Sleep Regulation Breakthrough: Enzymes That Control Your Wakefulness

In a **significant advancement** in sleep research, scientists from the Graduate School of Medicine at the **University of Tokyo** have discovered how specific proteins and enzymes regulate sleep and wakefulness. **Phosphorylation**, a chemical modification of proteins in neurons, plays a dynamic role in this regulation. The study focuses on **protein kinase A (PKA)** and dephosphorylation enzymes like **protein phosphatase 1 (PP1)** and **calcineurin**. PKA promotes wakefulness, while PP1 and calcineurin foster sleep. The team experimented with gene knockout mice and used viral vectors to modify enzyme expression. They found that activating PKA reduced sleep duration and delta power, an indicator of sleep needs, whereas PP1 and calcineurin increased them. These enzymes act at neuronal post-synapses, crucial for information transmission in the brain. The research reveals that these enzymes might work competitively to regulate daily sleep duration, marking a critical understanding in molecular sleep regulation. Conducted under the Ueda Biological Timing Project and funded by JST, this study forms part of broader efforts to comprehend human biological time using the model of sleep-wake rhythms.