The human body consists of numerous tissues and organs, which are diverse in structure and function, yet they function together and in harmony for the well-being of the body as a whole. It is obvious that there has to be some kind of influence that monitors and controls the working of different parts of the body. Although there are other mechanisms that help in such control (for example hormones), the overwhelming role in directing the activities of the body rests with the nervous system. Neuroanatomy is the study of the structural aspects of the nervous system. It cannot be emphasized too strongly that the study of structure is meaningless unless correlated with function.
Figure 1.1: Anatomical divisions of the nervous system. The central nervous system consists of the brain and spinal cord. The peripheral nervous system consists of cranial nerves and spinal nerves.
DIVISIONS OF NERVOUS SYSTEM
The nervous system may be divided into the central nervous system (CNS), made up of the brain and spinal cord, the peripheral nervous system(PNS), consisting of the peripheral nerves and the ganglia associated with them, and the autonomic nervous system(ANS), consisting of the sympathetic and the parasympathetic nervous systems (Figures 1.1 and 1.2) (Table 1.1). The brain consists of the cerebrum, diencephalon, midbrain, pons, cerebellum and medulla oblongata. The midbrain, pons, and medulla oblongata together form the brainstem. The medulla oblongata is continuous below with the spinal cord (Figure 1.2).
The peripheral nerves include those that supply skin, muscles, and joints of the body wall and limbs, and those that supply visceral structures, for example, heart, lungs, stomach, etc. Each of these sets of peripheral nerves is intimately associated with the brain and spinal cord. Peripheral nerves attached to the brain are called cranial nerves, and those attached to the spinal cord are called spinal nerves (Figure 1.2). The nerves supplying the body wall and limbs are often called craniospinal nerves. The nerves supplying the viscera, along with the parts of the brain and spinal cord related to them, constitute the ANS. The ANS is subdivided into two major parts—the sympathetic and the parasympathetic nervous systems.
TISSUES CONSTITUTING NERVOUS SYSTEM
The nervous system is made up, predominantly, of tissue that has the special property of being able to conduct impulses rapidly from one part of the body to another.
The specialized cells that constitute the functional units of the nervous system are called neurons.
Within the brain and spinal cord, neurons are supported by a special kind of connective tissue that is called neuroglia.
Nervous tissue, composed of neurons and neuroglia, is richly supplied with blood. It was earlier thought that lymph vessels were not present in the brain. However, recently it has been shown that interstitial fluid from brain 3parenchyma drains through lymphatics, that travel along the wall of the arterioles and arteries of the brain.
The nervous system of man is made up of innumerable neurons. The total number of neurons in the human brain is estimated to be more than 1 trillion. The neurons are linked together in a highly intricate manner. It is through these connections that the body is made aware of changes in the environment or of those within itself and appropriate responses to such changes are produced, for example, in the form of movement or in the modified working of some organ of the body. The mechanisms for some of these relatively simple functions have come to be known as a result of a vast amount of work done by numerous workers for over a century. There is no doubt that higher functions of the brain, like those of memory and intelligence, are also to be explained on the basis of connections between neurons, but as yet, little is known about the mechanisms involved. Neurons are, therefore, to be regarded not merely as simple conductors, but as cells that are specialized for the reception, integration, interpretation, and transmission of information.
Note:
Nerve cells can convert information obtained from the environment into codes that can be transmitted along their axons. By such coding, the same neuron can transmit different kinds of information.
STRUCTURE OF A TYPICAL NEURON
Neurons vary considerably in size, shape, and other features. However, most of them have some major features in common and these are described below.
A neuron consists of a cell body that gives off a number of processes called neurites (Figure 1.3A and B).
The cell body is also called the soma or perikaryon. Like a typical cell, it consists of a mass of cytoplasm surrounded by a cell membrane. The cytoplasm contains a large central nucleus (usually with a prominent nucleolus), numerous mitochondria, lysosomes, and a Golgi complex (Figure 1.3B). In the past, it has often been stated that centrioles are not present in neurons, but studies with the electron microscope (EM) have shown that centrioles are present.
In addition to these features, the cytoplasm of a neuron has some distinctive characteristics that are not seen in other cells.
The cytoplasm shows the presence of a granular material that stains intensely with basic dyes. This material is the Nissl substance (also called Nissl bodies or granules) (Figure 1.3C). When examined with the EM, these bodies are seen to be composed of rough surfaced endoplasmic reticulum (Figure 1.3B). The presence of abundant granular endoplasmic reticulum is an indication of the high level of protein synthesis in the neurons. The proteins are needed for production of neurotransmitters and enzymes as well as maintenance and repair.
Another distinctive feature of neurons is the presence of a network of fibrils permeating the cytoplasm. These neurofibrils are seen, with the EM, to consist of microfilaments and microtubules (Figure 1.3D). The centrioles present in neurons may be concerned with the production and maintenance of microtubules.
Some neurons contain pigment granules (for example, neuromelanin in neurons of the substantia nigra). Aging neurons contain a pigment, lipofuscin (made up of residual bodies derived from lysosomes).
Neurites
The processes arising from the cell body of a neuron are called neurites. These are of two kinds. Most neurons give off a number of short branching processes called dendrites and one longer process called an axon.
The dendrites are characterized by the fact that they terminate near the cell body. They are irregular in thickness and Nissl granules extend into them (Figure 1.3C). They bear numerous small spines that are of variable shape. Some additional features of dendrites are:
- Dendrites can be distinguished immunocytochemically from axons because of the presence of microtubule associated protein (MAP-2), not present in axons.
- Dendritic spines vary in size and shape. Some spines contain aggregations of smooth endoplasmic reticulum (in the form of flattened cisternae with associated dense material). The complex is referred to as the spine apparatus.
- Actin filaments are present in dendritic spines.
The axon may extend for a considerable distance away from the cell body. The longest axons may be as much as a meter long. Each axon has a uniform diameter and is devoid of Nissl substance (Figure 1.3C).
In addition to these differences in structure, there is a fundamental functional difference between dendrites and axons. In a dendrite, the nerve impulse travels towards the cell body whereas in an axon the impulse travels away from the cell body. A summary of the differences between dendrite and axon is shown in Table 1.2.
Axon Hillock and Initial Segment
The axon is free of Nissl granules. The Nissl-free zone extends for a short distance into the cell body. This part of the cell body is called the axon hillock. The part of the axon just beyond the axon hillock is called the initial segment (Figure 1.3B and C).
The axon hillock and the initial segment of the axon are of special functional significance. This is the region where action potentials are generated (spike generation), resulting in conduction along the axon. The initial segment is unmyelinated. It often receives axoaxonal synapses that are inhibitory. The plasma membrane, here, is rich in voltage-sensitive channels.4
Figure 1.3B: Schematic representation of some structural features of neuron as seen by electron microscope
Figure 1.3C: Neuronal cell body shows Nissl substance.
Note: The Nissl substance is not present in the axon and in the region of axon hillock but extends into proximal dendrites
Figure 1.3D: Neuronal cell body shows neurofibrils
Note: The neurofibrils extend into both axons and dendrites
|
Termination of Axon
An axon may give off a variable number of branches. Some branches, which arise near the cell body and lie at right angles to the axon are called collaterals. At its termination, the axon breaks up into a number of fine branches called telodendria that may end in small swellings (terminal boutons or bouton terminaux) (Figure 1.3A). An axon (or its branches) can terminate in two ways. Within the CNS, it always terminates by coming in intimate relationship with another neuron, the junction between the two neurons being called a synapse. Outside the CNS, the axon may end in relation to an effector organ (for example, muscle or gland), or may end by synapsing with neurons in a peripheral ganglion.
Axoplasmic Flow
The cytoplasm of neurons is in constant motion. Movement of various materials occurs through axons. This axoplasmic flow takes place both away from and towards the cell body. The flow away from the cell body is greater. Some materials travel slowly (0.1–2 mm a day) constituting a slow transport. In contrast, other materials (mainly in the form of vesicles) travel 100–400 mm a day constituting a rapid transport.
Slow transport is unidirectional, away from the cell body. It is responsible for flow of axoplasm (containing various proteins) down the axon. Rapid transport is bidirectional and carries vesicular material and mitochondria. Microtubules play an important role in this form of transport. Retrograde axoplasmic flow may carry neurotropic viruses (see below) along the axon into the neuronal cell body.
Axoplasmic transport of tracer substances introduced experimentally can help to trace neuronal connections.
Clinical Correlation
Role of axoplasmic transport in spread of disease
Some infections, which affect the nervous system travel along nerves.
- Rabies is a disease (often fatal), caused by a bite of a rabid dog (and some other animals, including monkeys). The saliva of an infected animal contains the rabies virus. The virus travels from the site of the bite to the CNS, along nerves by reverse axoplasmic flow and causes infection there. As this means of transport is slow, there is a delay of a few days between the bite and appearance of symptoms. The duration of this delay depends on the length of the nerve fibres concerned. A bite on the face produces symptoms much faster than on the foot.
- The virus of poliomyelitis is also transported (from the gastrointestinal tract) to the nervous system through reverse axoplasmic flow.
- In contrast, tetanus travels from the site of infection to the brain along the endoneurium of nerve fibres.
Neuropil
Many regions of the brain and spinal cord are occupied by a complex meshwork of axon terminals, dendrites and processes of neuroglial cells. This meshwork is called the neuropil.
CLASSIFICATION OF NEURONS
Anatomical Classification
Variation in the Shape of Neuronal Cell Bodies
Neurons vary considerably in the size and shape of their cell bodies (somata) and in the length and manner of branching of their processes (Figures 1.4 and 1.5). The cell body varies in diameter from about 5 µm, in the smallest neurons, to as much as 120 µm in the largest ones. The shape of the cell body is dependent on the number of processes arising from it.
The most common type of neuron gives off several processes, and the cell body is, therefore, multipolar. Some neurons have only one axon and one dendrite and are bipolar (Figures 1.4 and 1.5).
Another type of neuron has a single process (which is highly convoluted). After a very short course, this process divides into two.6
One of the divisions represents the axon; the other is functionally a dendrite, but its structure is indistinguishable from that of an axon. This neuron is described as unipolar, but from a functional point of view, it is to be regarded as bipolar. To avoid confusion on this account, this kind of neuron has been referred to as a pseudounipolar neuron in the past, but this term has now been discarded. Depending on the shapes of their cell bodies, some neurons are referred to as stellate (star-shaped) or pyramidal.
In addition to the variations in size and shape, the cell bodies of neurons may show striking variations in the appearance of the Nissl substance. In some neurons, the Nissl substance is very prominent and is in the form of large clumps. In some others, the granules are fine and uniformly distributed in the cytoplasm, while yet other neurons show gradations between these extremes. These differences are correlated with function.
Variations in Axons
The length of the axon arising from the cell body of a neuron is also subject to considerable variability.
Figure 1.5: Types of neurons—anatomical classification
Note: In unipolar neurons, after a very short course the process divides into two. One of the divisions represents the axon, and the other is functionally a dendrite, but its structure is indistinguishable from that of an axon. This neuron is described as unipolar, but from a functional point of view, it is to be regarded as bipolar. To avoid confusion on this account, this kind of neuron has been referred to as a pseudounipolar neuron.
- Golgi type I neurons have long axons and connect remote regions.
- Golgi type II neurons or microneurons/interneurons have short axons that end near the cell body. These are often inhibitory in function (Table 1.3).
- Very rarely, a neuron may not have a true axon, for example, amacrine neurons of the retina.
As stated earlier, axons also differ in the nature of the sheaths covering them, some of them being myelinated and others unmyelinated. Axons also show considerable variation in the diameter of their cross-sections.
Variations in Dendrites
Dendrites arising from a neuronal cell body vary considerably in number and in the extent and manner of branching. They also differ in the distribution of spines on them. These characteristics are of functional importance. The area occupied by the dendrites of a neuron is referred to as its dendritic field.
The field may be spherical (as in stellate cells), hemispherical, disk-like, conical, or flat. In some neurons (for example, pyramidal), there may be two separate dendritic fields. Apart from shape, there is considerable variability in the extent of the dendritic field. Some neurons (for example, Golgi neurons of the cerebellum) have dendritic fields covering a very wide area. More than 80% of the neuronal surface area (excluding the axon) may be situated on the dendritic tree.
|
7The frequency of branching of dendrites is correlated with the number of synapses on them. In some neurons, the dendritic spines may number several thousand. Finally, it may be emphasized that the dendritic tree is not a ‘fixed’ entity, but may undergo continuous remodeling. This affords a basis for modification of neuronal behaviour.
NERVE FIBRES
Axons (and some dendrites, which resemble axons in structure) constitute what are commonly called nerve fibres.
The bundles of nerve fibres found in CNS are called as tracts, while the bundles of nerve fibres found in PNS are called peripheral nerves.
Basic Structure of Peripheral Nerve Fibres
Each nerve fibre has a central core formed by the axon. This core is called the axis cylinder. The plasma membrane surrounding the axis cylinder is the axolemma.
The axis cylinder is surrounded by a myelin sheath. This sheath is in the form of short segments that are separated at short intervals called the nodes of Ranvier. The part of the nerve fibre between two consecutive nodes is the internode.
Each segment of the myelin sheath is formed by one Schwann cell.
Outside the myelin sheath, there is a thin layer of Schwann cell cytoplasm and an external lamina (similar to the basal lamina of epithelium). This layer of cytoplasm and external lamina is called the neurilemma. Neurilemma is important in the regeneration of peripheral nerves after their injury.
Note:
Such neurilemma is absent in oligodendrocytes that form myelin sheath in CNS. Hence, regeneration in the CNS is not possible.
Each nerve fibre is surrounded by endoneurium (Figure 1.6). This is a layer of connective tissue. The endoneurium holds adjoining nerve fibres together and facilitates their aggregation to form bundles or fasciculi.
Each fasciculus is surrounded by the perineurium (Figure 1.6) that is a thicker layer of connective tissue. The perineurium is made up of layers of flattened cells separated by layers of collagen fibres. The perineurium probably controls diffusion of substances in and out of axons.
A very thin nerve may consist of a single fasciculus, but usually a nerve is made up of several fasciculi. The fasciculi are held together by the epineurium. This is a fairly dense layer of connective tissue that surrounds the entire nerve.
Clinical Correlation
- The epineurium contains fat that cushions nerve fibres. Loss of this fat in bedridden patients can lead to pressure on nerve fibres and paralysis.
- Blood vessels to a nerve travel through the connective tissue that surrounds it. Severe reduction in blood supply can lead to ischemic neuritis and pain.
Blood-nerve Barrier
Peripheral nerve fibres are separated from circulating blood by a blood-nerve barrier. Capillaries in nerves are non-fenestrated and their endothelial cells are united by tight junctions. There is a continuous basal lamina around the capillary. The blood-nerve barrier is reinforced by cell layers present in the perineurium.
Classification of Peripheral Nerve Fibres
According to Function
- Some nerve fibres carry impulses from the spinal cord or brain to peripheral structures like muscle or gland; they are called efferent or motor fibres. Efferent fibres are axons of neurons, the cell bodies of which are located in the grey matter of the spinal cord or of the brainstem
- Other nerve fibres carry impulses from peripheral organs to the brain or spinal cord. These are called afferent fibres. Many (but not all) afferent fibres are concerned in the transmission of sensations like touch, pain, etc. They are, therefore, also called sensory fibres. Afferent nerve fibres are processes of neurons that are located (as a rule) in sensory ganglia.
In the case of spinal nerves, these ganglia are located on the dorsal nerve roots. In the case of cranial nerves, they 8are located on ganglia situated on the nerve concerned (usually near its attachment to the brain). The neurons in these ganglia are usually of the unipolar type. Each unipolar neuron gives off a peripheral process, which passes into the peripheral nerve forming an afferent nerve fibre. It also gives off a central process that enters the brain or spinal cord.
From what has been said above, it will be clear that the afferent nerve fibres in peripheral nerves are functionally dendrites. However, their histological structure is exactly the same as that of axons.
According to Area of Innervation
According to the area of innervation, the nerve fibres within the spiral nerves may be classified into the following types:
- Somatic sensory fibres: They convey impulses from skin, bones, muscles, and joints to the CNS.
- Somatic motor fibres: They carry impulses from CNS to the skeletal muscles.
- Visceral sensory fibres: They convey impulses from visceral organs and blood vessels to the CNS.
- Visceral motor fibres: (also called autonomic motor fibres) They carry impulses from CNS to the cardiac muscle, glands, and smooth muscles within the viscera.
According to Diameter and Velocity of Conduction
In a transverse section across a peripheral nerve, it is seen that the nerve fibres vary considerably in diameter. Fibres of larger diameter are myelinated while those of smallest diameters are unmyelinated. Large fibres of larger diameter conduct impulses more rapidly than those of smaller diameter. Various schemes for classification of nerve fibres on the basis of their diameter and their conduction velocity have been proposed. The best known classification is as follows (Table 1.4).
Type A
The fastest conducting fibres are called type A fibres. Their conduction velocity is 12–120 m/s, and their diameter varies from 2 µm to 20 µm. They are myelinated.
Type A fibres are further divided (in descending order of diameter and conduction velocity) into four subtypes: alpha (A α), beta (A β) gamma (A γ), and delta (A δ). Type A fibres perform both motor and sensory functions as follows:
Motor type A fibres
- Aα fibres supply extrafusal fibres in skeletal muscle.
- Aγ fibres supply intrafusal fibres in muscle spindles.
- Aδ fibres are collaterals of Aα fibres (to extrafusal fibres) that innervate some intrafusal fibres.
Sensory type A fibres
- A α sensory fibres carry impulses from encapsulated receptors in skin, joints, and muscle. They include primary sensory afferents from muscle spindles (also called Group Ia fibres), Golgi tendon organs (also called Group Ib fibres), and secondary afferents from spindles, touch, and pressure (also called Group II fibres). Some of them carry impulses from the gut.
- Aδ sensory fibres (also called Group III fibres) are afferents from thermoreceptors and nociceptors (pain receptors).
Type B
Type B fibres have a conduction velocity of 3–15 m/s and their diameter is 1–5 µm. They are myelinated. They are either preganglionic autonomic efferent fibres (motor) or afferent fibres from skin and viscera, and from free nerve endings in connective tissue of muscle (also called Group III fibres).
Type C
In contrast to type A and type B fibres, type C fibres are unmyelinated. They have a conduction velocity of 0.5–2 m/s, and their diameter is 0.2–1.5 µm. These are postganglionic autonomic fibres and some sensory fibres conveying pain. These include nociceptive fibres from connective tissue of muscle (also called Group IV fibres). Some fibres from thermoreceptors and from viscera also fall in this category.
|
Unmyelinated axons are numerous in dorsal nerve roots and in cutaneous nerves. All postganglionic autonomic nerve fibres are unmyelinated, although preganglionic nerves are myelinated fibres.
MYELINATED AND NONMYELINATED NERVE FIBRES
A myelinated nerve fibre is one that is surrounded by a myelin sheath. The myelin sheath is formed by oligoden-drocyte in the CNS and by Schwann cell in the PNS.
Small diameter axons, for example, those of the ANS and small pain fibres, are simply enveloped by the cytoplasm of Schwann cells. These nerve fibres are said to be non-myelinated.
Myelin Sheath
The nature of myelin sheath is best understood by considering the mode of its formation (Figure 1.7).
An axon lying near a Schwann cell invaginates into the cytoplasm of the Schwann cell. In this process, the axon comes to be suspended by a fold of the cell membrane of the Schwann cell. This fold is called the mesaxon (Figure 1.8).
In some situations, the mesaxon becomes greatly elongated and comes to be spirally wound around the axon, which is thus surrounded by several layers of cell membrane. Lipids are deposited between adjacent layers of the membrane. These layers of the mesaxon, along with the lipids, sphingomyelin, form the myelin sheath.
Outside the myelin sheath, a thin layer of Schwann cell cytoplasm and an external lamina persists to form an additional sheath, which is called the neurilemma (also called the neurilemmal sheath or Schwann cell sheath).
An axon is related to a large number of Schwann cells over its length. Each Schwann cell provides the myelin sheath for a short segment of the axon (Figure 1.9). At the junction of any two such segments, there is a short gap in the myelin sheath. These gaps are called the nodes of Ranvier. The part of the nerve fibre between two such nodes is called the internode. The length of the internode is greater in thicker fibres and shorter in thinner ones. It varies from 150 to 1500 µm.
The nerve fibres within a nerve frequently branch. When they do so, the bifurcation always lies at a node.
Nodes of Ranvier
The nodes of Ranvier have great physiological importance. When an impulse travels down a nerve fibre, it does not proceed uniformly along the length of the axis cylinder, but jumps from one node to the next. This is called saltatory conduction.
In unmyelinated neurons, the impulse travels along the axolemma. Such conduction is much slower than saltatory conduction and consumes more energy.
Myelination does not occur simultaneously in all axons. A myelinated tract becomes fully functional only after its fibres have acquired myelin sheaths.
Nerve fibres are not fully myelinated at birth. Myelination is rapid during the first year of life and becomes much slower thereafter. This is to be correlated with the gradual ability of an infant to perform more complicated actions.
Further Consideration of the Structure of the Myelin Sheath
From Figure 1.10, it will be seen that each layer of plasma membrane helping to form the myelin sheath has an internal or cytoplasmic surface that comes in contact with the internal surface of the next layer, and an external surface that meets the external surface of the next layer. When the myelin sheath is examined with the higher magnifications of the electron microscope (EM), it shows alternate thick and thin lines. The thick lines (called period lines or major dense lines) represent the fused cytoplasmic surfaces of two adjacent layers of the plasma membrane, whereas the thin lines (called intraperiod lines or minor dense lines) represent the fused external surfaces of two adjacent membranes.
Figure 1.8: Stages in the formation of the myelin sheath by a Schwann cell—The axon, which first lies near the Schwann cell (A), invaginates into its cytoplasm (B and C), and comes to be suspended by a mesaxon. The mesaxon elongates and comes to be spirally wound around the axon (D and E). Lipids are deposited between the layers of the mesaxon.
Figure 1.9: Scheme to show that each Schwann cell forms a short segment of the myelin sheath. The small figures at the extreme right are transverse sections through the nerve fibre, at the corresponding stages
Some other terms of interest are shown in Figure 1.10.
Incisures of Schmidt Lanterman
With the light microscope, oblique clefts are often seen in the myelin sheath (Figure 1.11). These clefts are called the Schmidt Lanterman clefts. EM studies show the clefts to be areas where adjoining layers of Schwann cell plasma membrane (forming the myelin sheath) have failed to fuse leaving a layer of Schwann cell cytoplasm that passes spirally around the axon in the position of the period line and a spiral space through which the perineural space communicates with the periaxonal space in the position of the intraperiod line. This space provides a path for passage of substances into the myelin sheath and axon, from the space around the nerve fibre. The clefts enlarge greatly when a nerve fibre undergoes Wallerian degeneration.
Composition of Myelin Sheath
Myelin contains protein, lipids, and water. The main lipids present include cholesterol, phospholipids, and glycos-phingolipids. Other lipids are present in smaller amounts.
Clinical Correlation
Myelination can be seriously impaired, and there can be abnormal collections of lipids, in disorders of lipid metabolism. Various proteins have been identified in myelin sheaths and abnormality in them can be the basis of some neuropathies.
The composition and structure of myelin sheaths formed by oligodendrocytes show differences from those formed by Schwann cells. The two are different in protein content and can be distinguished by immunocytochemical methods. As damage to neurons within the CNS is not followed by regeneration, oligodendrocytes have no role to play in this respect. In multiple sclerosis, myelin formed by oligodendrocytes undergoes degeneration, but that derived from Schwann cells is spared
Functions of the Myelin Sheath
- The presence of a myelin sheath increases the velocity of conduction (for a nerve fibre of the same diameter).
- It reduces the energy expended in the process of conduction.
Figure 1.10: Scheme to explain the significance of period and intraperiod lines seen in the myelin sheath as viewed under electron microscope
Nonmyelinated Fibres
There are some axons, which are devoid of myelin sheaths and examples include postganglionic autonomic fibres. The nonmyelinated fibres are also surrounded by Schwann cells. These unmyelinated axons invaginate into the cytoplasm of Schwann cells, but the mesaxon does not spiral around them (Figure 1.12). Another difference is that several such axons may invaginate into the cytoplasm of a single Schwann cell.
In unmyelinated neurons, the impulse travels along the axolemma. Such conduction is much slower than saltatory conduction and consumes more energy.
MYELINOGENESIS
Myelinogenesis is the process of sequential myelination around nerve fibres of the nervous system. The myelination process allows action potentials to propagate faster. Thus there is better connectivity within brain regions allowing the brain to specialize further. Myelination begins in the third trimester of intrauterine life and continues up to almost the fourth decade of postnatal life!
The myelination of peripheral motor roots is completed within the first month of postnatal life, the sensory roots takes a longer time and complete their myelination in six months. The pyramidal tracts (for voluntary motor activity) and the striatal pathways (for automatic associated movements) complete their myelination by two to three years. However, the fine co-ordination of movements which require the cortico-ponto-cerebellar circuit, complete their myelination only by the fourth year. Teaching a nursery child or play-school child to write, and expect the writing to be neat, is fundamentally against myelinogenesis!
Sensory thalamic radiations myelinate at different times. The optic radiation complete myelination by six months; the somaesthetic radiation by one year; the 12auditory radiation is completed only by three years. Although reticulospinal pathway for automatic breathing starts functioning (and hence myelinated) at birth, the entire myelination of the reticular system is completed only in the second decade (during adolescence).
Cerebral cortical myelination continues to third to fourth decade of life. The motor cortex myelinates first followed by somatosensory cortex. Association cortices myelinate late. The limbic lobe of cingulate gyrus, the inferior temporal lobe for long term memory and the prefrontal cortex governing personality are the last areas to complete their myelination.
GREY AND WHITE MATTER
Sections through the spinal cord or through any part of the brain show certain regions that appear whitish, and others that have a darker greyish colour. These constitute the white and grey matter, respectively.
Microscopic examination shows that the cell bodies of neurons are located only in grey matter that also contains dendrites and axons starting from or ending on the cell bodies. Most of the fibres within the grey matter are unmyelinated.
On the other hand, the white matter consists predominantly of myelinated fibres. It is the reflection of light by myelin that gives this region its whitish appearance.
Neuroglia and blood vessels are present in both grey and white matter.
The arrangement of the grey and white matter differs at different regions in the brain and spinal cord. In the spinal cord and brainstem, the white matter is on the outside, whereas the grey matter forms one or more masses embedded within the white matter. In the cerebrum and cerebellum, there is an extensive, but thin, layer of grey matter on the surface. This layer is called the cortex. Deep to the cortex, there is white matter, but within the latter, several isolated masses of grey matter are present.
Isolated spherical masses of grey matter present anywhere in the CNS are referred to as nuclei (red nucleus, oculomotor nucleus). As grey matter is made of cell bodies of neurons (and the processes arising from or terminating on them), nuclei can be defined as groups of cell bodies of neurons present within the CNS.
Aggregations of the cell bodies of neurons found outside the CNS are referred to as ganglia.
Some neurons are located in nerve plexuses present in close relationship to some viscera. These are referred to as ganglionated plexuses.
The axons arising in one mass of grey matter terminate very frequently by synapsing with neurons in other masses of grey matter. The axons connecting two (or more) masses of grey matter are frequently numerous enough to form recognizable bundles. Such aggregations of fibres are called tracts.
Larger collections of fibres are also referred to as funiculi, fasciculi, or lemnisci. A lemniscus is a ribbon like band. Large bundles of fibres connecting the cerebral or cerebellar hemispheres to the brainstem are called peduncles.
Aggregations of processes of neurons outside the CNS constitute peripheral nerves.
BASIC NEURONAL ARRANGEMENTS
The nerve fibres that make up a peripheral nerve can be divided into two major types as follows:
- Fibres that carry impulses from the CNS to an effector organ (e.g. muscle or gland) are called efferent or motor fibres.
- Fibres that carry impulses from peripheral structures (e.g. skin) to the CNS are called afferent fibres. Some afferent fibres carry impulses that make us conscious of sensations like touch or pain. Such fibres may, therefore, be called sensory fibres. Other afferent fibres convey information, which is not consciously perceived, but is necessary for reflex control of various activities of the body.
Both afferent and efferent fibres can be further classified on the basis of the tissues supplied by them. The tissues and organs of the body can be broadly divided into two major categories—somatic and visceral.
Somatic structures are those present in relation to the body wall (or soma). They include the tissues of the limbs (which represent a modified part of the body wall). Thus, the skin, bones, joints, and striated muscles of the limbs, and body wall are classified as somatic.
Visceral structures, in contrast, are those that make up the internal organs like the heart, lungs, or stomach. These include the lining epithelia of hollow viscera and smooth muscle.
A distinction between somatic and visceral structures may also be made on embryological considerations.
- Structures developing from specialized areas of ectoderm, e.g. the retina and membranous labyrinth, are classified as somatic while the epithelium of the tongue (and taste buds), which is of endodermal origin is classified as visceral.
- Striated muscle may be derived, embryologically, from three distinct sources. These are:
- The somites developing in the paraxial mesoderm
- The somatopleuric mesoderm of the body wall
- The mesoderm of the branchial arches
The musculature of the limbs and body wall develops partly from somites and partly in situ from the mesoderm of the body wall. The nerves supplying this musculature are classified as somatic. The muscles that move the eyeball, and the muscles of the tongue are also derived from somites and the nerves supplying them are, therefore, also classified as somatic. However, striated muscle that develops in the mesoderm of the branchial arches is classified as visceral.13
Hence, the muscles of the face, the muscles of mastication, and the muscles of the pharynx and larynx are regarded as visceral.
Keeping in view the distinction between afferent and efferent fibres on one hand and somatic and visceral structures on the other, fibres in peripheral nerves can be divided into four broad categories.
These are:
- Somatic efferent
- Visceral efferent
- Somatic afferent
- Visceral afferent
With the exception of somatic efferent fibres, each of the categories named above is subdivided into a general and a special group. Thus, there are a total of seven functional components as follows:
- Somatic efferent (or somatomotor, GSE) fibres supply striated muscles of the limbs and body wall. They also supply the extrinsic muscles of the eyeballs and the muscles of the tongue.
- General visceral efferent fibres (also called visceromotor fibres, GVE) supply smooth muscle and glands. The nerves to glands are called secretomotor nerves.
- Special visceral efferent (SVE) fibres supply striated muscle developing in branchial arch mesoderm. They are frequently called branchial efferent or branchiomotor fibres. The muscles supplied include those of mastication and of the face, pharynx, and larynx.
- General somatic afferent(GSA) fibres are those that carry:
- Sensations of touch, pain, and temperature from the skin (exteroceptive impulses)
- Proprioceptive impulses arising in muscles, joints, and tendons conveying information regarding movement and position of joints
- Special somatic afferent (SSA) fibres carry impulses of:
- Vision
- Hearing
- Equilibrium
- General visceral afferent (GVA) fibres (also called visceral sensory fibres) carry sensations, e.g. pain from viscera (visceroceptive sensations).
- Special visceral afferent (SVA) fibres carry the sensation of taste.
A typical spinal nerve contains fibres of the four general categories. The special categories are present in cranial nerves only.
Somatic Efferent Neurons
These neurons carry nerve impulses from CNS to striated muscles (Figure 1.13).
In the spinal cord, the cell bodies of these neurons lie in the ventral grey column. They are often referred to as anterior horn cells. The neurons are large and multipolar and their Nissl substance is prominent. They are designated as α-motor neurons to distinguish them from smaller anterior horn cells called γ-motor neurons.
The axon of a somatic efferent neuron leaves the spinal cord through a ventral nerve root to enter the spinal nerve concerned. During its course through the spinal nerve (and its branches), the axon divides into a variable number of branches, each one of which ultimately ends by supplying one muscle fibre. The region of junction between a terminal branch of the axon and the muscle fibre has a special structure and is called the motor end plate or neuromuscular junction (Figure 1.14).14
Motor Unit
Depending on the number of branchings, one anterior horn cell supplies a variable number of muscle fibres. One anterior horn cell and the muscle fibres supplied by it constitute one motor unit (Figure 1.14). In large muscles, where strength of contraction is more important than precision, a motor unit may contain up to 2000 muscle fibres. On the other hand, in muscles where precision is all important (e.g. in muscles of the eyeball), the motor unit may supply as few as six fibres.
The somatic efferent fibres of cranial nerves are axons of neurons, the cell bodies of which lie in somatic efferent nuclei in the brainstem. Their axons pass through the third, fourth, and sixth cranial nerves to supply the extrinsic muscles of the eyeballs and through the twelfth cranial nerve to supply muscles of the tongue.
Figure 1.14: Schematic diagram to show a motor unit consisting of a number of muscle fibres innervated by a single motor neuron
Special Visceral Efferent Neurons(Branchiomotor Neurons)
These are seen only in relation to cranial nerves. The cell bodies of these neurons are located in the branchial efferent nuclei of the brainstem. Their axons pass through the fifth, seventh, ninth, tenth, and eleventh cranial nerves to supply striated muscle derived from the branchial arches. The relationship of these neurons to striated muscle is the same as that of somatic efferent neurons.
General Visceral Efferent Neurons
These are the neurons that constitute the autonomic nervous system (sympathetic and parasympathetic). They supply smooth muscle or glands. The nerves to glands are called secretomotor nerves. The pathway for the supply of smooth muscle or gland always consists of two neurons that synapse in a ganglion (Figure 1.15). The first neuron carries the impulse from the CNS to the ganglion and is, therefore, called the preganglionic neuron. The second neuron carries the impulse from the ganglion to smooth muscle or gland and is called the postganglionic neuron.
The cell bodies of preganglionic neurons of the sympathetic nervous system are located in the lateral grey column of the spinal cord, in the thoracic and upper two lumbar segments (Figure 1.15). Their cell bodies are multipolar but are smaller than those of somatic efferent neurons. The Nissl substance in them is also less prominent. The axons leave the spinal cord through the anterior nerve roots of spinal nerves and terminate in a sympathetic ganglion.
15The cell bodies of postganglionic neurons are located in sympathetic ganglia and in some cases, in peripherally situated ganglia and, plexuses. The axons of these postganglionic neurons terminate in relation to smooth muscle in the walls of blood vessels and in viscera. They also supply the arrectores pilorum muscles of the skin and give a secretomotor supply to sweat glands.
The cell bodies of preganglionic neurons of the parasympathetic nervous system are located in two different situations.
- One group is located in the lateral grey column of the spinal cord in the second, third, and fourth sacral segments. Their axons end in peripheral ganglia (or plexuses) situated in intimate relationship to pelvic viscera. These ganglia contain the cell bodies of postganglionic neurons. The axons of these neurons are short and end by supplying smooth muscle or glands of the viscera concerned.
- The other group of parasympathetic preganglionic neurons is located in the general visceral efferent nuclei of cranial nerves. The axons of these neurons terminate in autonomic ganglia associated with the third, seventh, ninth, and tenth cranial nerves. The postganglionic neurons are situated in these ganglia. They supply smooth muscle or glands.
Afferent Neurons
Afferent nerve fibres can be divided into four categories, viz. general somatic afferent, special somatic afferent, general visceral afferent, and special visceral afferent. The basic arrangement of the neurons that give origin to all four categories of afferent fibres is similar and the description that follows applies to all of them.
The cell bodies of neurons that give rise to efferent fibres of peripheral nerves are located within the brain and spinal cord. In contrast, the cell bodies of neurons that give rise to afferent fibres are located outside the CNS. In the case of spinal nerves, the cell bodies lie in the spinal ganglia and in the case of the cranial nerves, they lie in sensory ganglia, (e.g. the trigeminal ganglion) associated with these nerves. The arrangement of an afferent neuron with reference to a spinal nerve is illustrated in Figure 1.16.
The cells of the dorsal nerve root ganglion are of the unipolar variety. Each cell gives off a single process that divides into a peripheral process and a central process. The peripheral process extends into the spinal nerve and courses through its branches to reach the tissue or organ supplied. It may branch repeatedly during its course. These peripheral processes are functionally dendrites, as they convey impulses towards the cell body, but they are indistinguishable in structure from axons. These processes constitute the sensory fibres of peripheral nerves. The sensory impulses brought by these processes from various organs of the body are conveyed to the spinal cord by the central processes (representing axons). Within the spinal cord, the central processes usually run a short course and terminate by synapsing with cells in the posterior grey column. Some of the central processes are, however, long. They enter the posterior funiculus and run upwards to the medulla as ascending tracts.
The sensory ganglia of the fifth, seventh, ninth, and tenth cranial nerves are made up of cells similar to those of the spinal ganglia. Their central processes end by synapsing with cells in the sensory nuclei of these nerves. The sensory ganglia of the eighth nerve (i.e. the cochlear and vestibular ganglia) are peculiar, in that their neurons are bipolar, the two processes corresponding to the central and peripheral processes of unipolar neurons. They subserve special somatic afferent function.
Arrangement of Neurons withinthe Central Nervous System
The arrangement of neurons considered so far are of two types:
- Having cell bodies that lie within the brain and spinal cord and sending out efferent processes that leave the CNS to form the motor fibres of peripheral nerves.
- Having cell bodies located in ganglia outside the CNS but sending processes into it.
The bulk of the CNS is, however, made up of neurons that lie entirely within it. As explained earlier, the cell bodies of these neurons are invariably located in masses of grey matter. The axons may be short, ending in close relation to the cell body (short axon neurons or Golgi type II neurons), or may be long (long axon neurons or Golgi type I neurons) and may travel to other masses of grey matter lying at considerable distances from the grey matter of origin. The neurons within the CNS are interconnected in an extremely intricate manner. The basic arrangement encountered can be understood by understanding of reflexes and their mechanism.
Reflex Action and Types of Reflexes
A reflex action is defined as an immediate, involuntary motor response of the muscles in response to a specific sensory stimulus. For example, if the skin of the sole of a sleeping person is scratched, the leg is reflexly drawn up.
The simplest possible arrangement and the mechanism of reflex are shown in Figure 1.17. The stimulus applied to the skin gives rise to a nerve impulse, which is carried by the peripheral process of a unipolar neuron to the spinal ganglion. From here, the impulse passes into the central process, which terminates by directly synapsing with an anterior horn cell supplying the muscle which draws the leg up. The complete pathway constitutes a reflex arc, and in the above example, it consists of two neurons—one afferent and the other efferent. As only one synapse is involved, the reflex is monosynaptic.
In actual practice, however, the reflex arc is generally made up of three neurons as shown in Figure 1.18. The central process of the dorsal nerve root ganglion cell ends by synapsing with a neuron lying in the posterior grey column. This neuron has a short axon that ends by synapsing with an anterior horn cell, thus completing the reflex arc. The third neuron interposed between the afferent and efferent neurons is called an internuncial neuron or simply an interneuron. For obvious reasons, such a reflex is said to be polysynaptic. It is important to know that various tendon reflexes are dependent on monosynaptic reflex arcs.
The purpose served by an interneuron may be basically of three types. Firstly, the axon arising from an interneuron may be divided into a number of branches and may synapse with a number of efferent neurons (Figure 1.19A). As a result, an impulse coming along a single afferent neuron may result in an effector response by a large number of efferent neurons. Secondly, afferent impulses brought by a number of afferent neurons may converge on a single efferent neuron through the agency of interneurons (Figure 1.19B). Some of these impulses tend to induce activity in the efferent neuron (i.e., they are facilitatory), while others tend to suppress activity (i.e., they are inhibitory). Thirdly, through interneurons, an afferent neuron may establish contact with efferent neurons in the opposite half of the spinal cord or in a higher or lower segment of the cord.
Some reflexes are protective, e.g. withdrawal of the hand when a hot object is touched. In such a movement involving withdrawal, joints of the extremity are flexed. Such reflexes are, therefore, also called flexor reflexes. When a person is standing, a series of reflexes are active to prevent him from falling. As these keep the body straight (with the hip and knee joints extended), they are called extensor reflexes or antigravity reflexes.
Figures 1.19A and B: Schemes to illustrate two roles which internuncial neurons may play—the internuncial neurons are shown in blue lines
Maintenance of posture through such reflexes is influenced by the membranous labyrinth, the cerebellum, and other centres in the brain. Vision is also important in maintaining correct posture.
Every time a stimulus reaches a neuron, it does not mean that it must become active and must produce an impulse. A neuron receives inputs from many neurons (in some cases, from hundreds of them). Some of these inputs are facilitatory and others are inhibitory. Activity in the neuron (in the form of initiation of an impulse) depends on the sum total of these inputs. Thus, each neuron may be regarded as a decision-making centre. The greater the number of neurons involved in any pathway, the greater the possibility of such interactions. Viewed in this light, it will become clear that interneurons interposed in a pathway increase the number of levels at which ‘decisions’ can be taken. It will also be appreciated that most of the neurons within the nervous system are, in this sense, interneurons, which are involved in numerous highly complex interactions on which the working of the nervous system depends.
From what has been said above, it will be seen that some activities occur due to reflex action and may involve only neurons within the spinal cord. However, most activities of the spinal cord are subjected to influence from higher centres. In the more complicated types of activity, several higher centres may be involved and the pathways may be 18extremely complicated. Afferent impulses reaching these higher centres (e.g. the cerebral cortex) would appear to be somehow stored and this stored information (of which one may or may not be conscious) is used to guide responses to similar stimuli received in future. This accounts for memory and for learning processes.
DEGENERATION AND REGENERATION OF NEURONS
When the axon of a neuron is crushed or cut across, a series of degenerative changes are seen in the axon distal to the injury, in the axon proximal to the injury, and in the cell body.
Anterograde Degeneration
The changes in the part of the axon distal to the injury are referred to as anterograde degeneration or Wallerian degeneration. They take place in the entire length of this part of the axon (Figure 1.20).
- A few hours after injury the axon becomes swollen and irregular in shape, and in a few days, it breaks up into small fragments.
- The neurofibrils within it break down into granules.
- The myelin sheath breaks up into small segments. It also undergoes chemical changes that enable degenerating myelin to be stained selectively.
- The region is invaded by numerous macrophages that remove degenerating axons, myelin, and cellular debris. These macrophages probably secrete substances that cause proliferation of Schwann cells and also produce nerve growth factors.
- The Schwann cells increase in size and produce a large series of membranes that help form numerous tubes. These tubes play a vital role in regeneration of nerve fibres.
Retrograde Degeneration
Degenerative changes in the neuron proximal to the injury are referred to as retrograde degeneration. These changes take place in the cell body and in the axon proximal to injury.
Degenerative Changes Inside the Cell Body
The cell body of the injured neuron undergoes a series of changes that constitute the phenomenon of chromatolysis.
The cell body enlarges tending to become spherical. The nucleus moves from the centre to the periphery. The Nissl substance becomes much less prominent and appears to dissolve away; hence, the term chromatolysis.
Ultrastructural and histochemical alterations occur in the cell body. The severity of the reaction shown by the cell body is variable. In some cases, chromatolysis ends in cell death, followed by degeneration of all its processes. The reaction is more severe when the injury to the axon is near the cell body. If the cell survives, the changes described above are reversed after a period of time.
Degenerative Changes in the Promixal Axon
Changes in the proximal part of the axon are confined to a short segment near the site of injury (Figure 1.20). If the injury is sharp and clean, the effects extend only up to one or two nodes of Ranvier proximal to the injury.
Figures 1.20A and B: (A) Schematic diagram to show neuron soon after injury (B) Degenerative changes occuring after neuronal injury
19If the injury is severe, a longer segment of the axon may be affected. The changes in the affected part are exactly the same as described for the distal part of the axon.
Transneuronal Degeneration
It is sometimes observed that changes resulting from axonal injury are not confined to the injured neuron but extend to other neurons with which the injured neuron synapses. This phenomenon is referred to as transneuronal degeneration. The degeneration can extend through several synapses (as demonstrated in the visual pathway).
Regeneration of Nerve Fibres
The regeneration of axon is a slow process and may take months. It usually begins two weeks after injury.
Macrophages remove the debris from the site of injury and Schwann cells proliferate by mitotic division to fill the gap between the promixal and distal cut ends of the axon.
In the distal stump, the Schwann cell of neurilemma divides rapidly to form numerous tubes.
The promimal axon gives off a number of fine branches (sprouts). These branches grow into the connective tissue at the site of injury in an effort to reach the distal cut end of the nerve (Figure 1.21).
When one of the regenerating axonal branches succeeds in reaching such a tube, it enters it and then grows rapidly within it. The tube serves as a guide to the growing fibre.
Axonal branches that fail to reach one of the tubes degenerate.
It often happens that more than one axonal branch enter the same tube. In that case, the largest branch survives and the others degenerate.
The axon terminal growing through the Schwann cell tube ultimately reaches and establishes contact with an appropriate peripheral end organ. Failure to do so results in degeneration of the newly formed axon.
The new axon formed in this way is at first very thin and devoid of a myelin sheath. However, there is progressive increase in its thickness, and a myelin sheath is formed around it by the Schwann cell.
From the above account, it will be clear that chances of regeneration of a cut nerve are considerably increased, if the two cut ends are near each other and, if scar tissue does not intervene between them. It has been observed that tubes formed by Schwann cells begin to disappear, if they are not invaded by axons for a long time.
Axons in the CNS do not regenerate as in peripheral nerves. However, it has been seen that if a peripheral nerve is implanted into the CNS, axons tend to grow into the nerve. This may provide a method by which regeneration of tracts could be achieved within the CNS. It appears probable that implanted peripheral nerves provide the necessary environment for regeneration of axons (which the CNS is itself unable to provide).
Factors Necessary for Satisfactory Regeneration
Chances of regeneration of a damaged nerve are better under the following conditions:
- The nerve is crushed, but there is no separation of the two ends. The endoneural sheath should be intact
- Separation of cut ends should be minimal. Scar tissue should not intervene between the two ends
- Infection should not be present.
Clinical Correlation
- Sometimes during regeneration of a mixed nerve, axons may establish contact with the wrong end organs. For example, fibres that should reach a gland may reach the skin. When this happens in the auriculotemporal nerve, it gives rise to Frey's syndrome. Instead of salivation there is increased perspiration, increased blood flow, and pain over skin.
- If the gap between the two cut ends is more, the growing axonal buds get mixed up with connective tissue to form a mass called a neuroma.
- Apart from injury, neurons may be affected by degeneration. Loss, by degeneration, of myelin sheaths can give 20rise to several conditions, the most important of which is multiple sclerosis. The condition is confined to the CNS, and peripheral nerves are spared. Symptoms include weakness and various sensory disturbances. Multiple sclerosis is believed to be an autoimmune disease.
- Prolonged pressure on a nerve can cause temporary loss of function. This can occur in unconsciousness or even in deep sleep and in bedridden patients. Pressure on the radial nerve can cause the condition known as Saturday night palsy. Pressure on blood vessels supplying a nerve can lead to a painful condition called ischemic neuritis.
NEUROGLIA
In addition to neurons, the nervous system contains several types of supporting cells called neuroglia (Figure 1.22).
Types of Neuroglia
- Astrocytes, oligodendrocytes, and microglia found in the parenchyma of the brain and spinal cord.
- Ependymal cells, lining the ventricular system.
- Schwann cells, lemmocytes or peripheral glia forming myelin sheaths around axons of peripheral nerves. It is important to note that both neurilemma and myelin sheaths are components of Schwann cells.
- Capsular cells (also called satellite cells or capsular gliocytes) that surround neurons in peripheral ganglia.
- Various types of supporting cells found in relation to motor and sensory terminals of nerve fibres.
Some workers use the term neuroglia for all these categories, while others restrict the term only to supporting cells present within the brain and spinal cord. The latter convention is used in the description that follows.
Neuroglia of Brain and Spinal Cord
Neuroglial cells present in the parenchyma of brain and spinal cord are mainly of four types:
- Astrocytes, that may be subdivided into fibrous and protoplasmic astrocytes
- Oligodendrocytes
- Ependymal cells
- Microglia.
All neuroglial cells are much smaller in size than neurons. However, they are far more numerous. It is interesting to note that the number of glial cells in the brain and spinal cord is 10–50 times as much as that of neurons. Neurons and neuroglia are separated by a very narrow extracellular space.
In ordinary histological preparations, only the nuclei of neuroglial cells are seen. Their processes can be demonstrated by special techniques.
Astrocytes
These are small star-shaped cells that give off a number of processes (Figure 1.23). The processes are often flattened into leaf-like laminae that may partly surround neurons and separate them from other neurons. The processes frequently end in expansions in relation to blood vessels or in relation to the surface of the brain. Small swellings called gliosomes are present on the processes of astrocytes. These swellings are rich in mitochondria.
Astrocytes are of two types—fibrous and protoplasmic.
- Fibrous astrocytes are seen mainly in the white matter. Their processes are thin and are asymmetrical.
- Protoplasmic astrocytes are seen mainly in grey matter. Their processes are thicker than those of fibrous astrocytes and are symmetrical.
- Intermediate forms between fibrous and protoplasmic astrocytes are also present.
The processes of astrocytes are united to those of other astrocytes through gap junctions. Astrocytes communicate with one another through calcium channels. Such communication plays a role in regulation of synaptic activity and in the metabolism of neurotransmitters and neuromodulators.
Figure 1.23: Astrocytes and macroglial cells. Note the peri-vascular feet of astrocytes forming a sleeve around a capillary
Functions
- They provide mechanical support to neurons.
- In view of their nonconducting nature, they serve as insulators and prevent neuronal impulses from spreading in unwanted directions.
- They are believed to help in neuronal function by playing an important role in maintaining a suitable metabolic environment for the neurons. They can absorb neurotransmitters from synapses, thus, terminating their action.
- They help in the formation of blood–brain barrier.
- Substances secreted by end feet of astrocytes probably assist in maintaining a membrane, the glia limitans externa, which covers the exposed surfaces of the brain. They also help to maintain the basal laminae of blood vessels that they come in contact with.
- Astroglial cells are also responsible for repair of damaged areas of nervous tissue. They proliferate in such regions (gliosis). The microglia act as macrophages to engulf and destroy unwanted material.
Oligodendrocytes
These cells are rounded or pear-shaped bodies with relatively few processes (oligo—scanty) (Figure 1.24).
These cells provide myelin sheaths to nerve fibres that lie within the brain and spinal cord. Their relationship to nerve fibres is basically similar to that of Schwann cells to peripheral nerve fibres. However, in contrast to a Schwann cell that ensheaths only one axon, an oligodendrocyte may enclose several axons.
Oligodendrocytes are classified into several types depending on the number of neurons they provide sheaths to. As a rule, oligodendrocytes present in relation to large diameter axons provide sheaths to fewer axons than those related to axons of small diameter. The plasma membrane of oligodendrocytes comes into contact with axolemma at nodes of Ranvier.
Functions
Oligodendrocytes provide myelin sheaths to nerve fibres within the CNS for fast conduction of nerve impulses.
Ependymal cells
Ependymal cells line the ventricles of the brain and central canal of the spinal cord. Ependymal cells are mainly of three types:
- Ependymocytes
- Choroid epithelial cells
- Tanycytes
The ependymocytes constitute the majority of the ependymal cells. The specialized ependymal cells in choroid plexuses (choroidal epithelial cells) secrete cerebrospinal fluid. The ependymal cells lining the floor of the fourth ventricle have long basal processes and are termed “tanycytes”.
Functions
Ependymal cells are concerned in exchanges of material between the brain and the cerebrospinal fluid at the brain-cerebrospinal fluid barrier. The blood in the capillaries of the choroid plexus is filtered through choroid epithelial cells at the blood–cerebrospinal fluid barrier to secrete cerebrospinal fluid.
Microglia
These are the smallest neuroglial cells (Figure 1.23). The cell body is flattened. The processes are short. These cells are frequently seen in relation to capillaries. As already stated, they differ from other neuroglial elements in being mesodermal in origin. They are probably derived from monocytes that invade the brain during fetal life. They are more numerous in the grey matter than in the white matter.22
Functions
They act as phagocytes and become active after damage to nervous tissue by trauma or disease. The microglia act as macrophages to engulf and destroy unwanted material.
NEUROBIOTAXIS
Origin: G. Neuro = nerve + bio = life + taxis = arrangement; literally, a law governing the arrangement of neuronal cell bodies and their fibres during life.
There are three components of this law. They are as follows:
- Neuronal cell body migrates towards the greatest density of stimuli.
- Neuronal cell body has a tendency for centralization, encephalization and telencephalization.
- Neuronal cell bodies with similar function group themselves together, and the processes with similar function run together in bundles.
Neuronal Cell Body Migrates towards the Greatest Density of Stimuli
The classical example for the first law is that of the nucleus and course of facial nerve in the brain stem. The motor nucleus of facial nerve lies in the floor of the fourth ventricle in the special visceral efferent column. As growth proceeds, the nucleus migrates at first dorsally, relative to the abducens nucleus, and then ventrally to reach its adult position. As it migrates, the axons of the nucleus elongate marking the course along which the motor nucleus of facial nerve has travelled. Facial nerve migrates dorsomedially to be in close proximity to medial longitudinal fasciculus because the latter affords a pathway for connecting fibres of facial nerve and hypoglossal nuclei to facilitate simultaneous movements of the lips and tongue in speech. Facial nerve then migrates ventrolaterally to be in close proximity to the nucleus of spinal tract of trigeminal (“the greatest density of stimuli”) to establish a quick reflex response.
The nucleus ambiguus migrates ventrolaterally towards the reticular formation of medulla oblongata. This is another example of neurobiotaxis. Nucleus ambiguus supplies the striated muscles of pharynx and larynx. The general visceral afferent fibres from the mucosa of the above organs give collaterals to the reticular formation. The nucleus ambiguus migrates towards the reticular formation (“the greatest density of stimuli”) to complete the reflex arc.
Neurons in the ventral horn of spinal cord show a specific arrangement of their cell bodies. Those that supply the trunk lie medially because they receive their greatest input from the ventral corticospinal tract in the anterior funiculus close to the medial part of ventral horn. Those neurons that supply the limbs lie laterally because they receive their greatest input from the lateral corticospinal tract.
Neuronal Cell Body has a tendency for Centralization, Encephalization and Telencephalization
The next law of neurobiotaxis states that every neuron has a tendency to centralize (to become a part of central nervous system). Those that are already centralized, tend to encephalize (to become a part of the brain). Those that are encephalized, tend to telencephalized. Telencephalization is an evolutionary process by which functions that were governed by lower centres (in lower animals) are progressively being controlled by the telencephalon (cerebrum). This process results in increased complexity of cognitive processes. Sensory neurons (located in the dorsal nerve root ganglion or sensory neurons of cranial nerves) are pulled to the periphery due to the source of stimulus. However their tendency to centralize pulls them towards the central nervous system. The most primitive sensory columns of spinal cord (fasciculus gracilis and cuneatus) terminate in the nuclei located in the medulla oblongata (the process of encephalization). Neurons located close to these neurons crossed the midline in the lower medulla and terminated in the opposite side of the spinal cord. These neurons are part of the pyramidal tract (the process of telencephalization). Pyramidal tracts still continue to cross in the lower medulla oblongata.
Neuronal Cell Bodies with Similar Function Group themselves together, and the Processes with Similar Function Run Together in Bundles
The basal lamina forming motor neurons are a group entirely anterior to the sulcus limitans. The alar lamina (sensory and integrative in function) forms another aggregation behind sulcus limitans. Some nuclei of alar lamina with dissimilar function migrate and form discrete group, for example, red nucleus, pontine nucleus, etc. However, those with similar function continue to stay close. The medial and dorsal accessory olivary nuclei lie close to inferior olivary nucleus, as all of them form climbing afferent fibres of cerebellum.
The preganglionic (connector) efferents of sympathetic nervous system are located in the lateral horn of the spinal cord just anterior to sulcus limitans. The visceral afferent neurons are also located there, just posterior to sulcus limitans. Similarly, the similarity in function of the anterior and lateral spinothalamic tracts has made them into a single, anterolateral spinothalamic tract.
In the brainstem, descending fibres form a bundle in the basal part and ascending fibres form a bundle in the tegmentum. The descending brainstem pathways that are facilitatory to flexor muscles of the body are grouped together in the lateral funiculus of the spinal cord (the corticospinal, the rubrospinal, the medullary reticulospinal). Those descending brainstem pathways 23that are facilitatory to extensor muscles of the body are grouped together in the anterior funiculus of the spinal cord (the pontine reticulospinal, vestibulospinal, tectospinal).
NEURAL STEM CELLS
Nervous tissue within the central nervous system, till recently, used to be considered as post-mitotic i.e. neurons are incapable of regeneration. However, recent research has identified cells which are capable of forming new neurons as well as glial cells in the subventricular zone of lateral ventricle and in the hippocampal gyrus. These areas are known as adult neurogenic zone. These cells which are called neural stem cells are capable of self-renewal and show plasticity. They may help in neuronal regeneration within the brain when exposed to specific neurotrophic factors but this field is still under intense research.
|
Clinical Correlation
Knowledge of anatomy is an essential prerequisite for the practice of any clinical discipline, but nowhere is this truer than in the diagnosis of neurological disorders (Table 1.5). The localisation of the areas of the nervous system involved in disease (lesion) calls for a fairly thorough knowledge of the location of various masses of grey matter, and of the courses of various tracts. The purpose of this chapter is to provide some illustrations of how knowledge of neuroanatomy can be of help in neurological diagnosis; and to introduce some terms that are commonly used in clinical practice.
In recent years, considerable advances in neurological diagnosis have become possible by the use of sophisticated imaging techniques like computed tomography (CT), and magnetic resonance imaging (MRI). In interpreting these images a thorough knowledge of the gross anatomy of the head, neck and brain (or of other regions concerned) is invaluable.
Damage to nervous tissue can occur due to various causes as listed below:
- Traumatic: Any part of the brain or spinal cord may be damaged by direct injury i.e. trauma. Apart from other obvious causes such injury may occur during child birth.
- Vascular: If nervous tissue is deprived of blood, even for a short period, irreversible damage may result. Localised damage of this kind may occur if one of the arteries supplying the brain is blocked. This may occur by clotting of blood within the vessel (thrombosis). Such an event is more likely in older individuals in whom the arteries have undergone a degenerative change known as arteriosclerosis. A vessel can also be blocked by some extraneous material (e.g., clot, fat, air) reaching it from some other part of the body through the circulation. Such matter is called an embolus. Sometimes an artery may rupture, the blood leaking into brain tissue i.e. haemorrhage causing considerable damage. A haemorrhage in the brain is often fatal. Bleeding may be caused by rupture of small abnormal dilatations of arteries (aneurysms). Aneurysms may be congenital, or may be produced due to weakening of the arterial wall in the region.
- Neoplastic: Another cause of brain damage is the presence of any abnormal mass within the cranial cavity. As the cranial cavity cannot expand, such a mass inevitably presses on brain tissue. A space occupying lesion (SOL) may be a tumour, a collection of pus, a collection of blood (in the epidural space) etc.] Apart from producing general signs of increased intracranial tension, local effects are produced depending on the area involved. Tumours of nervous tissue may be medulloblastomas or astrocytomas or oligodendromas.
- Infective: Nervous tissue may be affected by infections, both acute and chronic. An infection in the brain is referred to as encephalitis; and that in the spinal cord is called myelitis.
- Congenital malformations: Defects in neural tissue may also be caused by maldevelopment (congenital anomalies).
- Degenerative: May be due to old age or due to various metabolic disorders. Loss, by degeneration, of myelin sheaths can give rise to several conditions, the most important of which is multiple sclerosis.
- Functional: Finally, alterations in nervous function may occur in the absence of recognisable structural changes. These are called functional disorders.
Multiple Choice Questions
- The ‘Nissl substance’ represents which organelle of neuron
- Golgi complex
- Nucleolus
- Rough endoplasmic reticulum
- Mitochondria
- Bouton terminaux refers to which part of neuron
- Axon hillock
- Dendritic spine
- Internodal region
- Swelling at the end of axon
- Which of the following provides myelin sheath to the axons of the CNS?
- Astrocytes
- Oligodendrocytes
- Microglia
- Ependymocytes
- The neurons of the sympathetic ganglia are
- Multipolar
- Bipolar
- Unipolar
- Pseudounipolar
- Which of the following cells functions as the macrophage of the CNS?
- Tanycyte
- Microglia
- Oligodendrocyte
- Ependymocyte
- Which of the following is involved in ‘replacement gliosis’ following death of neurons?
- Astrocyte
- Oligodendrocyte
- Microglia
- The perivascular foot of the ‘blood–brain barrier’ is an extension from the
- Oligodendrocyte
- Ependymocyte
- Protoplasmic astrocyte
- Microglia
- Which of the following is derived from the mesoderm?
- Oligodendrocyte
- Astrocyte
- Ependymal cell
- Microglia
- Which of the following should be intact for the regeneration of an injured peripheral nerve to occur?
- Schwann cells
- Myelin sheath
- Neurilemma
- Perineurium
- Most of the primary brain tumours arise from the following EXCEPT
- Neurons
- Neuroglia
- Meninges
- Blood vessels
1. C | 2. D | 3. B | 4. A | 5. B | 6. A | 7. C | 8. D | 9. C | 10. A |