Cambridge research delves into memory

By Ruth Beran
Monday, 28 November, 2005


Animals as diverse as sea slugs, fruit flies, mice and humans can learn. But how memories are stored in the brain and then retrieved is still a mystery, and Australian researcher Prof Seth Grant is trying to solve it.

Grant, who is head of the £6 million Genes to Cognition (G2C) program at Wellcome Trust's Sanger Institute in Cambridge, spoke at Melbourne's Mental Health Research Institute on Friday about insights being made into the mechanisms of cognition from research into genetics and proteomics.

Grant and his team are investigating synaptic plasticity -- the variability in the strength of signals transmitted through the synapses between nerves. "The enhancement of synaptic strength is a way of laying down a memory trace," said Grant. "An enhancement of learning would occur with an enhancement of synaptic strength."

The neurotransmitter N-methyl D-aspartate (NMDA) receptor -- which sits at synapses in the central nervous system -- is known to be crucial to the process of synaptic plasticity. Grant and others have found additional molecules involved in synaptic plasticity. For example, mice lacking a protein called PSD-95, which binds to the NMDA receptor, have severe learning deficits.

Grant believes the key to understanding the brain and its memories lies in looking at how proteins in the brain 'talk' to each other. Most research to date has studied individual proteins, which Seth said is akin to "studying the works of Shakespeare by looking only at a couple of sonnets."

In 2000, Grant's team found that the NMDA receptor is associated not only with PSD-95 but at least 100 proteins appear to function together as a large machine, translating the electrical information of nerve impulses into changes in the cell that store the information.

Grant has dubbed this complex the "hebbosome" in honour of Donald Hebb, who first mooted the existence of such a mechanism in 1949.

"We're trying to understand the importance of the genes that encode these components," said Grant. "We're interested in discovering fundamental principles that underlie the design of the complex. What is the biological program that is being built and constructed in the first place? How do all the parts fit together?"

Better understanding of the genes involved in learning and cognition could have implications for areas such as neuropsychiatric disorders, pain, addition, and improve diagnostics and treatments for disease, said Grant.

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