Matt Ridley on Learning and Memory

Human beings are machines designed to be modified by experience.

What is learning? What changes occur to nerve cells when the brain acquires a new habit or a change in its behaviour? The central nervous system consists of lots of nerve cells, down each of which electrical signals travel; and synapses, which are junctions between nerve cells. When an electrical nerve signal reaches a synapse, it must transfer to a chemical signal, like a train passenger catching a ferry across a sea channel, before resuming its electrical journey. Learning seems to be a change in these properties. Thus when the seas slug Aplysia habituates to a false alarm, the synapse between the receiving, sensory neuron and the neuron that moves the gill is weakened. Conversely, when the sea slug is sensitised to the stimulus (by a shock distributed before the a jet of water is applied), the synapse is strengthened.

Gradually and ingeniously, Kandel and his colleagues homed in on a particular molecule in the sea-slug brain which lay at the heart of this weakening or strengthening of the synapses. The molecule is called cyclic AMP.

Kandel had discovetred a cascade of chemical changes all centred around cyclic AMP. Ignoring their names, imagine a string of chemicals called A, B, C and so on:

A makes B,
Which activates C,
Which opens a channel called D,
Thus allowing more E into the cell,
Which prolongs the release of F,
Which is the neurotransmitter that ferries the signal across the synapse to the next neuron.

Now it so happens that C also activates a protein called CREB by changing its form. Animals that lack the activated form of CREB can still learn things but cannot remember them for more than an hour or so. This is because CREB, once activated, starts switching on genes and thus altering the very shape and function of the synapse. The genes thus alerted are called CRE genes, which stands for cyclic AMP response elements (Kandel).

In Drosphila, mutants like dunce, cabbage, amnesiac, rutabaga, radish and turnip (numbering in all some seventeen learning mutations in all) all show deficits in making or responding to cyclic AMP (Tully).

One could image CREB as a master gene of learning that switches on and off other genes.

The quest to understand learning is in fact a genetic quest.

In humans CREB is located at chromosome 2.

Deep in the base of the brain lies a structure called the hippocampus (Greek for seahorse) and a part of the hippocampus is called the Ammon's horn (after the Egyptian god associated with the ram). In Ammon's horn, in particular, there are a large number of 'pyramidal' neurons which gather together inputs of other, sensory neurons. A pyramidal neuron is difficult to 'fire', but if two separate inputs arrive at once their combined effect will cause it to fire. Once it fires, it is much easier to fire again but only by one of the two inputs that originally fired it, and not by another input. Thus the sight of a pyramid and the sound of the word Egypt van combine to fire a pyramidal cell, creating an associative memory between the two.

Memories, however, do not reside in the hippocampus, but in the neocortex. What resides in the hippocampus is the mechanism for creating a new long-term memory.

HM had a chunk of his brain (the medial temporal lobe) removed to prevent epileptic seizures caused by a bicycle accident. He cannot form new long-term memories but the memory of his childhood is still intact.

HM can learn new tasks well, but cannot remember that he has learnt it (i.e. procedural memory is intact whereas declarative memory is impaired).

Neuroscientists have gradually narrowed down the search for the most vital of all memory organs to one principal structure, the perirhinal cortex. It is here that sensory information, sent from the visual, auditory, olfactory or other areas, is processed and made into memories, perhaps with the help of CREB. The information is then passed to the hippocampus and thence to the diencephalon for temporary storage. If it is deemed worthy of permanent preservation it is sent back to the neocortex as a long-term memory: that strange moment when you suddenly don't need to keep looking up somebody's telephone number but can recall it.