The principal functional unit of the nervous system is the nerve cell or neurone. These cells are highly specialised for the encoding, conduction and transmission of information. Neuroglial cells, or glia, are present in the nervous system in even larger numbers than neurones. Glia do not take part directly in information processing but are, nonetheless, crucial for normal neural function. Other cells are also present in the nervous system, such as those forming the walls of blood vessels but, unlike neurones and neuroglia, these are not unique to the nervous system.
The main structural features, common to all neurones, have been described briefly in Chapter 1. There are, however, numerous variations on the basic plan. The size of the cell body varies considerably, depending upon location and function. For example, some interneurones in the CNS have cell bodies as small as 5 µm in diameter, while the cell bodies of motor neurones innervating striated muscle may exceed 100 µm. The size of the cell body is usually correlated with the length of the axon. Therefore, small interneurones usually have short axons, perhaps only a fraction of a millimetre in length. At the other extreme, large motor neurones possess long axons (e.g. those passing from the spinal cord to the muscles of the foot have axons about 1 m in length).
The dendritic arborisation of neurones also shows great variation in the number, size and density of branches, which reflects the organisation of afferent inputs to the cell. For example, pyramidal cells in the cerebral cortex have one or two apical dendrites which course towards the pial surface (Fig. 2.1A) while Purkinje cells in the cerebellar cortex have highly complex, tree-like dendritic arborisations (Fig. 2.1B).
Figure 2.1 (A) A pyramidal cell in the cerebral cortex (×100). (B) A Purkinje cell in the cerebellar cortex (×90) showing the diversity of dendritic arborisations. (Golgi–Cox stain.)
The configuration of the cell body in relation to the dendrites and axon follows one of three basic patterns (Fig. 2.2). Multipolar neurones are by far the most common. Typically, they possess an axon and a number of dendrites that arise directly from the cell body. Bipolar neurones have a centrally placed cell body, from which extend a single dendrite and a single axon. Bipolar neurones occur in the afferent pathways of the visual, auditory and vestibular systems. Unipolar neurones possess a single process emerging from the cell body. This divides into dendritic and axonal branches. Neurones of this type constitute the primary afferents of spinal and some cranial nerves, having their cell bodies in the dorsal root ganglia and sensory ganglia of cranial nerves.
Figure 2.2 Unipolar, bipolar and multipolar neurones. Arrows indicate the direction of impulse conduction.
Like most other cells, neurones possess a nucleus. This is usually located in the centre of the cell body and contains the chromosomal DNA. The rest of the intracellular space is occupied by cytoplasm, which contains numerous organelles and inclusions (Fig. 2.3). Many of these are common to cells other than neurones, but some have particular prominence or significance in neurones. Numerous microscopic clumps of Nissl granules (bodies, substance) can usually be seen in nerve cell bodies stained with basophilic dyes. Nissl granules consist of rough endoplasmic reticulum and associated ribosomes. The ribosomes contain RNA (which accounts for the basophilic staining properties) and are the sites of protein synthesis. Nerve cells are highly metabolically active and, therefore, the Nissl granules are often very prominent (Fig. 2.4).
Figure 2.3 A typical neurone. The diagram illustrates the principal structural features, some intracellular organelles and the myelin sheath.
Figure 2.4 A spinal motor neurone cell body. Cresyl violet (a basophilic dye) stain shows prominent Nissl granules (×600).
Neurones contain a complex meshwork of structural protein strands called neurofilaments, which are assembled into larger neurofibrils (Fig. 2.3). They also possess a system of neurotubules that are involved in the transport of materials throughout the cell. Transport of materials occurs both away from and towards the cell body (anterograde and retrograde transport, respectively). This phenomenon is exploited in experimental neuroanatomical tracing techniques.
Some neurones contain pigment granules. Neuromelanin is a brown-black pigment produced as a by-product of the synthesis of catecholamines. Neuromelanin thus occurs most abundantly in cell groups that utilise catecholamines as their neurotransmitter, notably the pars compacta of the substantia nigra in the midbrain and the locus coeruleus in the pons. Lipofuscin is a yellow-brown pigment that accumulates in some neurones with age.
Each nerve cell is a separate physical entity with a limiting cell membrane. In order for information processing to occur in networks of neurones, therefore, information has to pass between neurones. This occurs at synapses. The basic structure of the synapse has been outlined in Chapter 1. The most common location for synapse formation is between the terminal axonal arborisation of one neurone and the dendrite of another (axodendritic synapse). Other locations are also possible and they give axosomatic, axoaxonal and dendrodendritic synapses. Neurotransmission between neurones occurs by release of specific chemical agents from the presynaptic ending that act upon receptors in the postsynaptic membrane.
Neurotransmitter (transmitter) chemicals are stored in vesicles within the presynaptic ending. A single neurone is thought to release the same transmitter at all its synapses, and all neurones of a particular type, in terms of origin, termination and function, utilise the same transmitter. Numerous transmitter substances have been identified at various sites in the nervous system. It has long been known that acetylcholine(ACh) is the transmitter between motor neurones and striated muscle. It is also the transmitter at autonomic ganglia and is released by postganglionic parasympathetic neurones. Some amino acids act as neurotransmitters. The most important are glutamic acid (glutamate) and gamma-aminobutyric acid (GABA) which occur widely and are the principal excitatory and inhibitory transmitters, respectively, in the CNS. Several monoamines are important transmitters. Noradrenaline (norepinephrine) is released by postganglionic sympathetic neurones peripherally as well as at some sites within the CNS. Dopamine and serotonin (5-hydroxytryptamine, 5-HT) also act as transmitters in the brain and spinal cord.
The effect of the neurotransmitter must be terminated once it has acted upon the postsynaptic membrane. This is achieved either by enzymic destruction of the transmitter or by its re-uptake into nerve endings and glia. For example, at the neuromuscular junction (see Fig. 3.6) and those neurone/neurone synapses where acetylcholine acts as transmitter, its action is terminated by the enzyme acetylcholinesterase(AChE). In contrast, monoamine- and amino acid-mediated transmission are usually terminated by a re-uptake mechanism.
A number of peptides (neuropeptides) are stored and released at synapses. These include enkephalin, substance P, cholecystokinin, somatostatin, dynorphin and others. These peptides are often found co-localised in the same neurones as amino acid or monoamine neurotransmitters and are sometimes called co-transmitters. It is believed that the neuropeptides modulate the release, re-uptake and postsynaptic effects of other transmitters and they are, therefore, often referred to as neuromodulators.
The neurone is the principal functional unit of the nervous system, specialised for the receipt, processing and transmission of information.
Great variability exists in the size and shape of nerve cell bodies, their dendritic arborisations and axons, which reflects their functional specialisation.
Nerve cells contain a number of organelles and inclusions. Among these are Nissl granules, neurofilaments and neurotubules, and pigment granules.
A large number of neurotransmitter substances are known that mediate transmission between neurones. These include primarily acetylcholine, various amino acids (GABA, glutamate) and monoamines (dopamine, noradrenaline (norepinephrine) and serotonin).
Peptide neuromodulators are co-localised with other transmitters in many neurones.
Neuroglia are not directly involved in information processing but they are crucial for normal functioning of the nervous system. Various types of neuroglial cell are recognised: principally astrocytes, oligodendrocytes (oligodendroglia) and microglia.
Astrocytes possess numerous processes. Some of these form so-called ‘perivascular endfeet’ upon the walls of blood capillaries (Fig. 2.5). Astrocytes are probably involved in the exchange of chemicals between the circulatory system and nervous tissue. It has been suggested that they constitute the ‘blood–brain barrier’, which restricts the access of circulating chemicals to the brain and spinal cord.
Figure 2.5 An astrocyte showing a process forming a perivascular endfoot on a blood capillary. Cajal’s gold chloride stain (×180).
Oligodendrocytes possess few processes. Their main role is production of the myelin sheath that surrounds many axons in the CNS. Schwann cells perform this function in the peripheral nervous system. At any point along the length of a myelinated axon the myelin sheath is comprised of numerous concentric layers of the cell membrane of a single oligodendrocyte or Schwann cell (Fig. 2.6A). Each glial cell produces the myelin sheath over only a short segment of axon (up to about 1 mm). A long axon is, therefore, enveloped by the membranes of many glial cells. Adjacent segments of myelin, derived from different glial cells, are separated by a small gap, the node of Ranvier(Fig. 2.3). Unmyelinated axons also have a close association with glial cells but several axons usually share a single glial cell (Fig. 2.6B).
Figure 2.6 (A) Transverse section through a myelinated axon, illustrating the structure of the myelin sheath. (B) Unmyelinated axons.
In myelinated axons, ionic fluxes across the axonal membrane, which mediate generation of the action potential, occur only at the nodes of Ranvier where the axon is exposed to the extracellular space. Between nodes, where the axon is insulated by myelin, depolarisation spreads by passive means (electrotonus). This mode of propagation of action potentials in myelinated axons is known as saltatory conduction (Latin: saltare, to jump), since the action potential may be thought of as ‘jumping’ from node to node. It is considerably faster than conduction in unmyelinated axons.
Neuronal and glial disorders
Once development has been completed, individual neurones no longer replicate, but they do undergo continual repair to maintain their integrity. Hence, they are prone to neurodegenerative diseases, which in childhood and youth are often genetically determined and in the elderly are sporadic. Glia, unlike neurones, are capable of replication and they are, therefore, susceptible to neoplasia. Consequently, most brain tumours are gliomas and not tumours of neurones themselves. According to the cell of origin, they may become either oligodendrogliomas or astrocytomas. Microglia form part of the immune system and may proliferate to become cerebral lymphomas.
The myelin sheath of neuronal axons can be the seat of inflammatory diseases. In Europe and North America, the most common immune disorder of the CNS is multiple sclerosis, which leads to episodes of demyelination and remyelination of axons, corresponding to relapses and remission of neurological signs and symptoms. Since the disorder is chiefly of axons, not cell bodies, magnetic resonance (MR) brain imaging can detect abnormal signals from demyelinating foci in the cerebral white matter.
Neuroglia are important for normal neural function because of their ancillary roles.
Astrocytes possess long processes that form perivascular endfeet around blood capillaries. They are involved in the transfer of materials between the vascular system and neural tissue.
Oligodendroglia give rise to the myelin sheath surrounding axons in the CNS. Schwann cells form myelin in the peripheral nervous system.
Microglia have a phagocytic role in injury to the nervous system.
Microglia are small cells with few processes. Microglia increase in number at sites of damage in the CNS and have a phagocytic role, similar to macrophages elsewhere. The ependyma consists of epithelial cells, which line the ventricles and cover the choroid plexus.