Wakefulness Cells


Certain groups of neurons determine whether light keeps us awake or not, says a new study.

Just a typical day for a hypocretin-deficient mouse. Okay, I'll wait for you to finish making that squinchy "Awww!" face, and then we'll move on with the article.

In the hypothalamus – a brain structure responsible for regulating hormone levels – specific kinds of neurons release a hormone called hypocretin (also known as hcrt or orexin). Hypocretin lets light-sensitive cells in other parts of the brain – such as the visual pathway – know that they should respond to incoming light by passing along signals for us to stay awake.

Scientists have understood for centuries that most animals and plants go through regular cycles of wakefulness and sleep – they call these patterns circadian rhythms or circadian cycles. More recently, researchers have begun unraveling the various chemical messaging systems our bodies use to time and control these cycles – enzymes like PER and JARID1a, which help give us an intuitive sense of how long we’ve been awake or asleep.

But now, as the Journal of Neuroscience reports, a team led by UCLA’s Jerome Siegel has isolated a neurochemical messaging system that dictates whether or not we can stay awake during the day at all. The team bred a special strain of mice whose brains were unable to produce hypocretin, and found that these mice acted like students in first-period algebra – even under bright lights, they just kept dozing off. However, they did jump awake when they received a mild electric shock:

This is the first demonstration of such specificity of arousal system function and has implications for understanding the motivational and circadian consequences of arousal system dysfunction.

What’s even more interesting, though, is that there’s a second half to this story – the dozy mice were perfectly perky in the dark:

We found that Hcrt knock-out mice were unable to work for food or water reward during the light phase. However, they were unimpaired relative to wild-type (WT) mice when working for reward during the dark phase or when working to avoid shock in the light or dark phase.

In other words, the mice without hypocretin stayed awake and worked for food just fine when the lights were out. So they probably have promising futures as bartenders or bouncers.

The takeaway here is that hypocretin isn’t so much responsible for enabling knee-jerk reactions as it is for helping mice (and us) stay alert and motivated to complete reward-based tasks when the lights are on. Without this hormone, we might act normally at night, but we just wouldn’t feel like staying awake when the sun was out.

And that’s exactly what Siegel’s team had found in several of their earlier studies, which linked human hypocretin deficiency with narcolepsy – a disease that causes excessive sleepiness and frequent daytime “sleep attacks.” These new results suggest that narcoleptic patients might have more success getting work done during the night, when their symptoms might be less severe.

Siegel also thinks clinically administered hypocretin might help block many effects of depression, and allow depressed patients to feel more motivated to get up and about during the day. If so, this could be a promising new form of treatment for that disease as well.

Finally, and perhaps most intriguingly of all, it’s likely that similar hormonal response “gateways” play crucial roles in other neurochemical arousal systems – like those involved in fearanger, and sexual excitement. If so, discoveries along those lines could provide us with some staggering new insights into the ways our brains regulate their own behavior.

So, I know what you’re probably wondering: am I really advocating the use of electric shocks to keep bored math students awake? Of course not – I think releasing wild badgers into the classroom would be much more effective.

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