The majority of neurons have only one axon, although a very few have no axon at all. The axon varies in length according to neuronal needs- it often correlates with cell body size. The axons of inter-neurons found in the CNS may have cell bodies of diameter only 5μ, and an axon of less than a millimetre in length, whilst the spinal motor neurons serving the foot can have cell bodies of 100μ in diameter, and can extend for up to a metre long! Neurofilament numbers are also in proportion with axonal diameter; it is possible that the filaments determine the axonal diameter.
All neurons have a membrane potential, due to unequal ion concentrations on either side of the membrane, which can move down their concentration gradients through ions channels and pores. The ion inequilibrium is maintained at a resting potential by the presence of ATP-utilising pumps, which restore the gradients.
The action potential in most nerve cells is caused by a transitory increase in sodium conductance, which drives the membrane potential towards that of the sodium equilibrium potential (about +68mV for most peripheral membranes), followed by an increase in potassium conductance that returns the membrane potential to its resting level (period known as repolarisation).
Neurons synapse with other neurons, or with an endplate in the case of motor neurons, glands etc. Synapses are necessary in order for neurons to pass information between themselves in a network. Synapses may be axo-dendritic (most common), axo-somatic and (rarely) axo-axonal and dendro-dendritic.
Axodendritic synapses are usually excitatory in their effect upon target neurons, whereas most axosomatic synapses have an inhibitory effect.
Most synapses are chemical, that is, the axon terminal (pre-synaptic) releases a chemical substance known as a neurotransmitter across the synaptic cleft, to act upon another neuron or an effecter cell. By inducing changes in its electrical conductivity to certain ions, the post-synaptic membrane may then allow another impulse to be generated (or an effect to be mediated if non-neuronal). The actions of neurotransmitters are not confined to ionic conductances, however. Chemical mediators in the brain can produce effects on transmitter synthesis and expression of neurotransmitter receptors also.
Neurotransmitters are stored in high concentrations within vesicles in the pre-synaptic bouton. The same neurotransmitter is released from all axon terminals of a single neuron, and all similar neurons (ones with the same origin, function or location) use the same neurotransmitter too.
Acetylcholine is a ubiquitous transmitter, released at synapses between motor neurons and striated muscle, at autonomic ganglia, and by post-ganglionic parasympathetic neurons. Other neurotransmitters may be amino acids (GABA, glutamate); or monoamines (noradrenaline, dopamine, serotonin); peptides (enkephalin, substance P, cholecystokinin, somatostatin, dynorphin)- peptides are often found as co-transmitters, so are known as neuromodulators.
Neurotransmitters may be broadly divided into two types: fast neurotransmitters, which operate through ligand-gated ion channels (e.g. glutamate, GABA) and slow neurotransmitters, which operate mainly through G-protein-coupled receptors (e.g. dopamine, neuropeptides). There are also numerous other neuromodulators (such as NO and arachidonic acid metabolites) that may be produced by non-neuronal cells too, and other mediators (cytokines, chemokines, growth factors, steroids) that perhaps control long-term changes in the brain (synaptic plasticity, remodelling), by affecting gene transcription.
Although most synapses are chemical, as described, some cell synapses conduct impulses directly through gap junctions- these are known as electrical synapses.
The principal mechanism of transmitter release in both the peripheral and central nervous systems (and also in many hormone-secreting cells) is exocytosis, initiated by the arrival of an action potential along the axon. The action potential depolarises the membrane, thus opening voltage-gated calcium channels, increasing the amount of calcium entering the cell. This increase in pre-synaptic intracellular calcium has been identified as being directly responsible for the release of transmitter, and much of the evidence for this mechanism comes from work by Katz and from rapid-freeze electron microscopy.
Once synaptic vesicles have become loaded with transmitter, they attach themselves to docking sites located inside the synaptic membrane facing the synaptic cleft. These sites are closely associated with calcium channels, which allows optimum placement for release of their stored transmitter once calcium has entered the terminal. Once empty, the redundant vesicle is recaptured by endocytosis, and fuses with the larger endosomal membrane. It is from this endosome that the new vesicles are budded off from, and new transmitter is uptaken from the cytosol using specific transport proteins. This next generation of vesicles then dock to the membrane in the same positions as before, and the cycle repeats. The proteins involved in docking are known as SNARES.
So how does calcium influx induce the vesicles to liberate their neurotransmitter? Well, it has been shown that there exist various proteins within the nerve terminal that are homologous to those found to be involved in Golgi secretion. Since it was thought that the same basic mechanism might underlie both processes, the proteins were analysed further.
It is believed that a protein known as synaptotagmin is the major sensor for calcium release, and that its activities are calcium-level dependent. In knockouts, evoked release is severely reduced or diminished, although there is an increase in spontaneous release. Thus, it appears that in the absence of calcium, synaptotagmin prevents vesicular fusion, and once calcium influx occurs, may stimulate it.
The botulinum and tetanus neurotoxins released by Clostridium bacteria act by interfering with this system. Tetanus toxin prevents the release of glycine (an inhibitory neurotransmitter found in the spinal cord). The result is that motor neurons go out of control, leading to prolonged, agonizing spasms- especially those involved with the facial, jaw and spinal muscles. The spasms may be so strong, that about half the patients who display these tetanus symptoms die of exhaustion within a few days.
By definition, neurons need to form a network. One nerve cell cannot receive, analyse or transmit information if it does not synapse with something suitable, be it an endplate or another neuron.
Even a complex of inter-connecting neurons could not be wholly efficient or useful, as it has been shown that neuroglia (literally, ‘nerve glue’) are paramount for normal functioning of the nervous system. When discussing cells of the nervous system, I think it is necessary to include both neurons and neuroglial cells.
Although not directly involved in the information transfer, the five different types of neuroglial cell (astrocytes, oligodendrocytes, Schwann cells, ependymal cells, and microglia) all have specific roles to play.
Astrocytes are star-shaped cells, due to their numerous radiating processes. They originate from the neural tube, and are located in the CNS. They probably comprise the blood-brain barrier, as one type of astrocyte can develop expanded end-feet which link to endothelial cells by occluding junctional complexes (similar to those found in tight epithelia).
Astrocytes retain the ability to proliferate when the CNS is damaged, generating scar tissue. An important role of astrocytes is the regulation of CNS functions, and its chemical and ionic environment. It has been found that astrocytes in vitro show adrenergic receptors, amino acid receptors (e.g. GABA), and peptide receptors (AT II). This feature allows astrocytes to respond to several different stimuli. They also have the ability to release metabolic substances and neuroactive molecules themselves, which means their role in neuronal survival is not to be underestimated, especially since one of the neuroactive molecules is known to be the potentially neurotrophic somatostatin.
Their effects reach to other glial cells too, as they are linked via gap junctions, allowing astrocytes to interact with oligodendrocytes to influence myelin turnover, for example.
Brain tumours most commonly originate from neuroglial cells, and in particular from astrocytes. This is due to the ability of glia to replicate (unlike neurons), and so are susceptible to neoplasia.
Oligodendrocytes are neural tube-derived cells responsible for producing the myelin sheath that surrounds some neuronal axons, and provides electrical insulation and thus faster impulse propagation.
Schwann cells have the same origin and role as oligodendrocytes, but are found surrounding axons in the PNS. With Schwann cells, one cell forms myelin around one axon, whilst oligodendrocytes have the ability to branch and serve more than one neuron at a time.
Ependymal cells are low columnar ciliated epithelial cells that line the ventricular system of the brain. Cilia present on their free surface help to propel CSF through the ventricles.
Microglia are small, elongated cells with short irregular processes. They are derived from bone marrow precursor cells, and are the nervous equivalent of phagocytic cells. In the adult CNS, microglia are responsible for inflammation and repair.
