What keeps us awake? The role of clocks and hourglasses, light, and melatonin.

What is it that keeps us awake? Our assumption is that we consciously control our daily activities including sleep-wake behavior, as indicated by our need to make use of an alarm clock to wake up in the morning in order to be at work on time. However, when we travel across multiple time zones or do shift work, we realize that our intentionally planned timings to rest and to remain active can interfere with an intrinsic regulation of sleep/wake cycles. This regulation is driven by a small region in the anterior hypothalamus of the brain, termed as the "circadian clock". This clock spontaneously synchronizes with the environmental light-dark cycle, thus enabling all organisms to adapt to and anticipate environmental changes. As a result, the circadian clock actively gates sleep and wakefulness to occur in synchrony with the light-dark cycles. Indeed, our internal clock is our best morning alarm clock, since it shuts off melatonin production and boosts cortisol secretion and heart rate 2-3h prior awakening from Morpheus arms. The main reason most of us still use artificial alarm clocks is that we habitually carry on a sleep depth and/or the sleep-wake timing is not ideally matched with our social/work schedule. This in turn can lead hourglass processes, as indexed by accumulated homeostatic sleep need over time, to strongly oppose the clock. To add to the complexity of our sleep and wakefulness behavior, light levels as well as exogenous melatonin can impinge on the clock, by means of their so-called zeitgeber (synchronizer) role or by acutely promoting sleep or wakefulness. Here we attempt to bring a holistic view on how light, melatonin, and the brain circuitry underlying circadian and homeostatic processes can modulate sleep and in particular alertness, by actively promoting awakening/arousal and sleep at certain times during the 24-h day.