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How the brain overrides the urge to sleep in order to stay awake

Scientists at the California Institute of Technology have identified a neural circuit in the brain that allows humans to fight off sleep.

The findings could have implications for treating sleep disorders such as insomnia and oversleeping, the researchers said.

The team studied DRNDA neurons in mice, measuring DRNDA activity while the animals encountered stimuli, such as the arrival of a potential mating partner, or a sudden unpleasant sensation, or food. The DRNDA neurons were highly active during these events, which led the researchers to theorize that the neurons send signals of salience and arousal, which can then modulate the state of sleep or wakefulness.

“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,” says Ryan Cho, a Caltech graduate student and the first author on the paper. “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.”

The researchers used a technique called optogenetics to engineer DRNDA cells to be stimulated by light. After stimulating these neurons with light during the time that the animal would normally sleep, the research team found that the mouse woke up from sleep and remained awake.

The reverse was true when the activity of DRNDA was chemically silenced. The animal was likely to fall asleep, even in the face of motivationally important stimuli, such as the odor of a predator or a mating partner. This implied that activity of the DRNDA neurons truly governed sleep-wake behaviors.

Finally, the researchers examined the role of the neurons in awaking due to external stimuli. The neuron activity was silenced with optogenetics, and a loud noise was played while the animals were asleep. Mice with blocked DRNDA often ignored the sound and remained asleep.

“These experiments showed us that DRNDA cells are necessary for full wakefulness in the face of important stimuli in mice,” said Viviana Gradinaru, Caltech, Assistant Professor of Biology and Biological engineering. “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,” Gradinaru said.

The study is published in the online journal Neuron.

By: David Beasley, Staff Writer

Source: California Institute of Technology

Photo Credit: Gradinaru lab/Caltech

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