Remember, remember

时间:2019-03-08 07:09:23166网络整理admin

By Nell Boyce RATS with amnesia have provided a new insight into the biochemical basis of forgetfulness. The finding may lead to drugs for treating memory loss associated with ageing, say researchers in the US. Researchers have known for decades that they can make rats forgetful by creating lesions in their fornix, a bundle of nerves in the brain connected to the hippocampus. When normal rats learn to avoid a dark chamber that gives them an electric shock through their feet, they remember for several days to choose the safe, bright chamber. But rats with lesions on their fornix only remember to avoid the dark chamber for a few hours, suggesting that they can form short-term memories but not long-term ones. No one knew how the fornix consolidated long-term memories, but a new experiment suggests a biochemical explanation. Cristina Alberini and her colleagues at Brown University in Providence, Rhode Island, decided to look at how fornix lesions affect the activation of a protein called CREB in the hippocampus during learning. CREB can exist in “active” or “inactive” forms, and previous studies in sea snails and fruit flies have suggested that active CREB is essential for the creation of long-term memories. In rats with no fornix lesions trained in the light and dark chambers, hippocampal levels of CREB activation soared to around 150 per cent of levels in control animals that had received no training. These levels remained high for as long as nine hours after training. Rats with fornix lesions, however, showed no increase in CREB activation compared with the controls (Nature Neuroscience, vol 2, p 309). “The importance of this finding is that for the first time, we now know that CREB-dependent response in the hippocampus is modulated via the fornix,” says Alberini. “This provides a possible molecular basis for amnesia associated with the fornix and related structures.” In November last year, Daniel Storm and his colleagues at the University of Washington in Seattle also showed that training rats activates CREB in their hippocampus as they lay down long-term memories. But while that study showed CREB activation in rats who could remember, this one shows that activation fails to occur in forgetful rats. “It’s the other side of the coin and it’s a good piece of work,” Storm says of Alberini’s latest research. “What is new is the disappearance of CREB with the amnesiac mode,” agrees Jerry Yin of Cold Spring Harbor Laboratory in New York. Four years ago, Yin and his colleague Tim Tully gave fruit flies the equivalent of a photographic memory by genetically engineering them to produce extra CREB. “There’s a lot of us that believe it’s a very good drug target site,” says Storm, who advises a company called Helicon Therapeutics, founded by Yin and Tully. The company hopes to develop drugs that treat memory disorders by boosting CREB activity. After screening around 200 000 drug candidates, it recently found one promising enough to test in simple animal models. “It looks very hopeful,