Researchers have identified specific groups of neurons in the mouse brain that are activated after the rodents have been awake for a long time, driving them to get some sleep. If a similar system exists in humans, it could be targeted to help improve treatments for some sleep disorders. Inside the brain, several neural circuits regulate sleep and wakefulness, including neurons in the hypothalamus that act like a switchboard to control the process.
One or more of these circuits might be involved in why it is that the longer we are awake, the more irresistible the urge to close our eye becomes. But what actually drives this urge has long been a mystery. How wakeful rest may boost brain power in a manner similar to sleep To find out, Will Joo at the University of Basel in Switzerland and his colleagues have compared brain activation patterns in mice during normal sleep-wake cycles, sleep deprivation and in recovery sleep.
They did this by tracing how much protein is produced in cells by a gene called Fos, which is turned on when neurons get activated. This allowed them to identify brain areas in which activity correlated with time spent awake. Within one of these regions, the median raphe, they found two distinct neuronal populations that were increasingly activated the longer the animals stayed awake and which got quieter again after sleep started.
These populations are the GABAergic and serotonergic neurons, so named because the chemical messenger molecules they respond to are gamma-aminobutyric acid (GABA) and serotonin, respectively. The whole-brain Fos mapping is a real tour de force,” says Chiara Cirelli at the University of Wisconsin–Madison. To see whether these neuronal populations become more active simply because the mice had been awake for a long time or whether they do something more, Joo and his colleagues next used viruses to deliver a genetic package to the neurons to either activate or inhibit their action.
When both sets of neurons were artificially activated, the mice slept for twice or three times as long as control mice and spent more time in non-REM slow-wave sleep – in a way that resembles the deeper, recovery sleep humans have after we’ve been up for a long time. And when the neurons were inhibited, the mice slept about 70 per cent less than control mice – spending about 6.5 extra hours awake a day – without showing more of the anxiety-like behaviours that usually come with sleep deprivation for mice. However, the lack of sleep was lethal in about 17 per cent of the mice.
Your running style changes when you’re short of sleep The strong effect of activating and inhibiting the neurons means they don’t just signal that an animal has been awake, says team member Alex Schier, also at the University of Basel. It isn’t known if the same sleep-driving neuron populations exist in humans, but if they do, the findings could open doors to new therapies for some sleep-related conditions – once we know how the cells are communicating with other brain regions, say the researchers. Humans sleep the least of all apes – is it the secret to our success?
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