Research: Learning about brains

Cross-disciplinary approaches are shedding light on the molecular mechanisms of learning and memory.

The Genes to Cognition programme, an international collaboration led by Professor Seth Grant at the Wellcome Trust Sanger Institute, is dissecting the biological mechanisms of brain function at all levels, from genes to behaviour. Two papers highlight recent progress.

Fragile X syndrome, the most common cause of human X-linked mental retardation, is caused by alterations in the FMR1 gene. Working with colleagues in Rome, Professor Grant has found that the FMR1 protein has an unsuspected function: stabilising mRNA encoding PSD-95, a protein found at the synapse that is known to be involved in learning and memory. In mice lacking FMR1, PSD-95 mRNA disappeared rapidly, particularly in the hippocampus, a brain region crucial to the formation of new memories.

A second study looked at mice lacking the SAP102 gene, mutations in which cause learning difficulties in people. SAP102 mutant mice struggled to master tasks based on memorising spatial information, because they adopted a less efficient strategy than normal mice. Interestingly, though, in a separate test, the SAP102 mutant animals were actually quicker – they used a better strategy than the 'normal' one.

The SAP102 mutation was found to affect cell signalling through the ERK2 pathway, part of the biochemical system that creates cellular 'memory' by strengthening connections between neurons. In mice, this excessive activity could be blocked by drugs specific for ERK2.

The work hints at how conditions such as autism, where individuals may have learning deficits but also unusual skills, may be operating. It also raises the possibility that drug treatments might ultimately be able to reverse the symptoms of genetically linked neural developmental abnormalities.

External links

• Genes to Cognition
• Zalfa F et al. A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability. Nat Neurosci 2007;10(5):578–87.
• Cuthbert PC et al. Synapse-associated protein 102/dlgh3 couples the NMDA receptor to specific plasticity pathways and learning strategies. J Neurosci 2007;27(10):2673–82.