We’re Taking the First Steps Toward a Cure for Narcolepsy
The orexin neurons are a very big deal, and not just for those like me who’ve lost them. Present in every major class of vertebrate, they have to be doing something seriously important. When de Lecea first described the orexins in 1998, he was in his mid-20s and had only recently moved from Barcelona in Spain to San Diego. In 2006, he made the move from there to Stanford to be closer to the sleep action. “To be honest, I thought we’d understand the system much better at this point than we actually do,” he says.
But we have found out a lot, particularly thanks to optogenetics, a technique de Lecea helped pioneer. By deploying a virus, a promoter and a gene found in blue-green algae, it is possible to render a particular population of neurons sensitive to light.
To illustrate this wizardry, de Lecea brings up a video on his laptop. There is a mouse in a cage that has been engineered so its orexin neurons will fire in response to light. There is a thin fibre-optic cable running into its brain. “The mouse is asleep,” he says, waves of electrical activity characteristic of deep sleep spooling across an inset video at the top of the screen. The optic cable comes alive, a pulse of bluish light flashing for precisely ten seconds. The light-sensitive orexin neurons release their neuropeptides and, all of a sudden, the mouse wakes up. When the light goes off, it falls asleep as rapidly as it awoke.
There can be few more striking illustrations of the power of the orexins than this. Completely unexpectedly, I feel my tear ducts tingling and, for a split-second I almost envy the mouse.
Using optogenetics and other methods, de Lecea has been able to show that the orexins have a powerful effect on many important neurological networks. In some settings, they act like neurotransmitters, crossing gaps in neurons to activate target neurons that release a chemical called norepinephrine throughout the brain’s cortex.
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