Professor William Wisden,
Chair in Molecular Neuroscience
Department of Life sciences
Wolfson Laboratories, Imperial College, South Kensington London
Medical Research: What is the background for this study? What are the main findings?
Profs. Franks and Wisden: We were interested in finding out how a particular type of sedative drug, dexmedetomidine, works in the brain. This drug is increasingly used during intensive care for sedation of patients, but unlike other powerful sedatives, it induces a state whereby the patient can be temporarily woken up. This is a highly useful property because it means patients can be both sedated and responsive during procedures. The drugged sedative state induced by dexmedetomidine struck us as being highly similar to the deep sleep that we all need to have if we have been extensively sleep deprived. If people and animals are kept awake for extended periods of time, they have to sleep. Most people know this from common experience – catching up on lost sleep. But how and why we need to sleep after sleep deprivation is not known. We found that dexmedetomidine-induced sedation and this recovery sleep used the same brain circuits, in a tiny area at the base of the brain called the preoptic hypothalamus. To do this we used a new genetic technique in mice that allowed us to mark or “tag” which neurons in the mouse’s brain were active during sedation or recovery sleep after sleep deprivation. The beauty of this technique is that we could then specifically reactivate these same neurons several days later with a special molecule that only binds to the tagged neurons. This reactivation caused the mice to go into a deep sleep. We concluded that the sedative drug dexmedetomidine copies or hijacks the mechanism used by the brain to respond to sleep deprivation and trigger deep sleep.