March 16, 2016

expert reaction to retrieving memories in mice

A study published in the journal Nature has investigated mechanisms which control memory in mouse models of the disease.

Dr Mark Dallas, lecturer in cellular and molecular neuroscience at the University of Reading, said:

“This is an exciting study, and while it is unlikely to lead to new treatments for dementia patients any time soon, it should help scientists understand more about the memory loss symptoms associated with diseases such as Alzheimer’s.

“This builds on previous research showing that while people with Alzheimer’s still retain memories, their brains have problems accessing them.

“In a mouse model of Alzheimer’s the results illustrate the potential to reconnect nerve cells to retrieve previously learnt behaviours, although only in the short term.

“While this is a robust piece of science, it uses techniques that would be difficult to test on people. It does open up possibilities for scientists to ‘unlock’ brain connections to reveal memories, but it may be a step too far to translate this into human patients. Only time will tell.

“Our hope is that this will inform scientists as we look to understand why memory loss is one symptom of Alzheimer’s Disease, and provide better ways to manage it.”

Dr Simon Ridley, Director of Research at Alzheimer’s Research UK, said:

“This technically challenging study tells us more about the mechanisms underpinning memory and provides a useful starting point to understand how this process can go wrong in diseases like Alzheimer’s. The findings suggest that early memory problems in mice with features of Alzheimer’s could be driven by problems retrieving stored memories rather than laying down those memories in the first place. While the findings raise intriguing questions about whether it’s possible to recover lost memories, there is a long way to go to understand this process in people and how it’s affected over the course of a disease like Alzheimer’s. The mice in this study had not started to develop some of the other key features of Alzheimer’s, such as the build-up of toxic proteins, and these changes are also likely to impact on normal nerve cell function.

“Memory loss is a well-recognised symptom of Alzheimer’s, but the disease can also have profound effects on personality, behaviour, and communication. It’s important to understand more about the mechanisms driving these symptoms to better understand how to develop approaches to help those living with dementia. Research to address fundamental questions about the biology of the brain and how it’s affected in Alzheimer’s is crucial, and we must ensure this knowledge is translated into benefits for people with dementia and their families as quickly as possible.”

Dr Tara Spires-Jones, Reader and Chancellor’s Fellow, Centre for Cognitive and Neural Systems, University of Edinburgh, said:

“The impressive study published in Nature today by Nobel Prize winner Susumu Tonegawa and his team shows that in a mouse model of early Alzheimer’s disease, new memories can be made but they cannot be accessed long term. Remarkably, activating the brain cells involved in the formation of a memory allowed mice to retain the memory longer. These data highlight the importance of the synaptic connections between brain cells as crucial to the loss of memory in Alzheimer’s.

“These are elegant experiments that extend what we know about the formation and loss of memories in Alzheimer’s models. However, these results are not directly translatable to help people with dementia due to the invasive nature of the experiments. It is important to keep in mind that brain cells start dying very early in the disease process in people with Alzheimer’s, so even if we can harness these impressive results from disease models, they would have to be applied in humans long before dementia is diagnosed.”

Dr Doug Brown, Director of Research and Development, Alzheimer’s Society, said:

“One of the key issues with understanding memory loss in Alzheimer’s is that we don’t know whether people are having problems storing memories or recalling them. This study in mice helps us to unpick the underlying processes and problems that lead to memory loss in the earliest stages of Alzheimer’s disease – this new evidence suggests that memory recall is the issue.

“While interesting, the practicalities of this approach – using a special blue light to stimulate memory – means that we’re still many years away from knowing if it would be possible to restore lost memories in people.”

Prof. Richard Morris, Professor of Neuroscience, University of Edinburgh, said:

“When someone with early Alzheimer’s is forgetful, it is tempting to suppose that the memory is lost. However, echoing classic work by Elizabeth Warrington at the National Hospital in Queens Square London over 30 years ago, forgetfulness can also happen when the recall or retrieval mechanisms of the brain are compromised.

“This fine study using a genetic mouse model of Alzheimer’s disease (AD) coupled to optogenetics offers the tantalizing idea that ‘tagged’ memories can be reactivated by light. The fascinating technique developed by the Nobel Laureate Susumu Tonegawa and his team at MIT cannot be used in humans, but it indicates that forgetfulness in AD mice may also be an access problem.

“The issue of forgetfulness over time also has massive diagnostic implications. My own laboratory in Edinburgh has evidence (under review) that when animals are tested very early in the disease process, they learn and remember well, but the forgetfulness over time is already present long before any pathology in the brain. If this is also true of humans, it implies that forgetfulness over time – such as over several days – may be present in people who are at risk of AD or in the early pre-diagnostic phase.

“This really matters, as it raises the possibility that simple cognitive tests could be used to ‘screen’ for impending AD by testing forgetfulness at long intervals. Not for the first time, or surely the last, animal models of age-associated brain diseases are offering fresh insights into how to address this ‘grand challenge’ of our age.”

‘Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease’ by Roy et al. published in Nature at 18:00 UK time on Wednesday 16^th March. 

Declared interests

None declared