Fluorescent light micrograph of neuronal (nerve cell) fibres in bright red and green.

Artificially coloured nerve fibres in a mouse’s hippocampus, the brain region where new memories are encoded.Credit: Mark & Mary Stevens Neuroimaging & Informatics Institute/Science Photo Library

New clues have emerged in the mystery of how the brain avoids ‘catastrophic forgetting’ — the distortion and overwriting of previously established memories when new ones are created.

A research team has found that, at least in mice, the brain processes new and old memories in separate phases of sleep, which might prevent mixing between the two. Assuming that the finding is confirmed in other animals, “I put all my money that this segregation will also occur in humans”, says György Buzsáki, a systems neuroscientist at New York University in New York City. That’s because memory is an evolutionarily ancient system, says Buzsáki, who was not part of the research team but once supervised the work of some of its members.

The work was published on Wednesday in Nature1.

Window on the brain

Scientists have long known that, during sleep, the brain ‘replays’ recent experiences: the same neurons that were involved in an experience fire in the same order. This mechanism helps to solidify the experience as a memory and prepare it for long-term storage.

To study brain function during sleep, the research team exploited a quirk of mice: their eyes are partially open during some stages of slumber. The team monitored one eye in each mouse as it slept. During a deep phase of sleep, the researchers observed the pupils shrink and then return to their original, larger size repeatedly, with each cycle lasting roughly one minute. Neuron recordings showed that most of the brain’s replay of experiences took place when the animals’ pupils were small.

That led the scientists to wonder whether pupil size and memory processing are linked. To find out, they enlisted a technique called optogenetics, which uses light to either trigger or suppress the electrical activity of genetically engineered neurons in the brain. First, they trained engineered mice to find a sweet treat hidden on a platform. Immediately after these lessons, as the mice slept, the authors used optogenetics to reduce bursts of neuronal firing that have been linked to replay. They did so during both the small-pupil and large-pupil stages of sleep.

Once awakened, the mice had completely forgotten the location of the treat — but only if firing had been reduced during the small-pupil stage. “We wiped out the memory,” says Wenbo Tang, a co-author of the Nature paper and a systems neuroscientist at Cornell University in Ithaca, New York.

By contrast, when the team reduced bursts of neuronal firing during the large-pupil phase shortly after a lesson, the mice went straight to the treat — making clear that their fresh memories were intact.

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