Optogenetics Used to Induce REM Sleep in Mice

Optogenetic activation of certain brain cells could be used to induce rapid-eye-movement (REM) sleep, which is crucial for keeping both body and mind healthy.

MIT researchers targeted cholinergic neurons in two parts of the mouse brainstem, finding that activating them during non-REM sleep increased the number of REM sleep episodes — but not REM sleep duration.

Triggering REM in mice involved inserting genetically modified, light-sensitive proteins into mice brain cells. These sensitized neurons were activated via a head-mounted fiber optic device.

The study, described in the Proceedings of the National Academy of Sciences (doi: 10.1073/pnas.1423136112), helps to clarify the mechanism by which REM sleep is controlled, and is a step toward understanding how to design natural sleep in humans, said postdoctoral researcher Christa Van Dort.

Confocal images show expression of the neurotransmitter acetylcholine (red), and the light-sensitive ion channel channelrhodopsin (green). The merged images at far right show neurons expressing both acetylcholine and channelrhodopsin (yellow). The top row displays the entire brainstem; the bottom row shows expression at the cellular level. Courtesy of the Brown Group/MIT.

“Figuring out how each of the components of sleep is controlled can help us design a way of reproducing natural sleep with different drugs in the future,” she said.

Natural sleep comprises alternating 90-minute periods of non-REM and REM sleep. Existing drugs used by insomniacs actually repress both REM and the deeper stages of non-REM sleep.

“What they do is create sedation,” said professor Dr. Emery Brown. “If you are lucky, the sedation allows your natural sleep mechanisms to take over.”

The different stages of natural sleep provide different benefits, Brown said. Studies in rodents have shown that learning occurs during REM sleep, for example, while slow-wave sleep, also known as non-REM stage three, is most important for feeling rested and refreshed.

Triggering more episodes of REM sleep alone could be used to enhance people’s learning and memory, Brown said.

“The long-term goal is to really understand what controls each phase of non-REM and REM sleep, and then to selectively induce them both, and reproduce the normal cycling of sleep stages,” Van Dort said.

For more information, visit www.mit.edu.