It's happened to all of us at some point: a loud noise in the middle of the night wakes you up in a panic. Even if it turns out to be just a neighbor slamming their door, your brain is wired to react like the world is coming to an end, just in case it's something you need to deal with. But how exactly does the brain overcome the powerful urge to sleep? Caltech researchers may have identified the neural circuit responsible in mice, and their findings could help treat people with various sleep disorders.

Many of the workings of the human brain remain a riddle, and sleep is one of the more mysterious things it does. Over the last few years, studies have found a "hot zone" that appears to be the dream center of the brain, investigated how sleep affects the synapses between neurons, and altered conscious states by stimulating the thalamus. The Caltech team wanted to study how salient stimuli – important events like loud noises or the smell of a predator – rouse the brain from sleep.


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"To answer this question, we decided to examine a region of the brain, called the dorsal raphe nucleus, where there are an under-studied group of dopamine neurons called dorsal raphe nucleus neurons, or DRNDA neurons," says Viviana Gradinaru, lead researcher on the study. "People who have damage in this part of their brain have been shown to experience excessive daytime sleepiness, but there was not a good understanding of the exact role of these neurons in the sleep/wake cycle and whether they react to internal or external stimuli to influence arousal."

The first step for the team was to study how the DRNDA neurons function in mice during normal wakefulness, and found that they were particularly active when the animal was exposed to salient stimuli, like food or a potential mate. But correlation doesn't equal causation, so the researchers then set out to see if stimulating these neurons would trigger changes in alertness.

To do so, mice were bred with DRNDA cells that would respond to light, in a process called optogenetics. Sure enough, when these neurons were stimulated while the mouse was asleep, it woke up and stayed awake. By the same token, when DRNDA was chemically silenced the animals would tend to fall asleep even when presented with the odor of a predator or partner, which would normally keep it up.

In the third experiment, the team silenced DRNDA through optogenetics, and played a loud noise to these mice while they slept. The noise was enough to wake control mice, but those with blocked DRNDA snoozed right on through. In future, the team plans to study if this region of the brain affects humans in the same way, and if so, how that might lead to new treatments for sleep disorders.

"These experiments showed us that DRNDA cells are necessary for full wakefulness in the face of important stimuli in mice," says Gradinaru. "Further work is necessary to establish causation in humans and to test the potential of the DRNDA as a therapeutic target for insomnia or oversleeping, and for sleep disturbances that accompany other psychiatric disorders such as depression, bipolar disorder, and schizophrenia."

The research was published in the journal Neuron.

Source: Caltech