Hope for insomniacs as scientists uncover how the brain resists sleep

Scientists have identified a group of neurons that can help us stay awake when it matters.

They found a neural circuit in the brain that controls wakefulness and could offer new treatments for insomnia, oversleeping and sleep disturbances linked to depression.

Insomnia, the difficulty of getting to sleep or staying asleep for long enough to feel refreshed the next morning, regularly affects around one in every three adults, particularly the elderly.

Scientists at the California Institute of Technology wanted to explore how people overcome tiredness in the face of a looming deadline or rouse themselves in the dead of night to feed a crying baby.

Assistant Professor Viviana Gradinaru said: "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.

"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 researchers first looked at DRNDA neurons in mice and measured DRNDA activity while the animals encountered salient stimuli, such as the arrival of a potential mating partner, or a sudden unpleasant sensation, or food.

They found the DRNDA neurons were highly active during these events, which led the researchers to theorise that the neurons send signals of salience and arousal, which can then modulate the state of sleep or wakefulness.

Study first author Ryan Cho said: "We then measured DRNDA activity throughout the sleep/wake cycle and found that these neurons are least active when the animal is sleeping and increase in activity as the animal is waking up.

"We aimed to discover whether this was just a correlation or if the activity of the neurons was actually causing changes in sleep-wake states."

They used a technique called optogenetics to engineer DRNDA cells to be stimulated by light.

After stimulation during the time the animal would normally sleep, it was found the mouse woke up from sleep and remained awake.

The reverse was true when the activity of DRNDA was chemically silenced and found the animal was likely to fall asleep, even in the face of motivationally important stimuli, such as the odour of a predator or a mating partner.

The researchers said this implied that activity of the DRNDA neurons truly governed sleep-wake behaviours.

Finally, the researchers examined the role of these neurons in awaking due to external stimuli.

The neurons' activity was silenced with optogenetics, and a loud noise was played while the animals were asleep.

Whereas control mice often woke up, the mice with blocked DRNDA often ignored the sound and remained asleep.

Prof Gradinaru added: "These experiments showed us that DRNDA cells are necessary for full wakefulness in the face of important stimuli in mice.

"DRNDA neurons are found analogously in humans, and while they have not been studied in depth, their degeneration has been correlated with excessive daytime sleepiness in patients with neurodegenerative disorders such as multiple systems atrophy and Lewy body dementia.

"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 study was published in the journal Neuron.