2.3.4. Test questions
Choose the appropriate letter(s)!
1. The motor nuclei of which cranial nerves belong to the dorsomedial group? (A, B, D) A. oculomotor n.
B. trochlear n.
C. trigeminal n.
D. abducens n.
E. facial n.
2. Which of these cranial nerves contain general visceromotor fibers? (A, C, D) A. oculomotor n.
B. trochlear n.
C. facial n.
D. glossopharyngeal n.
E. hypoglossal n.
3. What types of fibers does the vagus nerve contain? (A, B, D) A. general visceromotor
E. special somatosensory
4. Which of the following ganglia are the autonomic ganglia of the facial nerve? (C, D) A. geniculate ganglion
B. otic ganglion
C. pterygopalatine ganglion D. submandibular ganglion E. ciliary ganglion
5. Which of the following ganglia are sensory ganglia? (A, B, E) A. trigeminal ganglion
B. geniculate ganglion C. otic ganglion D. ciliary ganglion
E. superior ganglion of glossopharyngeal nerve
6. Which nerve provides the motor innervation of the muscles of mastication? (B) A. phrenic n.
B. trigeminal n.
C. facial n.
D. glossopharyngeal n.
E. hypoglossal n.
7. What part of the brain does the hypoglossal nerve originate from? (E) A. Telencephalon
B. Diencephalon C. Mesencephalon D. Pons
E. Medulla oblongata
8. Where does the maxillary nerve leave the skull? (C) A. inferior orbital fissure
B. pterygomaxillary fissure C. foramen rotundum
A. oculomotor n.
B. trochlear n.
C. trigeminal n.
D. vagus n.
E. accessory n.
10. Which cranial nerves pass through the jugular foramen? (D, E) A. trochlear n.
B. abducens n.
C. facial n.
D. glossopharyngeal n.
E. vagus n.
11. Where are the spinal ganglia located? (D) A. On the dorsal ramus of the spinal nerve.
B. On the ventral root, directly before formation of the spinal nerve.
C. On the ventral root, directly next to the spinal cord.
D. On the dorsal root, directly before formation of the spinal nerve.
E. On the dorsal root, directly next to the spinal cord.
12. What types of fibers does the ventral root contain? (C, D) A. somatosensory
B. viscerosensory C. somatomotor D. visceromotor E. none of these
13. What types of fibers may be present in a spinal nerve? (A, B, C, D) A. somatosensory
B. viscerosensory C. somatomotor D. visceromotor E. none of these
C. ...the ventral rami of the spinal nerves.
D. ...the dorsal rami of the spinal nerves.
E. ...the anterior and posterior rootlets.
15. Where are the cell bodies of the visceromotor neurons of the spinal cord located? (C) A. ventral horn
B. dorsal horn C. lateral horn
D. inferior salivary nucleus E. Edinger-Westphal nucleus Links:
Spinal and epidural anesthesia: http://www.youtube.com/watch?v=dHp7lGzwWxE Spinal cord segment: http://www.youtube.com/watch?v=LwuV5JbgCNk
References
Trepel: Neuroanatomie. Struktur und Funktion. Urban and Fischer, 3. Auflage
Mathias Bähr, Michael Frotscher: Duus’ Neurologisch-topische Diagnostik. Thieme, 8. Auflage
Dr. Hajdu Ferenc: Vezérfonal a neuroanatómiához. 2. átdolgozott és bővített kiadás. SOTE, Budapest, 1996 Ryan S, Blyth P, Duggan N, Wild M, Al-Ali S.: Is the cranial accessory nerve really a portion of the accessory
nerve? Anatomy of the cranial nerves in the jugular foramen. Anat. Sci. Int. 82(1):1-7, 2007
3. 1.c. The light- and electronmicroscopic structure of the peripheral nerves (axons, sheets, terminals). – Judit Horváth [Translator-reviser: Dóra Reglődi]
3.1. 1. Summary
The most important element of the peripheral nerve is the nerve fiber, which consists of the axon and the sheath surrounding it. The axon is the longest process of the nerve cell; its length may exceed 1 m. The axon cannot survive if separated from the soma. The entire nerve cell builds an anatomical-morphological, trophic, functional and pathological unit; hence, we may not speak about the peripheral nerve without describing the nerve cell. Understanding the structure of the nerve cell and the connection between the perikaryon and the axon is essential for understanding its normal function and regeneration.
A nerve cell consists of the cell body (perikaryon or soma), dendrites, axon, and axon-terminal (telodendron).
Approximately 95% of all nerve cells are multipolar (many dendrites, one axon); 4% are pseudounipolar (the single process of the perikaryon divides into a central and peripheral process); and 1% are bipolar (1 dendrite – one axon, or central and peripheral process). The perikaryon of the nerve cell is located in the central nervous system or in a peripheral ganglion; peripheral nerves do not contain nerve cells.
organelles (receptors) that are specialized for receiving stimuli, or terminate as free nerve endings.
The pseudounipolar nerve cells are located in the sensory ganglia, always close to the central nervous system (in the sensory ganglia of the cranial nerves, and along the spinal cord the spinal ganglia). As an exception, the nerve cells in the ganglia of the vestibulocochlear nerve retained their ancient bipolar form. The central processes of these pseudounipolar or bipolar cells grow into the central nervous system and synapse with multipolar cells (e.g. in the dorsal horn of the spinal cord, sensory nuclei of the cranial nerves); through this synapsing, the possibility of further processing of the stimuli arriving from the periphery is established.
The preganglionic cells of the autonomic nervous system are always in the central nervous system. These are multipolar cells, their axons synapse with multipolar ganglionic cells in the periphery. In case of the sympathetic nervous system, these ganglionic cells are close to the vertebral column, while the parasympathetic fibers end in ganglia close to the target organs, and are embedded into the wall of the organ. The axons of the ganglion cells are the postganglionic fibers that innervate the target organs (en passant synapses, autonomic plexuses).
The sensory and motor roots of the spinal cord connect to each other in the spinal nerve. The branches of the spinal nerve (ventral and dorsal rami) contain both sensory and motor fibers. As the fibers enter or exit the spinal cord their sheath changes; in the central nervous system the myelin sheath is given by oligodendrocytes, while in the periphery (cca. 1 mm from the spinal cord) by Schwann cells. As long as the nerve fibers are protected by the skull or vertebral column, the connective tissue sheaths between and around the nerve fibers are much thinner than on the ”true” periphery after exiting the skull or the intervertebral foramina.
In peripheral nerves the sheath of the nerve fibers may be myelin sheath from multiple layers of duplicated membranes of Schwann cells (myelinated fibers), or simply by the cytoplasm of Schwann cells (non-myelinated fibers). The sheath around the axon disappears just before its termination. The conduction speed of the nerve fiber (axon + sheath!) depends on the thickness of the axon and the myelin sheath. The thickest nerve fibers are the ones innervating muscles. Their diameter is 15-20 micrometers, and the conduction velocity may reach 100-120 m/s (=360-430 km/h!). The diameter of non-myelinated fibers (e.g. autonomic postganglionic fibers and slow/dull pain fibers) is 0.1-1 micrometer, and their conduction velocity is slower than 1 m/s.
Bundles of nerve fibers in the periphery are called peripheral nerves. They may be affected mechanically under normal circumstances, so their structure has to comply with these requirements. Examining a larger nerve (e.g.
median nerve, diameter cca. 5 mm) we find multiple pre-packed bundles, these bundles may divide to even smaller bundles. The nerve fiber bundles within a nerve are embedded into a connective tissue with fat cells, which contains blood vessels; this is called epineurium. The bundles seen with low magnification are surrounded by perineurium, which has an inner cellular layer composed of flattened cells and an outer collagenous fibrous layer. The cell connections (zonulae occludentes) and the basal membranes between the inner cellular layers provide mechanical and chemical protection to the nerve. The nerve fibers are within the perineurium, separated from each other by minimal connective tissue; this is the endoneurium, which contains small vessels. Examining a slide from a peripheral nerve (if the slide is thick enough and we move the micrometer screw), often a whirlpool-like picture may be observed which reflects the spiraling course of the nerve fibers. The system of connective tissue covering organized in three layers and the spiral course of the nerve fibers (compare to the traditional telephone wire) ensures that the peripheral nerves withstand all harmful effects. great Hungarian anatomist, Mihály Lenhossék. The theory was further developed by Waldeyer; he was the first to use the term “neuron”. The main parts of the neuron are the cell body (perikaryon or soma), the dendrites (may be numerous), the axon (a nerve cell has a single axon), and at the end of the axon the telodendron, through which it may connect to another nerve cell, or to a peripheral effector cell.
According to the neuron doctrine, the nerve cell is
• a functional unit: if stimuli of sufficient strength through synapses depolarize the neuron, the depolarization wave extends in the entire cell (“all or nothing”), it has no grades
• trophic unit: the processes are kept alive by the perikaryon which constantly reproduces plasma organelles.
The processes do not survive if detached from the perikaryon. Under optimal circumstances the axon may regenerate. In this case its elements are synthesized in the perikaryon, and are carried by axonal transport to the injured territory, from where the process rebuilds (see later *** 6.)
Similarly to the epithelial cells, the nerve cells are polarized cells. The theory of histodynamic polarity was first described by Cajal. This means that under physiological circumstances the depolarization proceeds from the cell body in the direction of the telodendron (this is true in most cases, even according to the latest scientific results).
The telodendron connects to the dendrite or cell body of another neuron through synapses. The chemical synapses allow only unidirectional transmission of the depolarization.
3.3. 3. Nervous tissue in general
The nervous tissue consists of nerve cells (neurons) and glial cells. With the help of their processes the neurons connect to other nerve cells, and in the periphery (skin, muscle, tendon, etc.) or viscera to receptors or effectors.
The membrane of neurons may be stimulated by another neuron or, in the peripheral or visceral receptors, by mechanical, thermal, or chemical insult. The electrical current travels along the axon, in case of the afferent fibers from the periphery to the CNS (central nervous system), while in case of the efferent fibers in the opposite direction.
The other major cell types of the nervous tissue are the glial cells. There are different types of glial cells, their distribution is characteristic in the given region of the nervous system, and their presence is essential for the proper function of the nervous system. Their functions include ensheathing axons and feeding and isolating nerve cells. The processes of macroglial cells seal the inner and outer surface of the CNS.
3.3.1. 3.1. The nerve cell
3.3.1.1. 3.1.1. The main parts of the neuron
• Cell body (perikaryon or soma). Its size may vary from 5 to 150 micrometers. Nerve cells having a longer axon usually have larger perikarya; so for example, the motoneurons of the anterior horn are typically large neurons.
• Dendrites (multipolar nerve cells have many dendrites): extend from the cell body like branches of a tree, branch in acute angles, and get thinner. Depolarization of axon terminals of other nerve cells reaches usually the dendrites, through synapses. Depending on the size of the dendritic, tree the number of synapses may be a few hundred, but it may reach also 200,000 (e.g. in the case of Purkinje cells in the cerebellum).
• Axon: the stimulus travels along the axon from the perikaryon. The axon is in most cases covered by a sheath, the ensheathed axon is called nerve fiber. (The terms axon and nerve fiber are not always used consistently in the literature!) Along its course, the thickness of the axon is uniform; its side branches are called collaterals.
• Both the collaterals and the “main” axon end in telodendron: the axon, close to its terminal divides to small branches; the club-shaped thickenings of these pass on the stimuli through synapses to other neurons or effectors (glandular cells, muscle).
In the synapses, the electric stimulus is transmitted to the postsynaptic structure through chemical substances (transmitters). The only possible reaction of the next cell, in case the stimulus was of sufficient strength, is depolarization.
In case of convergence, the axons of several nerve cells reach a single neuron. The axons of the ventral horn motoneurons are the motor fibers in the peripheral nerves. On these motoneurons, there are about 10,000
external stimuli.
3.3.1.2. 3.1.2. Classification of neurons
Neurons may be classified according to several characteristics. Based on their connections, those neurons, which through their axons connect to distant regions, are called projection neurons (Golgi type I). Neurons with short axons are called Golgi type II neurons; these synapse with nerve cells in their vicinity. Most neurons belong to the second group.
Neurons may be stimulatory or inhibitory neurons. These may be further classified according to their characteristic transmitter: e.g. the stimulatory neurons use acetylcholine, glutamate, aspartate, dopamine, noradrenaline, serotonin, neuropeptides, adenosine, and nitrogen-monoxide. For the inhibitory nerve cells gamma-amino butyric acid (GABA) and glycine are most common. (Medications acting on the nervous system often target the transmitters.)
However, most commonly we classify the nerve cells according to their shape.
3.3.1.2.1. 3.1.2.1. Morphological characterization of neurons
• Apolar neurons, without processes are briefly present during the differentiation of nerve cells, in the early phase of development.
• Unipolar nerve cell have a single process, they are common in primitive animals. In the human nervous system, they are rarely found. The amacrine cells of the retina are special unipolar cells with one richly branching dendrite.
• Bipolar cells have a dendrite (peripheral process) and an axon (central process). They are typically found in the retina and in the inner ear (spiral and vestibular ganglia). They give less than 1% of all nerve cells.
• Pseudounipolar neurons are 4-5% of all nerve cells. These are typical in the spinal ganglia (Fig. 1), and in most sensory ganglia of cranial nerves. During development, these cells are first bipolar, then the two processes approach each other and unite. As a result, special round neurons with one process arising from the perikaryon are formed that have no synapses on their perikarya. Because of the special shape and function of these cells, the processes are not called dendrite and axon, but peripheral and central process. From the cell body, one single process extends that coils around the soma several times and then bifurcates in T-shape to its two processes. The peripheral process brings the information from the receptor; the depolarization directly proceeds to the central process, which transmits it to the multipolar neurons of the CNS. Both processes are ensheathed, according to their fine structure they are axons. The special feature of this cell is that the stimulus proceeds from the end of an axon-like process in the direction of the perikaryon.
Figure 1.13. Figure 1.: A. Pseudounipolar nerve cells in a sensory ganglion, HE staining. The satellite cells are arranged in a ring around the large neurons. B.
Pseudounipolar nerve cells in a sensory ganglion, silver-nitrate impregnation. The
neurons have a single process.
• In humans, cca. 95% of nerve cells are multipolar neurons, with many dendrites and one axon (Fig. 2). Their shapes and sizes may vary; many of them have proper names (e.g. pyramidal cell (Fig. 3), stellate cell, basket cell, Purkinje cell (Fig. 4), granular cell, etc.). The depolarization reaches the dendrites or the soma through the synapses, and if the cell gets depolarized, the action potential travels down along the axon.
Figure 1.14. Figure 2.: Multipolar nerve cells in an autonomic ganglion, silver-nitrate impregnation. Multiple dendrites branch from a neuron. Each cell has one axon, but this is rarely seen in the plane of the cut
Figure 1.15. Figure 3.: Pyramidal cells in the cerebral cortex, Golgi impregnation
neurons, recycling the transmitters, stabilizing the ion concentration of the extracellular space, cleaning up tissue debris, and making myelin sheath. Scientific research of the last decade supports the view that the importance of glial cells is much greater than just being the “connective tissue” of the nervous system. Glial cells are of ectodermal origin, with the exception of the microglia.
3.3.2.1. 3.2.1. Glial cells of the central nervous system
• Astrocytes (macroglia). Cells with multiple processes, they have two major types: fibrous astrocytes (Fig. 5), mostly in the white matter, and protoplasmic astrocytes in the grey matter. Their main functions are:
formation of the blood-brain barrier, supply of nutrients and oxygen to neurons, electric insulation of neurons, supportive function, phagocytosis, and forms “scar tissue” after injuries of the nervous system. They are positive for GFAP.
(GFAP - glial fibrillary acidic protein - is an intermediate filament protein, expressed by astrocytes, Bergmann glia cells, and ependymal cells of the central nervous system, and also by other cells in different other tissues.)
Figure 1.17. Figure 5.: Fibrous astrocytes, AuCl impregnation. The processes of the glial cells terminate around blood vessels
• Oligodendroglial cells have a small cell body, with their flattened processes form myelin sheath around 5-50 axons running in their vicinity, with this isolating them electrically from the surrounding tissues.
Oligodendroglial cells are GFAP negative.
• Ependymal cells line the ventricular system. Covering the choroid plexus, they play a role in liquor production. Their kinocilia promote liquor circulation. Ependymal cells may function as nervous stem cells.
They are GFAP positive.
• Radial glial cells, in their original form, play a role in the development of the nervous system. Their characteristic form is best retained in the Bergman glia cells of the cerebellum and in the Müller cells of the retina. Radial glial cells are GFAP positive.
Figure 1.18. Figure 6.: A. Resting microglia cells. B. Activated microglia cells. (C3 receptor immunohistochemistry) (Courtesy of Dr. Hajnalka Ábrahám, PTE ÁOK Electron Microscopy Laboratory)
3.3.2.2. 3.2.2. Glial cells in the peripheral nervous system
• Schwann cells ensheath the axons in the periphery (myelin sheath or in case of non-myelinated fibers Schwann sheath). They have phagocytic capacity.
• Satellite cells are small cells surrounding the neurons of ganglia. Their function is similar to that of astrocytes.
• Enteral glial cells are found in the wall of intestines around neurons of the enteral nervous system. In cooperation with the neurons, they act on gastrointestinal motility.
3.4. 4. Light and electron microscopic structure of neurons
3.4.1. 4.1. Perikaryon
The perikaryon (cell body or soma) is the part of the cell where all necessary elements are synthesized. The nucleus is euchromatic with few heterochromatin granules. The nucleolus is well visible.
The cytoplasm contains free ribosomes, rosettes of ribosomes, and rough endoplasmic reticulum. In some neurons, the rough endoplasmic reticulum consists of several parallel lamellae; this is called Nissl substance. In light microscopy, these appear as Nissl granules (or tigroid granules, the term was suggested by Mihály Lenhossék). The light microscopic appearance of Nissl granules may be fine or coarse (Fig 7). With electron microscope, Golgi apparatus, mitochondria, and lysosomes are also detectable. Some cells contain brown pigment granules: this may be lipofuscin, an aging or "wear-and-tear" pigment composed of lipid-containing residues of lysosomal digestion. It is a type of lipochrome. A specific population of neurons synthesizing dopamine or noradrenaline (nucleus coeruleus, substantia nigra) may contain neuromelanin.
Figure 1.20. Figure 8.: Lipofuscin (electron micrograph ). (Courtesy of Dr. Hajnalka
Ábrahám, PTE ÁOK Electron Microscopy Laboratory)
The cytoskeleton is made up of microtubules (neurotubules, consist of tubulin, diameter cca. 20 nm), intermediate filaments (diameter cca. 10 nm), and actin filaments (diameter cca. 5 nm). The cytoskeletal elements give mechanical stability to the soma and processes and provide transport to cell organelles and substances within the cell and its processes. The cytoskeletal elements are anchored to each other by microtubule-associated proteins (MAP).
Synapses are present on the surface of the soma, but most of the synapses are located on the dendrites.
3.4.2. 4.2. Dendrites
Dendrites are the projections of the neuron, branching at acute angle. They get thinner as they get more distant from the cell body. The structure of their initial segment does not differ from the soma (with this it differs from the axon), but in their thinner parts the number of cell organelles diminishes. On their surface, often bulb-like protrusions are seen; these are the dendritic spines (Fig. 9). Most synapses are found on the surfaces of dendrites