While it has long been known that activity in neural networks in sleep differs from activity during waking hours. EEG recordings have revealed patterns of activity oscillations associated with deep (non-REM) sleep and rapid eye movement (REM) sleep. However, it remains unclear how transitions from wake to sleep and from sleep to wake are controlled. One hypothesis is that there are sleep-inducing substances that accumulate during waking hours and then reach a certain tipping point that causes sleep. However, such a sleep substance has not been identified. Genes regulating the cellular circadian clock are implicated but operate on too slow a time scale to explain wake – sleep and wake – sleep transitions. University of Tokyo professor Hiroki Ueda has accumulated evidence for a different mechanism of sleep regulation in which calcium functions as a master regulator by virtue of its effects on phosphorylation of ion channels that regulate neuronal excitability. In this episode I talk with Hiro about his elegant experiments that use cutting-edge technologies to manipulate calcium-regulated kinases (CaMKII alpha and beta) in forebrain neurons while quantifying sleep and wakefulness by continuous monitoring of breathing patterns. Hiro also talks about the development in his laboratory of next generation single-cell genetics and whole-brain single cell imaging technologies and their broad applications in neuroscience research.

LINKS Review articles https://www.sciencedirect.com/science... https://pmc.ncbi.nlm.nih.gov/articles...

Whole brain single-cell atlas of neural activity https://www.science.org/doi/10.1126/s...

Competition between kinases and phosphatases in sleep-wake cycles https://www.nature.com/articles/s4158...