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Scientists discover new role of "wake-up" neurotransmitter

Armen Hareyan's picture

Your brain tells you to wake up when it's light, which is why many night shift workers rely on window blinds or sleep masks to catch some Z's. You probably don't think twice about waking up in the morning, but when things go wrong with your brain's sleep-wake system, the results can be debilitating.

Professor of Psychiatry Jerome Siegel and his colleagues at UCLA's Semel Institute for Neuroscience and Human Behavior have discovered breakthrough information about the neurotransmitter hypocretin, a key piece to the puzzle of how your brain's sleep-wake system works. Their study in the October 26, 2011 issue of The Journal of Neuroscience (PDF) provides a better understanding of hypocretin that could lead to improved treatments for people with narcolepsy, Parkinson's disease and depression.

Scientists have known for years that, if your brain does not have enough hypocretin, you will feel sleepy. Anyone who suffers from narcolepsy understands just how devastating a lack of hypocretin can be. But the hypocretin system is only one of your brain's many arousal systems, which depend on a complex brew of neurotransmitters. Until now, scientists have supposed that your brain's different arousal systems overlapped each other, and that hypocretin created a general arousal of your brain.

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Siegel and his colleagues, however, found out that a lack of hypocretin does a lot more than make you sleepy. In their 2011 study, they compared normal mice with "knock-out" mice that lacked the gene for producing hypocretin cells in the brain's hypothalamus. The researchers taught the mice to press a lever to receive food or water, and tested them at these tasks both in a light environment and a dark one.

Surprisingly, while the knock-out mice's performance suffered dramatically in the light, the effect of reduced hypocretin disappeared when the mice performed the same task in the dark. Likewise, the hypocretin cells in the normal mice's brains were active only while they pressed the lever in the light, even though the hungry mice's brains were just as aroused by the food reward in the dark.

Another big surprise was that the hypocretin cells stayed quiet when the mice experienced negative arousal -- a shock to the foot in this case -- even though an EEG showed that their brains were in a high state of arousal. Also, the knock-out mice were just as good at working to avoid the foot shock as their normal counterparts.

This fits with the results of a 2000 study (PDF) in the journal Cognition and Emotion in which people with major depression worked harder on a memory task to avoid a penalty, but not to receive a reward. Non-depressed participants, however, worked harder both to avoid a penalty and to receive a reward. According to Siegel and colleagues, this effect may be linked to a problem with hypocretin in depressed individuals.

Hypocretin is not just about sleepiness; it's a part of your brain's response to light and of your ability to motivate yourself. Siegel and his colleagues believe that further research into hypocretin may lead to the development of new antidepressant medications and a better understanding of depression and motivation in narcoleptics and other people with hypocretin problems, such as Parkinson's disease patients.