Mind That Alarm Clock

By Steve Mitchell
ScienceNOW Daily News
17 October 2007

A new study has identified brain cells that play a key role in ensuring that we rise and shine when the alarm clock buzzes. The findings could lead to a better understanding of sleep disorders.

People with narcolepsy--a condition marked by falling asleep at inappropriate times--have fewer neurons that produce a small protein called hypocretin, also known as orexin (ScienceNOW, 29 January). So scientists had a hunch that these neurons, which are located in the hypothalamus region of the brain, play a role in transitioning from sleep to wake states, but their exact function had been difficult to pin down. Now, a team led by neuroscientist Luis de Lecea of Stanford University in Palo Alto, California, has literally shed some light on the problem.

The researchers used a virus to insert the gene that encodes a light-sensing protein into hypocretin-producing neurons in the brains of mice. This enabled them to activate the neurons by shining a laser deep into the brain via fiber optics. When the cells were activated, sleeping mice woke faster than animals that did not have their neurons stimulated, the researchers report online today in Nature.

Further experiments indicated that hypocretin is key in stimulating the transition from asleep to awake. Mice given a compound that blocks the action of hypocretin, for example, woke up more slowly upon activation of the neurons than did mice given a placebo. Knockout mice that lacked the gene for hypocretin also had a delay in waking up, although they still awoke faster than normal mice that did not have their neurons stimulated, suggesting that additional chemicals are involved in the process. "The hypocretin-producing neurons are very important in switching from sleep to wakefulness," de Lecea says, noting that the findings help explain the sleep disorders in narcoleptics who are deficient in these types of cells.

"It's a major breakthrough," says Barbara Jones, a neuroscientist at McGill University in Montreal, Canada. Priyattam "Peter" Shiromani, a neuroscientist at Harvard Medical School in Boston, Massachusetts, adds that the study "has huge implications for insomnia, where for the first time one can dampen these neurons and promote sleep." And neuroscientist Meenakshi Alreja of Yale University says the study "opens the door for many new investigations" into other processes known to be modulated by hypocretin neurons, including heart rate, feeding, and drug-seeking behavior.