqly increases in the lateral part of nerve tube, whereas dorsal and ventral portions are not inlarged and have ependymal features. At this stage three zones can be recognized in the wall of nerve tube: ependyma, which covers the spinal channel, mantial layer and marginal zone. The innermost layer contains the precursors of glial ependymal cells. Population of middle zone includes two type of cells: neuroblasts and spongyoblasts, whichgive rise accordingly to nerve cells and glial ones (astrocytes and oligodendrocytes). Later grey matter of spinal cord is developing from mantial zone and white matter from outer one.
The development of dorsal-root ganglia and peripheral autonomic ganglia begins at the same time. Ganglionic plate gives the sources for their origin – neuroblasts and glioblasts, which differentiate into neurons and mantial cells of spinal ganglia. Some cells migrate peripherally and there produce autonomic ganglia and chromaffin tissue of adrenal glands medulla.
THE CENTRAL NERVOUS SYSTEM
The central nervous system comprises the brain and spinal cord. It has virtually no connective tissue and is therefore a relatively soft, gel-like organ.
When sectioned, the cerebrum, cerebellum, and spinal cord show regions of white (white matter) and gray (gray matter). The differential distribution of myelin in the central nervous system is responsible for these differences: the main component of white matter is myelinated axons and the myelin-producing oligodendrocytes. White matter almost does not contaierve cells bodies.
Gray matter contains nerve cells bodies, dendrites, and the initial unmyelinated portions of axons and glial cells. This is the region where synapses occur. Gray matter is prevalent at the surface of the cerebrum and cerebellum, forming the cerebral and cerebellar cortex, whereas white matter is present in more central regions.
Myelin sheath of the central nervous system. The same oligodendrocyte forms myelin sheaths for several (3–50) nerve fibers. In the central nervous system, processes of other cells sometimes cover the nodes of Ranvier, or there is considerable extracellular space (ES) at that point. The axolemma shows a thickening where the cell membrane of the oligodendrocyte comes into contact with it. This limits the diffusion of materials into the periaxonal space between the axon and the myelin sheath. At upper left is a surface view of the cell body of an oligodendrocyte. Cyt, cytoplasm of the oligodendrocyte.
BRAIN
There are anterior, middle and posterior brain. Anterior one includes large hemispheres. Brainstem includes another two portions of the brain: midbrain and posterior. The last one consists of pons, cerebellum and medulla oblongata.
Aggregates of nerve cells bodies forming islands of gray matter embedded in the white matter are called nuclei. In the cerebral cortex, the gray matter has six layers of cells with different forms and sizes. Arrangement of nerve cells in layers is termed cytoarchitecture. There are next layers: molecular, external granular, pyramidal, internal granular, ganglion and multiform.
Myeloarchitectureof large hemispheres includes 4 layers of fibers: Exner layer (up to molecular cell layer), Behterev (down) and two layers of Bajarje (up and down to the 5th layer).
Due to the structures, which are interconnecting by fibers, they are dividing into 3 groups: associative, commissural and projective. Fibers of the first group interconnect different parts of cortex of one hemisphere. Commissural ones pass through the comissura thus connecting cells of two hemispheres. Connection of large hemispheres cortex with lower portions of nervous system (subcortical nuclei and spinal cord) is realized by the last group of fibers.
Cerebral cortex is connected with different organs, due to this it is subdivided into fields of Brodman, which allows to explain dissociated disorders of sensory and motor functions in different location of structural changes (damages) of the brain.
Neurons of some regions of the cerebral cortex register afferent (sensory) impulses; in other regions, efferent (motor) neurons generate motor impulses that control voluntary movements. Cells of the cerebral cortex are related to the integration of sensory information and the initiation of voluntary motor responses.
Fields of Brodman, whose cortex is connected with sensory functions, have well prominent granular layers (so called granular cortex). External (2) and internal (4) granular layers are well developed in the audio-vestibular, visual, olfactory centers. They have a lot of cells, which makes them better visible in the slides of brain cortex.
At the same time, those parts of cortex, which are connecting with motor activity, have these layers less prominent, that’s why here the 3, 5 and 6 layers are well developed. Such agranular cortex is typical for the front of brain.
The following slides show some specializations of the brain. First is an overview mid-sagittal cut of the brain, showing the many folds (or gyri) of the external cerebral cortex, and the much smaller, more delicate folds (or folia) of the cerebellar cortex seen to the left. As seen in this kind of cut, the cerebellar folia have a branching, tree-like appearance. (The brain stem is the solid-looking structure along the base of the brain, and continuous with the spinal cord at lower left.)
Section of cerebral cortex, showing cuts of two gyri. The pale cortex follows along the contours of the gyri. White matter (composed of nerve processes) lies below and stains a darker pink. A lot of blood vessels are seen in arachnoid of the brain. Very little cytoarchitecture is seen with H&E stain.
Cerebral cortex stained with silver to show silhouettes of pyramidal cells. Now each triangular cell body can be seen, as well as the ascending apical dendrite, several basal dendrites, and a very fine descending axon. These are specialized multipolar neurons with such a definite shape that they can be recognized as such.
Schematic presentation of brain cortex, which shows typical pyramidal shape of cells.
Associative cortex, motor cortex and sensory cortex.
Silver-stained section of cerebral cortex showing many pyramid-shaped neurons with their processes and a few glial cells.Medium magnification.
Specimen illustrates the typical layered appearance of the cerebral cortex, the more detailed characteristics of each layer being as follows:
1. Plexiform (molecular) layer. This most superficial layer mainly contains dendrites and axons of cortical neurons making synapses with one another; the sparse nuclei are those of neuroglia and occasional horizontal cells of Cajal.
Horizontal cells of Cajal are small and spindle-shaped but oriented parallel to the surface. They are the least common cell type and are only found in the most superficial layer where their axons pass laterally to synapse with the dendrites of pyramidal cells.
2. Outer granular layer. A dense population of small pyramidal cells and stellate cells make up this thin layer which also contains various axons and dendrites connections from deeper layer.
Stellate (granule) cells are small neurons with a short vertical axon and several short branching dendrites giving the cell body the shape of star. With routine histological methods the cells look like small granules giving rise to their alternative name.
3. Pyramidal cell layer. Pyramidal cells of moderate size predominate in this broad layer, the cells increasing in size deeper in the layer.
Pyramidal cells have pyramid-shape cell bodies, the apex being directed towards the cortical surface. A thin axon arises from the base of the cell and passes into the underlying white matter, though in the case of small superficially located cells, the axon may synapse in the deep layers of the cortex. From the apex, a thick branching dendrite passes towards the surface where it has a prolific array of fine dendrites branches. In addition, short dendrites arise from the edges of the base and ramify laterally. The size oh pyramidal cells varies from small to large, the smallest tending to lie more superficially.
4. Inner granular layer. This narrow layer consists mainly of densely packed stellate cells of small size.
5. Ganglionic layer. Large pyramidal cells and smaller numbers of stellate cells and cells of Martinotti make up this layer, the name of the layer originating from the huge pyramidal (ganglion) Betz cells of the motor cortex. Each pyramidal cell is oriented in the layer with apex up to the surface of cortex. The basic part of cell lies deeply. Dendrites arise from the apex of the cell and from the back surfaces. Axon begins from the plate lower surface of the cell and pass down to the white matter.
6. Multiform cell layer. So named on account of the wide variety of differing morphological forms found in this layer, the layer contains numerous small pyramidal cells and cells of Martinotti, as well as stellate cells especially superficially, and fusiform cells in the deeper part.
Cells of Martinotti are small polygonal cells with a few short dendrites and the axon extending toward the surface and bifurcating to run horizontally, most commonly in the most superficial layer.
Fusiform cells are spindle-shaped cells oriented at right angels to the surface. The axon arises from the side of the cell body and passes superficially. Dendrites extend from each end of the cell body branching so as to pass vertically into deeper and more superficial layers.
Huge pyramidal cells are interconnected between themselves in one and two hemispheres. Their axons produce special cortico-cortical fibers. This allows to identify structural unit of large brain cortex – modul– cylinder aroundcortico-cortical fiber (d 300 mkm), which includes all nearest nerve cells connecting with this fiber.
In addition to neurons, the cortex contains supporting neuroglial cells i.e. astrocytes, oligodendrocytes and microglia.
CEREBELLUM
The cerebellum is an important part of the brain and the highest center of balance and coordination of movements of the body, it promoting muscular tension. It is connected with the brain column by afferent and efferent conductive ways, they forming three pairs of cerebellar limbs. In the nuclei of the column switching of the nervous impulses takes place, they coming from the spinal cord, spinal ganglions to the cerebral hemispheres and the cerebellum and in the opposite direction from the column to the cortex. Functional impairment of the cerebellum may occur in intoxication, for example, alcohol intoxication, infections, and traumas. Cerebral column hemorrhages can result in impairments of the subcortical centers, including respiratory, vasomotor centers, with severe consequences for the patient.
The cerebellar cortex has three layers: an outer molecular layer, a central layer of large Purkinje cells, and an inner granular layer. The Purkinje cells have huge cell bodies, a relatively fine axon extending down through the granule cell layer, and their dendrites are highly developed, assuming the aspect of a fan. These dendrites occupy most of the molecular layer and are the reason for the sparseness of nuclei. Special gliocytes (astrocytes) – lophogliocytes lie in this layer. They have a lot of processes, which accompanied dendrites of Purkinje cells, supporting and protect them.
Scheme of Purkinje cell
The outermost molecular layer has two principal types of cells. They are basket and stellate cells. Basket cells are middle-sized multipolar neurons whose bodies lie in the lower part of this layer, close to ganglion layer. Their axons move to the bodies of Purkinje cells and turn around them many times, producing special “basket”. Large stellate cells are very similar; their perikaryons have the same location. Small stellate cells of cerebellar molecular layer are smaller, lie upper and their axons are connecting with dendrites of Purkinje cells in opposite to basket and large stellate cells.
The granular layer is formed by very small neurons (the smallest in the body), which are compactly disposed, in contrast to the less cell-dense molecular layer. There4 are 4 types of cells here. Corn cells are small multipolar neurons whose axons pass up to the molecular layer, making there collaterals parallely to the surface of cortex, and connecting with dendrites of basket, stellate and Purkinje cells. Corn cells are the only cells which transmit the stimuli to the cerebellar cortex. Two types of Golgi cells (with short and long axons) and horizontal cells perform the inhibiting functions.
So, only Purkinje and corn cells are excitatory neurons in cerebellar cortex all the other neurons have inhibiting functions.
Scheme of nerve cells location in cerebellar cortex.
Conductive system of cerebellum
Cerebellum has coordinative function, it regulates balance and muscular tension, that’s why it has a lot of different connections.
Afferent and efferent fibers of cerebellum comprise the nerve fibers, which connect the cerebellar cortex with other structures of nerve system.
Afferent fibers of cerebellum include mosslike and climbing fibers.
Mosslike fibers arise from olives (tr. olivocerebellaris) and cerebellar pons (tr. pontocerebellaris), transmitting stimuli to dendrites of corn cells. Meshwork of these fibers gives name to this structure.
Climbing fibers originate from spinal cord (tr. spinocerebellaris) and vestibular nuclei (tr. vestibulocerebellaris), cross the granular layer and transmit the nerve impulses to the dendrites of Purkinje cells.
The efferent fibers of cerebellum consists mainly of Purkinje cells axons, which move to subcortical nuclei (n.n. dentatus, lentiformis and so on)
Section of cerebellar cortex, showing several folia. Each folium has a central core of bright blue white matter, consisting of nerve processes entering and leaving the superficial cortex. The cortex has an external pale layer and a darker staining granular layer beneath it. Large Purkinje cells lie in a row between these two layers but are not visible at this magnification.
Higher magnification of cerebellar cortex, showing the row of large Purkinje cells lying between the outer and inner cortical layers. The stubs of the dendritic trees of the Purkinje cells look rather like “antlers” arising from the cell bodies. Very complex dendritic brunching actually extend throughout the molecular layer above the Purkinje c ells. A single axon leaves each Purkinje cell at its oval base and descends through the granular layer to deeper relay stations within the brain. Again, these are neurons with a very distinctive shape.
Photomicrograph of the cerebellum. The staining procedure used (H&E) does not reveal the unusually large dendritic arborization of the Purkinje cell. Low magnification.
Section of the cerebellum with distinct Purkinje cells. One Purkinje cell shows part of its rich dendritic arborization. H&E stain. Medium magnification.
Compound reflex arc
Brain is involved iervous activity, being included in compound reflex arc.
A lot of nerve cells which lie in the spinal cord and brain participate in the passage of nerve impulses, they are located between sensory and motor neurons.
Schematic representation of a nerve and a reflex arc. In this example, the sensory stimulus starts in the skin and passes to the spinal cord via the dorsal root ganglion. The sensory stimulus is transmitted to an interneuron that activates a motor neuron that innervates skeletal muscle. Examples of the operation of this reflex are withdrawal of the finger from a hot surface and the knee-jerk reflex.
MENINGES
The central nervous system is protected by the skull and the vertebral column. It is also encased in membranes of connective tissue called the meninges. Starting with the outermost layer, the meninges are the dura mater, arachnoid, and pia mater. The arachnoid and the pia mater are linked together and are often considered a single membrane called the pia-arachnoid.
Dura Mater
The dura mater is the external layer (meninx) and is composed of dense connective tissue continuous with the periosteum of the skull. The dura mater that envelops the spinal cord is separated from the periosteum of the vertebrae by the epidural space, which contains thin-walled veins, loose connective tissue, and adipose tissue.
The dura mater is always separated from the arachnoid by the thin subdural space. The internal surface of all dura mater, as well as its external surface in the spinal cord, is covered by simple squamous epithelium of mesenchymal origin.
Arachnoid
The arachnoid (Gr. arachnoeides, cobweb-like) has two components: a layer in contact with the dura mater, and a system of trabeculae connecting the layer with the pia mater. The cavities between the trabeculae form the subarachnoid space, which is filled with cerebrospinal fluid and is completely separated from the subdural space. This space forms a hydraulic cushion that protects the central nervous system from trauma. The subarachnoid space communicates with the ventricles of the brain.
The arachnoid is composed of connective tissue devoid of blood vessels. Its surfaces are covered by the same type of simple squamous epithelium that covers the dura mater. Since the arachnoid has fewer trabeculae in the spinal cord, it can be more cleanly distinguished from the pia mater in that area.
In some areas, the arachnoid perforates the dura mater, forming protrusions that terminate in venous sinuses in the dura mater. These protrusions, which are covered by endothelial cells of the veins, are called arachnoid villi. Their function is to reabsorb cerebrospinal fluid into the blood of the venous sinuses.
The structure of the meninges, with the superposition of pia mater, arachnoid, and dura mater. Astrocytes form a 3-dimensional net around the neurons (not shown). Note that the footlike processes of the astrocytes form a continuous layer that involves the blood vessels that contribute to the blood-brain barrier.
Pia Mater
The pia mater is a loose connective tissue containing many blood vessels. Although it is located quite close to the nerve tissue, it is not in contact with nerve cells or fibers. Between the pia mater and the neural elements is a thin layer of neuroglial processes, adhering firmly to the pia mater and forming a physical barrier at the periphery of the central nervous system. This barrier separates the central nervous system from the cerebrospinal fluid.
The pia mater follows all the irregularities of the surface of the central nervous system and penetrates it to some extent along with the blood vessels. Pia mater is covered by squamous cells of mesenchymal origin.
Blood vessels penetrate the central nervous system through tunnels covered by pia mater – the perivascular spaces. The pia mater disappears before the blood vessels are transformed into capillaries. In the central nervous system, the blood capillaries are completely covered by expansions of the neuroglial cell processes.
Blood-Brain Barrier
The blood-brain barrier is a functional barrier that prevents the passage of some substances, such as antibiotics and chemical and bacterial toxic matter, from the blood to nerve tissue.
The blood-brain barrier results from the reduced permeability that is a property of blood capillaries of nerve tissue. Occluding junctions, who provide continuity between the endothelial cells of these capillaries, represent the main structural component of the barrier. The cytoplasm of these endothelial cells does not have the fenestrations found in many other locations, and very few pinocytotic vesicles are observed. The expansions of neuroglial cell processes that envelop the capillaries are partly responsible for their low permeability.
HOROID PLEXUS & CEREBROSPINAL FLUID
The choroid plexus consists of invaginated folds of pia mater that penetrate the interior of the ventricles. It is found in the roofs of the third and fourth ventricles and in part in the walls of the lateral ventricles. It is a vascular structure made up of dilated fenestrated capillaries.
Photomicrograph of choroid plexus section. The choroid plexus presents a core of loose connective tissue rich in blood capillaries (BC) covered by a simple cubic epithelium (arrowhead). H&E stain. Medium magnification.
The choroid plexus is composed of loose connective tissue of the pia mater, covered by a simple cuboidal or low columnar epithelium that has the cytologic characteristics of ion-transporting cells.
The main function of the choroid plexus is to elaborate cerebrospinal fluid, which contains only a small amount of solids and completely fills the ventricles, central canal of the spinal cord, subarachnoid space, and perivascular space. Cerebrospinal fluid is important for the metabolism of the central nervous system and acts as a protective device.
Cerebrospinal fluid is very low in protein content. A few desquamated cells and two to five lymphocytes per milliliter are also present. Cerebrospinal fluid circulates through the ventricles, from which it passes into the subarachnoid space. There, arachnoid villi provide the main pathway for absorption of cerebrospinal fluid into the venous circulation. There are no lymphatic vessels ierve tissue.
A decrease in the absorption of cerebrospinal fluid or a blockage of outflow from the ventricles results in the condition known as hydrocephalus (Or. hydro, water, + kephale, head), which promotes a progressive enlargement of the head followed by mental impairment and muscular weakness.
Students’ Practical Activities
Students must know and illustrate such histologic specimens:
Specimen 1.Spinal cord.
Stained with silver impregnation.
The structure of the spinal cord is basically similar over its whole length. In transverse section, the central mass of grey matter has the shape of a butterfly, the ventral horns being most prominent and containing the cell bodies of the large lower motor neurons. The dorsal horns are much less prominent and contain the cell bodies of small second order sensory neurons, which relay sensory information to the brain from primary afferent neurons for the modalities of temperature and pain whose cell bodies lie in the dorsal root ganglia. Small lateral horns, which contain the cell bodies of preganglionic, sympathetic efferent neurons, are found in the thoracic and upper lumbar regions corresponding to the level of the sympathetic outflow from the cord. The volume of grey matter is much more extensive in the cervical and lumbar regions corresponding to the great sensory and motor innervation of the limbs and this is reflected in the much greater diameter of the spinal cord in these areas. The central containing CSF and lined with ependymal cells lies in the central commeasure of grey matter.
The white matter of the spinal cord consist of ascending tracts of sensory fibers and descending motor tracts; passing up the spinal cord towards the brain, more and more fibers enter and leave the cord so that the volume of white matter increases progressively from the sacral to cervical regions.
Externally, the spiral cord has a deep ventral median fissure but dorsally there is only a shallow dorsal midline sulcus. On each side, a dorso-lateral sulcus marks the line of entry of the dorsal nerve roots.
Illustrate and indicate: 1.Anterior median sulcus; 2.Posterior median septum; 3.Central canal; 4.Ventral (anterior) horn; 5.Dorsal (posterior) horn; 6.Lateral (intermediate) horn; 7.Ventral white column; 8.Lateral white column; 9.Dorsal white column; 10.Multipolar neurons.
Specimen 2. Spinal node (dorsalroot ganglion).
Stained with hematoxylin and eosin.
At a low magnification of microscope find anterior and posterior spinal cord roots and on the last one – spinal node, which is cowered by the connective tissue capsule. Distinct (exact) disposition of pericarions and nerve cells processes is the characteristic sign of spinal ganglion. Large pseudounipolar neurons with light vesiclelike nuclei are disposed peripherally right under the capsule. nerve processes occupy the middle part of the node. At a high microscope magnification find the sheath of small glial (mantial) cells with large dark nuclei around the nerve cells. Thin connective tissue layer surrounds the neurons outside. In fibroblasts and fibrocytes you may observe elongated nuclei with heterochromatine.
Illustrate and indicate: 1. Capsule 2. Dorsal root 3.Ventral root 4.Ganglion cells 5. Satellite cells 6.Bundle of the nerve fibers 7. Fibroblasts (nuclei) in the interstitial tissue.
Specimen 3. Nerve (transverse section in human skin).
Stained with haematoxylin and eosin.
At a low magnification of the microscope nerve trunk is seen to consist of separate nerve fibers bandles. Outside it is cowered by the connective tissue capsule – epineurium. Each bandle of nerve fibers is surrounded by perineurium. Thin connective tissue layer, which arise from perineurium inside inbetween the nerve fibers, forms the endoneurium.
Illustrate and indicate: 1. Nerve (nerve trunk). 2. Fasciculi of mielinated nerve fibers. 3. Nerve fiber. 4.Endoneurium. 5. Perineurium. 6. Epineurium.
Cross section of a thick nerve showing the epineurium, perineurium, and endoneurium. The myelin sheath that envelops each axon was partially removed by the histologic technique. PT stain. Medium magnification.
Low power view of longitudinal section of peripheral nerve, again showing distinct division into bundles of processes. The “‘waviness” of the processes themselves is often typical of nerve.
Cross-cut of a peripheral nerve showing characteristically round bundles of nerve processes surrounded by pale gray-blue connective tissue sheaths. The outer connective tissue sheath surrounding the entire nerve is the epineurium. The connective tissue sheath surrounding each round bundle is the perineurium. Surrounding each individual nerve process within a bundle is the delicate connective tissue endoneurium (not visible at this magnification).
Reflex arc
In terms of a simple reflex arc (sensory information comes to the cord and motor information is sent from the cord) picture some basic nerve cell bodies and processes as follows:
A pseudounipolar, sensory cell body lies within the spinal ganglion. It has one long dendrite coming in from the extreme right in this picture, from the body periphery (either from muscle or skin). This dendrite is continuous with the cell body (no synapses are involved here). The cell’s axon leaves along the same “stalk” with the dendrite and then turns to course through the dorsal root, into the spinal cord. There its axonal endings synapse upon the dendrites of a small, intermediate multipolar neuron lying in the dorsal horn of the gray matter. This intermediary cell sends its axon to the ventral horn of the, gray matter and synapses upon the dendrites of a large, multipolar, motor neuron lying there. The axon of the motor neuron courses out of the cord via the ventral root and proceeds out of this picture, to the right, until it ends Upon voluntary muscle.
Schematic representation of a nerve and a reflex arc. In this example, the sensory stimulus starts in the skin and passes to the spinal cord via the dorsal root ganglion. The sensory stimulus is transmitted to an interneuron that activates a motor neuron that innervates skeletal muscle. Examples of the operation of this reflex are withdrawal of the finger from a hot surface and the knee-jerk reflex.
Specimen 4. Cerebral cortex.
Silver impregnation.
The cerebral hemispheres consist of a convoluted cortex of grey matter overlying the central medullary mass of white matter which conveys fibers between different parts of the cortex and to and from other parts of the central nervous system. The neurons are arranged into six layers, the layers differing in characteristic neurone morphology, size and population density. The layers merge with one another rather than being highly demarcated and vary somewhat from one region of the cortex to another depending on cortical thickness and function.
Specimen illustrates the typical layered appearance of the cerebral cortex, the more detailed characteristics of each layer being as follows:
1. Plexiform (molecular) layer. This most superficial layer mainly contains dendrites and axons of cortical neurons making synapses with one another; the sparse nuclei are those of neuroglia and occasional horizontal cells of Cajal.
Horizontal cells of Cajal are small and spindle-shaped but oriented parallel to the surface. They are the least common cell type and are only found in the most superficial layer where their axons pass laterally to synapse with the dendrites of pyramidal cells.
2. Outer granular layer. A dense population of small pyramidal cells and stellate cells make up this thin layer which also contains various axons and dendrites connections from deeper layer.
Stellate (granule) cells are small neurons with a short vertical axon and several short branching dendrites giving the cell body the shape of star. With routine histological methods the cells look like small granules giving rise to their alternative name.
3. Pyramidal cell layer. Pyramidal cells of moderate size predominate in this broad layer, the cells increasing in size deeper in the layer.
Pyramidal cells have pyramid-shape cell bodies, the apex being directed towards the cortical surface. A thin axon arises from the base of the cell and passes into the underlying white matter, though in the case of small superficially located cells, the axon may synapse in the deep layers of the cortex. From the apex, a thick branching dendrite passes towards the surface where it has a prolific array of fine dendrites branches. In addition, short dendrites arise from the edges of the base and ramify laterally. The size oh pyramidal cells varies from small to large, the smallest tending to lie more superficially.
4. Inner granular layer. This narrow layer consists mainly of densely packed stellate cells.
5. Ganglionic layer. Large pyramidal cells and smaller numbers of stellate cells and cells of Martinotti make up this layer, the name of the layer originating from the huge pyramidal (ganglion) Betz cells of the motor cortex.
6. Multiform cell layer. So named on account of the wide variety of differing morphological forms found in this layer, the layer contains numerous small pyramidal cells and cells of Martinotti, as well as stellate cells especially superficially, and fusiform cells in the deeper part.
Cells of Martinotti are small polygonal cells with a few short dendrites and the axon extending toward the surface and bifurcating to run horizontally, most commonly in the most superficial layer.
Fusiform cells are spindle-shaped cells oriented at right angels to the surface. The axon arises from the side of the cell body and passes superficially. Dendrites extend from each end of the cell body branching so as to pass vertically into deeper and more superficial layers.
In addition to neurons, the cortex contains supporting neuroglial cells i.e. astrocytes, oligodendrocytes and microglia.
Illustrate and indicate: I. Cerebral cortex: 1. Plexiform (molecular) layer; 2. Outer granular layer; 3.Pyramidal cell layer; 4.Inner granular layer; 5.Ganglionic layer; 6.Multiform cell layer; II.White matter.
Specimen 5.Cerebellum.
Stained with H&E.
Higher magnification of cerebellar cortex, showing the row of large Purkinje cells lying between the outer and inner cortical layers. The stubs of the dendritic trees of the Purkinje cells look rather like “antlers” arising from the cell bodies. Very complex dendritic brunching actually extend throughout the molecular layer above the Purkinje c ells. A single axon leaves each Purkinje cell at its oval base and descends through the granular layer to deeper relay stations within the brain. Again, these are neurons with a very distinctive shape.
As seen in specimen, the cerebellum cortex forms a series of deeply convoluted folds or folia supported by a branching central medulla of white matter. The cortex is seen to consist of three layers, an outer layer containing relatively few cells (the so-called molecular-layer), an extremely cellular inner layer (the so-called granule cell layer) and a single intervening layer of huge neurons called Purkinje cells. The Purkinje cells have huge cell bodies, a relatively fine axon extending down through the granule cell layer, and an extensively branching dendritic system, which arborises into the outer molecular layer.
The deep granule cell layer of the cortex contains numerous small neurons, the non-myelinated axons of which pass outwards to the molecular layer where they bifurcate to run parallel to the surface to synapse with the dendrities of Purkinje cells; each granule cell synapses with several hundred Purkinje cells. There are three other types of small neurons in the cerebellar cortex, namely, stellate cells and basket cells scattered in the outer molecular layer and Golgi cells scattered in the superficial part of the granule cell layer.
Illistrate and indicate:
References:
a) basic
1. Practical classes materials.
3. Stevens A. Human Histology / A.Stevens, J.Lowe. – [second edition]. –Mosby, 2000. – P. 86-98.
4. Wheter’s Functional Histology :A Text and Colour Atlas / [Young B., Lowe J., Stevens A., Heath J.]. – Elsevier Limited, 2006. – P. 392-399.
5. Ross M. Histology : A Text and Atlas / M. Ross W.Pawlina. – [sixth edition]. – LippincottWilliamsandWilkins, 2011. – P. 390-398.
b) additional
6. Eroschenko V.P. Atlas of Histology with functional correlations / Eroschenko V.P. [tenthedition]. – Lippincott Williams and Wilkins, 2008. – P. 135-171.
7. Charts:
http://intranet.tdmu.edu.ua/index.php?dir_name=kafedra&file_name=tl_34.php#n15
8. Volkov K. S. Ultrastructure of cells and tissues / K. S. Volkov, N. V. Pasechko. – Ternopil :Ukrmedknyha, 1997. – P. 6-20.
http://en.wikipedia.org/wiki/Histology
http://www.meddean.luc.edu/LUMEN/MedEd/Histo/frames/histo_frames.html
http://www.udel.edu/biology/Wags/histopage/histopage.htm