Study guidelines
- 1.
Discuss the challenge faced by many neurons in having to deliver and retrieve materials over enormous distances, and the economy of transmitter recycling at nerve endings.
- 2.
Give an example of how a healthy transport system can spread disease in the nervous system.
- 3.
Describe the lock and key analogy used in pharmacology.
- 4.
Draw an axodendritic synapse, and then add another axon dividing to exert both presynpatic and postsynaptic inhibition.
- 5.
Explain how a demyelinating disorder can compromise conduction.
- 6.
Draw up a structure–function list for neuroglial cells.
- 7.
Gliomas will obviously interfere with brain function in the region they grow. Explain how they may exert effects at a ‘distance’.
Nerve cells, or neurons , are the structural and functional units of the nervous system. They generate and conduct electrical changes in the form of nerve impulses. They communicate chemically with other neurons at points of contact called synapses . Neuroglia (literally, ‘nerve glue’) is the connective tissue of the nervous system. Neuroglial cells are as numerous as neurons in the brain. They have important nutritive and supportive functions.
Neurons
Billions of neurons form a shell, or cortex , on the surface of the cerebral and cerebellar hemispheres. In this general context, nuclei are aggregates of neurons buried within the white matter.
In the central nervous system (CNS), almost all neurons are multipolar, their cell bodies or somas having multiple poles or angular points. At every pole but one, a dendrite emerges and divides repeatedly ( Figure 6.1 ). On some neurons the shafts of the dendrites are smooth; on others the shafts show numerous short spines ( Figure 6.2 ). The dendrites receive synaptic contacts from other neurons, some on the spines and others on the shafts.
The remaining pole of the soma gives rise to the axon , which conducts nerve impulses. Most axons give off collateral branches ( Figure 6.3 ). Terminal branches synapse on target neurons.
Most synaptic contacts between neurons are either axodendritic or axosomatic. Axodendritic synapses are usually excitatory in their effect on target neurons, whereas most axosomatic synapses have an inhibitory effect.
Internal structure of neurons
All parts of neurons are permeated by microtubules and neurofilaments ( Figure 6.4 ). The soma contains the nucleus and the cytoplasm or perikaryon ( Gr. ‘around the nucleus’). The perikaryon contains clumps of granular endoplasmic reticulum known as Nissl bodies ( Figure 6.5 ), as well as Golgi complexes, free ribosomes, mitochondria, and smooth endoplasmic reticulum (SER) ( Figure 6.4 ).
Intracellular transport
Turnover of membranous and skeletal materials takes place in all cells. In neurons fresh components are continuously synthesised in the soma and moved into the axon and dendrites by a process of anterograde transport . At the same time, worn-out materials are returned to the soma by retrograde transport for degradation in lysosomes (see also target recognition, later).
Anterograde transport is of two kinds: rapid and slow. Included in rapid transport (at a speed of 300-400 mm/day) are free elements such as synaptic vesicles, transmitter substances (or their precursor molecules), and mitochondria. Also included are lipid and protein molecules (including receptor proteins) for insertion into the plasma membrane. Included in slow transport (at 5-10 mm/day) are the skeletal elements and soluble proteins, including some of those involved in transmitter release at nerve endings. Microtubules seem to be largely constructed within the axon. They are exported from the soma in preassembled short sheaves that propel one another along the initial segment of the axon; further progress is mainly by a process of elongation (up to 1 mm apiece) performed by the addition of tubulin polymers at their distal ends, with some disassembly at their proximal ends. The bulk movement of neurofilaments slows down to almost zero distally; there, the filaments are refreshed by the insertion of filament polymers moving from the soma by slow transport.
Retrograde transport of worn-out mitochondria, SER, and plasma membrane (including receptors therein) is fairly rapid (150-200 mm/day). In addition to its function in waste disposal, retrograde transport is involved in target cell recognition. At synaptic contacts, axons constantly ‘nibble’ the plasma membrane of target neurons by means of endocytotic uptake of protein-containing signalling endosomes. These proteins are known as neurotrophins (‘neuron foods’). They are brought to the soma and incorporated into Golgi complexes there. In addition, the uptake of target cell ‘marker’ molecules is important for cell recognition during development. It may also be necessary for viability later on because adult neurons shrink and may even die if their axons are severed proximal to their first branches.
The longest-known neurotrophin is nerve growth factor, on which the developing peripheral sensory and autonomic systems are especially dependent. Adult brain neurons synthesise brain-derived neurotrophic factor (BDNF) in the soma and send it to their nerve endings by anterograde transport. Animal studies have shown that BDNF maintains the general health of neurons in terms of metabolic activity, impulse propagation, and synaptic transmission.
Transport mechanisms
Microtubules are the supporting structures for neuronal transport. Microtubule-binding proteins, in the form of ATPases, propel organelles and molecules along the outer surface of the microtubules. Distinct ATPases are used for anterograde and retrograde work. Retrograde transport of signalling endosomes is performed by the dynein ATPase . Failure of dynein performance has been found in motor neuron disease, described in Chapter 16 .
Neurofilaments do not seem to be involved in the transport mechanism. They are rather evenly spaced, having side arms that keep them apart and provide skeletal stability by attachment to proteins beneath the axolemmal membrane. Neurofilament numbers are in direct proportion to axonal diameter and may in truth determine axonal diameter.
Some points of clinical relevance are highlighted in Clinical Panel 6.1 .
Tetanus
Wounds contaminated by soil or street dust may contain Clostridium tetani , which produces a toxin that binds to the plasma membrane of nerve endings, is taken up by endocytosis, and is carried to the spinal cord by retrograde transport. Other neurons upstream take in the toxin by endocytosis—notably Renshaw cells ( Chapter 15 ), which normally exert a braking action on motor neurons through the release of an inhibitory transmitter substance, glycine . Tetanus toxin prevents the release of glycine. As a result, motor neurons go out of control, particularly those supplying the muscles of the face, jaws, and spine; these muscles exhibit prolonged, agonising spasms. About half of the patients who show these classic signs of tetanus die of exhaustion within a few days. Tetanus is entirely preventable by appropriate and timely immunisation.
Viruses and toxic metals
Retrograde axonal transport has been blamed for the passage of viruses from the nasopharynx to the central nervous system (e.g. herpes simplex virus) and also for the uptake of toxic metals such as lead and aluminium. Viruses, in particular, may be spread widely through the brain by means of retrograde transneuronal uptake.
Peripheral neuropathies
Defective anterograde transport seems to be involved in certain ‘dying back’ neuropathies in which the distal parts of the longer peripheral nerves undergo progressive atrophy.
Synapses
Synapses are the points of contact between neurons.
Electrical synapses
Electrical synapses are scarce in the mammalian nervous system. They consist of gap junctions (nexuses) between dendrites or somas of contiguous neurons, where there is cytoplasmic continuity through 1.5-nm channels. No transmitter is involved, and there is no synaptic delay. They permit electrotonic changes to pass from one neuron to another. Being tightly coupled, modulation is not possible. Their function is to ensure synchronous activity of neurons having a common action. An example is the inspiratory centre in the medulla oblongata, where all the cells exhibit synchronous discharge during inspiration. A second example is among neuronal circuits controlling saccades , where the gaze darts from one object of interest to another.
Chemical synapses
Conventional synapses are chemical, depending for their effect on the release of a transmitter substance. The typical chemical synapse comprises a presynaptic membrane , a synaptic cleft , and a postsynaptic membrane ( Figure 6.6 ). The presynaptic membrane belongs to the terminal bouton, the postsynaptic membrane to the target neuron. Transmitter substance is released from the bouton by exocytosis, traverses the narrow synaptic cleft, and activates receptors in the postsynaptic membrane. Underlying the postsynaptic membrane is a subsynaptic web , in which numerous biochemical changes are initiated by receptor activation.
