Remote-controlled flies point to what memories are made of

15 October 2009

Scientists have used light to program the memories of fruit flies. The results of the Oxford University-led study are published in the journal Cell.

The research team, funded by the UK Medical Research Council, genetically engineered the fruit flies so that a small set of nerve cells in the brains would ‘fire’ in response to a flash of laser light. This showed which cells are involved in how a fruit fly learns and remembers what to avoid, and offers an exciting new opportunity to investigate how memories are formed.

‘Remote-controlling these cells and turning them on using light creates an illusion in the brain of the fly that it is experiencing something bad. The fly learns from the “mistake” it never really made and improves its actions the next time,’ explains Professor Gero Miesenböck of the Department of Physiology, Anatomy and Genetics at Oxford University, who led the work.

The Oxford scientists, with colleagues at the University of Virginia, Charlottesville, demonstrated that they could use flashes of laser light to train flies to dislike a certain odour.

‘We tracked the flies using a video camera as they moved around a small chamber while two different odours were fed into the chamber from either end. We found that we could implant a lasting preference for one odour over the other by remotely activating a specific set of brain cells each time a fly strayed into a particular odour,’ says Dr Adam Claridge-Chang, who is now at the Wellcome Trust Centre for Human Genetics at Oxford University.

Using this method, the researchers were able to pinpoint the precise nerve cells that are responsible for telling the flies that they’ve done wrong, narrowing down the search from the 100,000 cells in the brain of a fruit fly to a set of just 12 neurons.

‘Surprisingly, the source of these signals is in a limited number of cells – just twelve,’ says Professor Miesenböck. ‘These cells send the signals that train the fly to associate the odour with something bad, so wherever their signals go must be the seat of memory. We can now follow this up and start to characterise the process by which memories are formed and organised.’

‘There’s hope that one can also find the cells that lie upstream of these 12 neurons and calculate some prediction of impending reward or punishment’, says Dr Claridge-Chang. Professor Miesenböck’s group is aiming to uncover the algorithm used to make this calculation, and to find out whether it resembles the temporal difference algorithm developed by researchers working on machine learning more than 20 years ago.

While this work has been done in fruit flies, general lessons about how actions are learned and memories are stored should hold true for humans.

‘Biology teaches us that fundamental mechanisms tend to be conserved. Learning about the storage of memories from brain cells in flies should tell us a lot about how they are stored in humans,’ says Professor Miesenböck.

Professor Miesenböck has pioneered this method of genetic engineering to remote control the action of specific cells within tissues, or whole organisms like worms, fruit flies, fish and mice, using light from the outside. These efforts have given rise to a new field sometimes called ‘optogenetics’, to indicate that sensitivity to light is encoded genetically. A separate paper by Professor Miesenböck summarising the status of this new field is to be published in Science the same day. As the ability to write memories directly to the brains of fruit flies demonstrates, optogenetic techniques have particular power in neuroscience.

‘The great advantage is that we are no longer just passive observers of processes in the brain. In the past, neuroscientists had to be content with recording the chatter of brain cells and trying to infer what it all meant. The ability to talk back and influence behaviour directly is proving quite valuable,’ says Professor Miesenböck.

For more information please contact Professor Gero Miesenböck on 01865 282261, 01865 282246 (PA) or gero.miesenboeck@dpag.ox.ac.uk
Or the Press Office, University of Oxford on +44 (0)1865 280530 or press.office@admin.ox.ac.uk