Solving the mystery of sleep
~Developing new intervention methods for healthy slumber~
The familiar phenomenon of sleep is, in fact, a great mystery in neuroscience; for example, we still do not fully understand why we have to sleep or how daily sleep amounts are kept relatively constant. Although our discovery of orexin has helped to unlock the door to the sleep disorder narcolepsy, the black box of sleep/wake control still remains a challenge for scientists. In order to crack open the black box, Yanagisawa/Funato Laboratory is engaged in a highly ambitious project aiming at forward genetic analysis of randomly mutagenized mice for sleep abnormalities. We have so far screened over 7,000 mice and identified a dozen pedigrees with heritable sleep abnormalities. Already, three or more causative gene mutations have been successfully identified. We expect that functional analyses of these genes will reveal a central pathway for the regulation of sleep. Using a combination of genetically modified mice and gene delivery through viral vectors, we are working on identifying the neural circuits responsible for sleep regulation through visualization and manipulation of specific cells. Patch-clamp electrophysiology in brain slices is used in combination with simultaneous multicellular recording and imaging in naturally sleeping and waking mice. Our laboratory is also well equipped to perform biochemical and behavioral experiments. There are few laboratories around the world actively pursuing research based on such a wide range of experimental methods. In other words, we fully recognize that unlocking the mysteries surrounding sleep will require such a multi-pronged approach.
At Yanagisawa/Funato Laboratory, we are also focusing on basic research that leads to clinical applications. In particular, one approach we are actively pursuing is to develop small molecule agonists for the orexin receptor. These compounds will not only be indispensable chemical tools to manipulate sleep and wakefulness in experimental animals, but also become candidates of a novel drug for the mechanistic treatment of narcolepsy and other conditions with excessive sleepiness. In addition, our laboratory is exploring the relationship between sleep with exercise, nutrition, and metabolism. We hope that our research will provide a scientific basis to recommend a lifestyle that promotes healthy sleep.