How memories are made
A UK-led team of scientists has identified one of the key proteins involved in learning and forming memories. The findings, published in the Proceedings of the National Academy of Sciences (PNAS), have important implications for the study of Alzheimer's disease. The researchers were financed in part by a Marie Curie Excellence Grant from the EU's Sixth Framework Programme (FP6). Scientists have long sought to establish the exact mechanism by which our brains learn and form long-lasting memories. Memories are stored in a complex network of neurons. To do this, the neurons must activate a mechanism to form new proteins that strengthen the connections (synapses) between them. A group of proteins called G protein-coupled receptors (GPCRs) are known to play an important role in regulating learning and memory. A subtype of these GPCRs, called the 'muscarinic acetylcholine receptor family', is implicated in Alzheimer's disease. Recent studies have focused on the M1-muscarinic receptor, but results have been uncertain. In the current study, scientists focused on the M3-muscarinic receptor, a protein that is expressed widely in the central nervous system. They studied a kind of mouse whose M3-muscarinic receptor was phosphorylation-deficient (phosphorylation, the adding of phosphorus to a protein, can activate or deactivate that protein). The mice underwent fear conditioning, and their performance was compared with that of normal mice. After the trials, their brain tissue was analysed. The scientists found that both the M3 receptor and its phosphorylation status are essential for learning and memory. 'This protein is present in the part of the brain in which memories are stored,' explained Professor Andrew Tobin of the University of Leicester in the UK. 'We have found that in order for any memory to be laid down, this protein, called the M3-muscarinic receptor, has to be activated.' The group discovered that the M3-muscarinic receptor undergoes a very specific change during the formation of a memory. Indeed, without undergoing this change the memory will not be formed. 'In this regard, our study reveals at least one of the molecular mechanisms that are operating in the brain when we form a memory and as such this represents a major breakthrough in our understanding of how we lay down memories,' said Professor Tobin. The study sheds light on important questions about how the brain works, and as such will help researchers studying the causes of Alzheimer's disease. This progressive form of dementia destroys brain cells, causing severe memory loss and problems with thinking and behaviour. As yet, there is no cure. 'This finding is not only interesting in its own right but has important clinical implications,' said Professor Tobin. 'One of the major symptoms of Alzheimer's disease is memory loss. Our study identifies one of the key processes involved in memory and learning and we state in the paper that drugs designed to target the protein identified in our study would be of benefit in treating Alzheimer's disease.' Professor Tobin added: 'It has been fascinating to look at the molecular processes involved in memory formation. We were delighted not only with the scientific importance of our finding but also by the prospect that our work could have an impact on the design of drugs for the treatment of Alzheimer's disease.'
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United Kingdom, United States