Neurones have three highly specialised structures, which are essential for communication between these cells:
The axon membrane is polarised and can exist in two electrical states:
At rest, the axon is polarised and has a resting membrane potential of around -70mV (inside the axon with respect to the outside). When the neurone becomes active, it generates APs, during which the membrane potential reverses, and may reach +40mV (again, inside the axon).
Each action potential lasts about 1 msec, and the frequency of APs is an essential method of coding information carried over long distances.
Communication occurs at spectacular speed due to the conduction of trains of action potentials (APs) along the length of the axonal membrane.
During the action potential, a small number of sodium ions enter the axon when voltage-gated sodium channels in the membrane open as a result of depolarisation.
The action potential moves along the axonal membrane because local circuits are set up which cause depolarisation of the adjacent axonal membrane; this depolarisation causes voltage-gated sodium channels to open in the surrounding membrane. The current flow through these local circuits is shown in the top left of the illustration opposite.
The conduction velocity is a measurement of the speed at which the AP travels along the axonal membrane. The largest axons transmit APs at around 100 metres/second. Consequently it takes about 10 msec for an AP to travel along 1 m of axon.
The highest conduction velocities are achieved by having a myelin sheath wrapped around the axon; myelin consists of many compacted layers of glial cell membrane produced by Schwann cells (in peripheral nerves) and Oligodendrocytes (within the CNS).
In myelinated axons, Schwann cells wrap many layers of lipid membrane around the axon, and the junctions between these Schwann Cells are known as Nodes of Ranvier.
Because the myelin has a very high electrical resistance, the current flow follows the line of least resistance and jumps from node to node.
Saltatory Conduction is the name given to the speeding up of the conduction velocity - a consequence of the presence of myelin, whcih causes the action potential to jump from node to node.
When action potentials arrive at the nerve terminal, the vesicles in the nerve ending release their neurotransmitter, close to the surface of dendrites of another neurone.
Neurotransmitters combine with specialised receptor molecules in the membrane of post-synaptic cells.
in the pre-synaptic terminal, voltage-gated calcium channels open when an action potential invades the nerve terminal, causing calcium ions to move into the terminal.
Calcium entry causes vesicles containing neurotransmitter to fuse with the pre-synaptic membrane and release their contents.
Once released the neurotransmitter is commonly taken up again into the nerve terminal, or into adjacent glial cells.
In the CNS, the commonest neurotransmitters are glutamate and GABA, both of which are converted to glutamine within astrocytes; the glutamine is passed into nerve endings, and is the substrate that is used in the synthesis of both transmitters.
Neurotransmitters can alter the activity of post-synaptic neurones; excitatory transmitters depolarise the cell membrane and increase the frequency of firing, and inhibitory transmitters hyperpolarise the membrane and decrease the activity of the post-synaptic cell.
These changes are the result of combination of a neurotransmitter molecule with a specific receptor protein on the dendrites of the post-synaptic neurone.
The main excitatory transmitter in the CNS is glutamate: is is synthesised in the nerve ending from glutamine and is concentrated in synaptic vesicles.
The main inhibitory transmitters in the CNS are Gamma-Amino-Butyric Acid (GABA) and Glycine.
GABA has a major role to play within the brain, while glycine is particularly important in the spinal cord.
Neuropeptides often coexist along with the other transmitters within the same neurone, and co-transmission has been demonstrated in some synapses.
The simplest neural network, the stretch reflex, consists of a chain of only two neurones in series: muscle spindle afferents make contact with alpha-motoneurones innervating the same muscle.
The networks involved in withdrawal of a limb following a potentially injurious stimulus are more complex and involve many interneurones within the spinal cord.
Other networks utilise connections between the spinal cord and the brainstem; an example is the vestibulo-spinal system concerned with maintenance of balance.
All networks involve a combination of excitatory and inhibitory influences, and the balance between them can change.
Many networks make use of sensory receptors to provide feedback. Other networks, central pattern generators, can generate rhythmic movements that occur in the absence of sensory feedback.
The axon can be long - up to 50000 cell diameters in length, have many branches, and contain >90% of the cytoplasm of the cell.
In order for the distant parts of an axon to be kept alive, chemicals produced by the cell body, such as the proteins necessary for neurotransmission, are transported along the cytoskeleton of the axon using a slow process called axoplasmic transport.
Essential materials are packaged within vesicles that travel along the cytoskeleton in the interior of the axon at rates of up to 40 mm/day.
Transport of materials from cell body to nerve terminals is called anterograde axonal transport, and from nerve terminals to the cell body - retrograde axonal transport.
Retrograde transport informs the neuronal nucleus about the state of the nerve endings and the integrity of synaptic function. Nerve growth factor and other neurotrphins are produced by tissues and retrogradely transported to inform the nucleus about the integrity of the synapse.
If axons are injured, the terminal section of peripheral axons can form new branches (sprouting) and reconnect with the follower cell. Axonal transport carries newly synthesised materials to the regenerating nerve endings.
When an axon is transected, the terminal portion of the axon degenerates (Wallerian Degeneration), and the central end begins to regrow.
The growing end of this regenerating axon is known as the growth cone. The neurone synthesises more structural proteins.
The changes in the body of the neurone include marked changes to the Nissl substance, and are described as Chromatolysis.
The growing sprouts of the axons may reconnect with their target organ. Alpha motoneurone terminals can sprout and reinnervate denervated muscle fibres, resulting in an increase in the size of motor units.
In the CNS, such regeneration is rarely successful, and the loss of synaptic inputs can cause post-synaptic neurones to degenerate or atrophy or show functional changes.
Adult neurones are largely incapable of mitosis. However there are a few sites in the CNS where new neurones can be produced from stem cells: these include the sub-ventricular zone (SVZ) of the hypothalamus, the hippocampus and cerebellum in most mammalian species.
Neurodegenerative Diseases are diseases that result in the progressive death of neurones. These include Alzheimer's Disease, Parkinson's Disease and Motoneurone Disease, which involve intracellular pathology within neurones in the cerebral cortex, the substantial nigra and motoneurones/spinal cord respectively.
Neurones within the brain of patients with neurodegenerative disorders often show intracellular inclusions, some of which consist of abnormal molecules. One example is the accumulation of extracellular insoluble beta-amyloid in Alzheimer's Disease.
Amyloid Protein Precursor (APP) is a normal protein in many neurones, and Alzheimer's Disease is characterised by the extracellular accumulation of a polymer called beta-amyloid, which occupies space between cells in the CNS, and contributes of neuronal degeneration.
Other pathological changes include the neurofibrillary tangles in Alzheimer's Disease and Lewy Bodies in Parkinson's Disease.
Inclusion bodies also occur within the nuclei of neurones in patients with Huntington's Disease, an inherited disorder that affects the basal ganglia, cerebellum.