Study reveals role of parvalbumin neurons in deep rebound sleep after sleep deprivation

Japan Science and Technology Agency (JST)Aug 13 2024

Professor Hiroki R. Ueda (RIKEN Center for Functional Biology, concurrently team lead), Dr. Kazuhiro Kon (at the time of the research, currently a postdoctoral fellow at Johns Hopkins University) and their colleagues at Graduate School of Medicine, The University of Tokyo, have elucidated the importance of proper regulation of the activity of parvalbumin (PV)-expressing neurons, the major inhibitory neurons in the cerebral cortex, in the long, deep sleep (rebound sleep) that occurs after prolonged wakefulness.

We have all experienced at one time or another that when we are sleep deprived, such as when we pull an all-nighter, we feel a strong sense of sleepiness, and our subsequent sleep is longer and deeper than usual. This indicates that the brain has a mechanism (sleep homeostasis) that records the history of wakefulness and compensates for the sleep needed based on that history. However, the mechanism of sleep homeostasis in the brain is not well understood.

By experimentally depriving mice of sleep, this research group showed that PV-expressing neurons in the cerebral cortex are activated when sleepiness increases and rebound sleep occurs. Furthermore, they elucidated that the activation of calcium/calmodulin-dependent kinase II (CaMKII), a protein phosphorylation enzyme, causes rebound sleep by activating PV-expressing neurons in response to sleepiness.

This study reveals a part of the molecular and neural mechanisms of sleep homeostasis, one of the major mysteries of sleep science. These results are expected to lead to the development of methods to appropriately control sleepiness while quantitatively monitoring it.

This result was obtained from JST Strategic Basic Research Programs ERATO: Research Project "UEDA Biological Timing." The project aims to elucidate the biological timing mechanisms underlying sleep-wake cycles by applying state-of-the-art technology in mouse genetics and human sleep measurement techniques.