Using new technology to disrupt continuity of sleep in mice without changing other variables, scientists have concluded that interrupted sleep impairs memory. Writing in the 25 July 2011 early issue of the Proceedings of the National Academy of Sciences, researchers from the Universtiy of Stanford in the US describe how they used optogenetics to target specific neurons and found that a minimum amount of continuous sleep is crucial for memory consolidation.

People with certain neurological and psychiatric conditions that affect sleep continuity without affecting total sleep or sleep quality, often have memory problems. These conditions include sleep apnea, where the person stops breathing and can experience hundreds of "micro-arousals" a night, and alcoholism.

Although scientists have suspected for a while that sleep continuity is important for memory, it has not been easy to investigate, because the technology that allows manipulation of continuity of sleep without affecting other variables like quality and overall duration, has not been available until recently.

Even when you try to rouse a laboratory rodent using "gentle handling", it can raise stress levels, making it impossible to measure whether the outcome is due to sleep interruption or raised stress.

Co-leader of the study, Dr Luis de Lecea, an associate professor of psychiatry and behavioral sciences, who is currently investigating the neural circuitry underlying wakefulness, explained to the press:

"Rodents are very sensitive to physical awakenings. If you wake an animal up it's going to be up for awhile, and it will experience stress."

So the challenge was to come up with a technology that arouses key brain circuits for very short periods during sleep without affecting intensity and duration and causing stress.

Optogenetics uses light to control cells that have been genetically engineered to respond to light pulses. It is a new interdisciplinary field that combines optics and genetics to manipulate single events in specific cells in living tissue using millisecond timing to operate within similar timescales as target biological processes.

De Lecea describes the method as "a very fine, very subtle way of sleep fragmentation".

He and his colleagues write in their paper:

"We optogenetically targeted hypocretin/orexin neurons, which play a key role in arousal processes. We used optogenetics to activate these neurons at different intervals in behaving mice and were able to fragment sleep without affecting its overall amount or intensity."

Hypocretin/orexin neurons are important for switching brain circuits between sleep and wake states.

After undergoing sleep manipulation, the treated mice completed a task where they encountered two objects. One object was new to them and the other was one they had met before. Rodents spend more time with a new object than one they have already encountered.

The treated mice took as long to explore the "familiar" object as the new object, showing their memory had been affected. Control mice that did not undergo sleep manipulation, however, spent more time exploring the new object.

After experimenting with various amounts of sleep interruption, the researchers concluded that "memory was unaffected if the average duration of sleep episodes was maintained at 62 - 73% of normal".

Dr H. Craig Heller, study co-leader and professor of biology at Stanford, said the findings "point to a specific characteristic of sleep -- continuity -- as being critical for memory".

Although the authors did not establish how much uninterrupted sleep humans need to avoid memory impairment, they did suggest that memory problems in people who experience apnea and other sleep disorders are probably linked to disruption in continuity of sleep that these conditions cause.

Dr Asya Rolls, first author and postdoctoral scholar at Stanford, said this study is "just the first step in looking at one aspect of sleep". With her colleagues she now plans to study other sleep mechanisms that affect memory.

The researchers expect more studies will soon be using optogenetics to investigate sleep. At present the method can't be used on humans because it relies on genetic engineering to create the target cells.

Funds from the National Institute of Mental Health, Klarman Family Foundation, and Stanford's Department of Psychiatry and Behavioral Sciences helped pay for the study.

"Optogenetic disruption of sleep continuity impairs memory consolidation."
Asya Rolls, Damien Colas, Antoine Adamantidis, Matt Carter, Tope Lanre-Amos, H. Craig Heller, and Luis de Lecea.
PNAS, Published online before print July 25, 2011, doi: 10.1073/pnas.1015633108
Link to Abstract.

Additional sources: Stanford School of Medicine, Optogenetics Resource Center.

Written by: Catharine Paddock, PhD