A hit of dopamine sends mice into dreamland

A quick surge of dopamine shifts mice into a dreamy stage of sleep.

In the rodents’ brains, the chemical messenger triggers rapid-eye-movement sleep, or REM, researchers report in the March 4 Science.

During a night’s sleep, people and other animals cycle between phases called non-REM sleep and REM, a sleep stage that usually comes with vivid dreams. But what causes those transitions is mysterious, says neurologist and sleep researcher Thomas Scammell of Harvard Medical School who wasn’t involved in the study. These new results are some of the first to show a trigger for the shifts, Scammell says. Understanding these transitions in more detail could ultimately point to ways to treat sleep disorders in people.  

Certain nerve cells residing in a part of the mouse brain called the ventral tegmental area can pump out dopamine, a molecule that has been linked to pleasure, movement and learning, among other things. These cells can deliver dopamine to the amygdalae, two almond-shaped structures deep in the brain that are closely tied to emotions.

Using a molecular sensor that can tell exactly when and where dopamine is released, neuroscientist Takeshi Sakurai from the University of Tsukuba in Japan and colleagues saw that dopamine levels rose in the amygdalae just before mice shifted from non-REM sleep to REM sleep.

Next, the researchers forced the mice into the REM phase by controlling those dopamine-producing nerve cells using lasers and genetic techniques — a method called optogenetics. Compelled with light, the nerve cells released dopamine in the amygdalae while mice were in non-REM sleep. The mice then shifted into REM sleep sooner than they typically did, after an average of about two minutes compared with about eight minutes for mice that weren’t prompted to release dopamine. Stimulating these cells every half hour increased the mice’s total amount of REM sleep.

Additional experiments suggest that these dopamine-making nerve cells may also be involved in aspects of narcolepsy. A sudden loss of muscle tone, called cataplexy, shares features with REM sleep and can accompany narcolepsy (SN: 10/9/10). Stimulating these dopamine-making nerve cells while mice were awake caused the mice to stop moving and fall directly into REM sleep.

The results help clarify a trigger for REM in mice; whether a similar thing happens in people isn’t known, Sakurai says. Earlier studies have found that nerve cells in people’s amygdalae are active during REM sleep, he says, hinting at a role for the brain structure.

Many questions remain. Drugs that change dopamine levels in people don’t seem to have big effects on REM sleep and cataplexy, Scammell says. But these drugs affect the whole brain, he points out, and it’s possible that they are just not selective enough. “My overall question about this is, ‘How can we translate this to humans?’” Scammell says.