Circadian Regulation in Diurnal Mammals: Neural Mechanisms and Implications in Translational Research.

Diurnal and nocturnal mammals have evolved unique behavioral and physiological adaptations to optimize survival for their day- or night-active lifestyle. The mechanisms underlying the opposite activity patterns are not fully understood but likely involve the interplay between the circadian time-keeping system and various arousal- or sleep-promoting factors, e.g., light or melatonin. Although the circadian systems between the two chronotypes share considerable similarities, the phase relationships between the principal and subordinate oscillators are chronotype-specific. While light promotes arousal and wakefulness in diurnal species like us, it induces sleep in nocturnal ones. Similarly, melatonin, the hormone of darkness, is commonly used as a hypnotic in humans but is secreted in the active phase of nocturnal animals. Thus, the difference between the two chronotypes is more complex than a simple reversal, as the physiological and neurological processes in diurnal mammals during the day are not equivalent to that of nocturnal ones at night. Such chronotype differences could present a significant translational gap when applying research findings obtained from nocturnal rodents to diurnal humans. The potential advantages of diurnal models are being discussed in a few sleep-related conditions including familial natural short sleep (FNSS), obstructive sleep apnea (OSA), and Smith-Magenis syndrome (SMS). Considering the difference in chronotype, a diurnal model will be more adequate for revealing the physiology and physiopathology pertaining to human health and disease, especially in conditions in which circadian rhythm disruption, altered photic response, or melatonin secretion is involved. We hope the recent advances in gene editing in diurnal rodents will promote greater utility of the diurnal models in basic and translational research.