The seat of dreams

Researchers discover a new circuit controlling REM sleep in our brains

By Amy McDermott. Photographs by Christian Whiting. 

Yang Dan leans over a piece of scrap paper in her bright, high-ceilinged Berkeley office. She speaks slowly and smiles warmly as she scrawls dots and lines across the page.

Dan, a professor of neurobiology at UC Berkeley and a Howard Hughes Investigator, is drawing the neural circuitry of a mouse’s brain.

Her fingers trace the page as she explains her drawing — a pathway through the brain that can plunge sleeping mice into the depths of Rapid Eye Movement, or REM sleep. It's the kind of sleep associated with vivid, sensory dreams and skeletal muscle paralysis, she says. REM’s been implicated in learning, memory, and insight.

Dan’s research group discovered the pathway, and published it in the journal Nature Oct. 15. They found that a cluster of neurons at the base of the brainstem can change the activity of a mouse’s whole brain, sending it into REM.

Light Flips the REM Switch

To do their work, Dan and her colleagues used a technique that may seem like science fiction.

They used viruses to inject foreign DNA into mice brain cells, in a region of the brain stem called the medulla. That region had been implicated as important for REM in previous genetic studies, but the exact pathway remained unknown.

The DNA that the viruses injected was from light-sensitive algae. It embedded itself in the mouse’s own DNA, and was subsequently expressed as special pores on the outside of mouse neurons.

The pores open up in response to light, letting molecules flow in and out of the cell, and changing the voltage across its membrane. Since “everything in the nervous system is electrical,” Dan explained, changing the voltage activates the neuron, causing it to fire electrical impulses, or “spike.”

“Basically, in the nervous system the communication between different parts of the brain is all carried by the spiking,” Dan added. Neurons communicate through electrical signaling. When one spikes, she explains, it passes that electricity through the brain to another neuron downstream. That cell then fires in turn, propagating the signal.

To trigger the spiking, the scientists stuck an optic fiber deep into the brain, near the medulla. Hundreds of cells responded to the light, opening their pores and firing within milliseconds. Right on cue, the mice were plunged deep into REM sleep.

Stopping Other Cells

So how did that happen? The brain cells triggered REM by firing a signal down the spinal chord, and up into the higher reaches of the brain. This signal communicated with cells known to encourage non-REM sleep, and turned them off.

“The neurons we’ve activated, they’re inhibitory, ” Dan said. “So when they fire, they actually shut down the other neurons.“

The researchers think this is just one of many pathways controlled by brain cells in the medulla. Because they communicate with so many other places in the brain, the neurons might exert control in other, as yet undiscovered ways.

The Seat of Dreams

The cells that turn REM on probably don’t dictate how we experience it. The content of our vivid dreams, Dan says, is likely not controlled by these particular cells.

“My guess is that these neurons actually don’t directly encode what you dream,” she said. All they’re doing “is to sort of decide whether your whole brain is in the non-REM or REM state, or awake state. So that’s the decision.”She will continue to study this circuit in future, and hopes to find pathways that can trigger non-REM sleep too.

The next step is figuring out how this circuit interacts with previously-known REM sleep control areas, mostly in the brainstem, said Christa Van Dort, a researcher in the department of Brain and Cognitive Sciences at the Massachusetts Institute of Technology and instructor at Harvard Medical School, who was not involved in the study. The networks that regulate sleep in the brain “are more nuanced than we previously thought,” and may interact hierarchically, she explained. “This area had not previously really been included in sleep regulation but now based on their study it seems to have a pretty important role in REM sleep.”

While this study doesn’t tell us why we experience REM, it does help us understand how the brain controls sleep, Dan says. And in the long run, uncovering those mechanisms could help scientists figure out why we sleep at all.