Professor G. G. Lunt, Dept of Biology and Biochemistry, University of Bath, on 6 September 2000

Towards the end of the 19th century a consensus had been reached on the detailed organisation of the nervous system. It was believed that, unlike other organs, the brain was not made up from discrete cells but that it was a continuum, a network of criss-crossing fibres, and at the points where the fibres crossed there were thickenings _ the neurones. The reticular (network) theory was challenged by Santiago Ramon y Cajal, a Spanish microscopist, who examined multiple brain sections and noted that the many fibres approached very closely to the neurones but they were not in fact continuous with them. Thus the brain was made up from numerous discrete cells each of which had long projections, and these projections approached very closely neighbouring cells but were not physically connected to them. The scientific community of the day dismissed Cajal's findings and he found it increasingly difficult to get a proper hearing for his new ideas on brain structure.
At this time the English electrophysiologist, Sir Charles Sherrington showed that electrical impulses propagated at uniform velocity along these fibres within the brain but the transmission of the electrical signal to another neurone was slow. Sherrington realised that this electrical discontinuity may well be the functional counterpart of the structural discontinuity described by Cajal. The two scientists began to collaborate and jointly realised that the gaps in the nerve network were areas of potential control of transmission. They coined the term synapse to describe the gap between the end of the transmitting fibre and the receiving fibre. Their ideas were soon accepted and the reticular hypothesis was consigned to history.
The application of electron microscopy to biological material in the 1960s revealed further details of the structure of neurones and synapses. Neurones were seen to have two types of fibre: input (`short') fibres of which there are a large number, and output (`long') fibres, called axons, of which there is generally only one, sometimes a few. These axons have special `vesicles' in bags at the end of them which release the chemical message or transmitters which relay the message across the discontinuity of the synapse.
The neurone contains and is surrounded by a water-based cellular fluid containing sodium (+), potassium (+) and chlorine (-) ions which result in a negative charge of 60 mV existing inside, compared to outside the cell. Changes in the composition can vary this potential. Receptors in the cell wall allow gradual migration of these chemicals in and out when the cell is subjected to a stimulus, which might be light, pressure or other stimuli, depending on the function of the neurone. When the accumulated potential reaches -20 mV the output `fires' as the cell wall resistance falls, but when the potential reaches +40 mV the resistance rises again. The magnitude of the output current is constant but the frequency at which it `fires' varies to provide a different strength of signal to the vesicle. This firing constitutes the action potential or nerve impulse and is the form in which information is passed around the nervous system.
Thus at one level the neurone has a specialised but rather simple electrical activity _ it is said to be electrically excitable, that is the summated electrical inputs, the flow of ions in and out of the cell, determine whether or not the neurone `fires'. The complexity and sophistication of the nervous system derives from the incredibly large number of synapses and therefore the incredibly large number of potential electrical inputs the neurone receives. It is the summated and integrated inputs that determine whether or not the neurone responds. The number of neurones and their multiplicity of connections provide multiple options for onward transmission or modifications or termination of electrical signals.
This multiplicity of connections is one thing that is 'so special about neurones'; the brain is not more than the sum of its parts, it is the sum of its extraordinarily high number of parts and connections. These connections are `fluid', unlike a computer. The nervous systems of simple animals have the same rather small number of neurones in the same anatomical location but the pattern of connections is highly variable, because each animal will have had different experiences of its environment and will have adapted the connectivity to respond to those differences. Cajal had noted that as the brain developed what changes most is not the number of neurones but the number of synapses. This adaptive response is another thing that is so special about neurones. Identical (cloned) daphnia all have the same neurones but the connectivity between them is different.
There is another level of regulation at the synapse, but that is another story, which will be told in a later lecture in this series. (see Drugs and the Brain).
G .G. Lunt
The questions were mostly about the transmission of messages and the synapse. During brain formation, the synapses are formed at random; those that are used live, those not used die. This may be an explanation of addiction. Synapses are not regularly spaced, they tend to cluster on the input fibres and there is no evidence that a signal has an `address code'. Synapse action is not necessarily quick, it can take hours, as is demonstrated by experimentally wearing `upside down' glasses, when the brain takes 24 hours to adjust.
A `gifted' child may have more neurones; the number is not the same for every person. The connections are genetically programmed, e.g. motor neurones to muscles, but then there is randomness and redundancy. The pattern of use is important.
Axons can divide and go to more than one receptor neurone, so one neurone can send a message to many others, but a retinal receptor, for example, will only connect to the visual area of the brain.
Blood replaces the ions in and around the neurones, which also need glucose and oxygen to survive.
A vote of thanks was proposed by Roger Cloet and passed with acclamation.
Don Lovell