The long and short of it

14/04/1996
Down To Earth

The long and short of it FORTY-ONE year old Tully ofCold Spring Harbour Laboratory, New York, us, bears an uncommon epithet: the lord of the flies. Sitting for hours together in a dark closet which resounds to the buzzing of hundreds of flies is the way, according to Tully, to unravel~ne of the least understood mysteries of life -the mechanism of memory.

M~mory can be broadly divided into two types: long-term and short-term. Tully is primarily concerned with long- term memory, which fades away with natural aging and might collapse alto- gether owing to brain disorders like the Al,?heimer'sdisease. Late last year,Tully and his team of researchers showed for the first time that it is possible to enhance long-term memory of fruitflies {Drosophila melanogaster) through genetic manipulation.

Tully, in his study, used a self- designed instrument which allowed him "to measure the learning capacity of the flies". The instrumentgavea mild electric &hock to the flies and, simultaneously released vapours of an odour . Avoidance of the odour associated with the shocks, later displayed by almost 95 per cent of the ,genetically 'normal' flies, was taken as an evidence of memory formation. Tully found that after 10 'training' sessions, the lesson was con- solidated into long-term memory.

Tully and his colleague Jerry Yin have zeroed in on the role played by a gene called the CREB. In fruitflies, this gene acts both as an :ctivator' and a 'repressor' protein. Researchers opine that fluctuation in the levels of these proteins in the nerve cells directly influence the conversion of short-term 'reflex action' memory into the long-term variety. When CREB is found in excess as the activator variety over the repressor one. long-term memory forms.

Tully and Yin 'rigged' a CREB ~imula- tor to act as the repressor type. When the repressor was turned on by warming a test-tube filled with flies, most of the flies failed the long-termmemory test in the electroshock therapy. Moreover, when the activator CREB simulator was triggered. the flies formed long-term memory in just one training session instead of the usual 10.

CREB gene simulation studies have shown promising results in experiments on mice and iea-slugsas well. Tully, therefore, assumes that the mechani$m by which CREB regulates memory is con- served and sharpened by evolution from the lower forms of life to way uR the lad- der -humans. His observations have shown that increasing the level of stim- uli gives rise to an excess of repressor CREB. which try to inhibit long-term memory formation to save the brain from memory overload. In tests inter- spersed with periods of rest, however, the activator overpowers the repressor, and some of the short-term memory gets converted into itslong2term variety. This is an exact analogy of how students who try to cram too much on the eve of an examination end up forgetting most in the long run.

Further researches have also showed how the brain processes different stimuli. The part of the brain responsible for fear, for example, has always an excess of activator CREB. A long-term memory vital for survival can be stored after a single lesson. A burnt child fears the fire, for instance.

Focussing on his theory that the essential mechanism of memory lies in a cellular process common to all nerve cells in all species, Tully is hopeful that his research one day can lead to memory- enhancing drugs. A drug which stimulates the CREB activator can bolster long-term memory and reinforce the remaining healthy brain cells of an Alzheimer's patient. cREB repressors can be administered to trauma victims to minimise mentally disabling memories. Oncogene Science Limited, a biotechnology company of Long Island, New York, has already started discussions with Tully's laboratory for a memory-research partnership, which might eventually involve a major pharmaceutical company.

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