Melatonin, the pineal gland, and circadian rhythms.

Amniote circadian organization derives from the interactions of circadian oscillators and photoreceptors located in the hypothalamic suprachiasmatic nuclei (SCN), the pineal gland, and the eyes. In mammals, circadian organization is dominated by the SCN, which serve as "master pacemakers" in the control of a wide array of behavioral and physiological rhythms (including locomotion, sleep-wake, thermoregulation, cardiovascular function, and many endocrine processes). Among the rhythms under SCN control in mammals are the circadian synthesis and secretion of the pineal hormone melatonin, which relies on a multisynaptic pathway via the sympathetic nervous system to maintain and entrain rhythmicity in this hormone. Several studies have indicated that pineal melatonin feeds back on SCN rhythmicity to modulate circadian patterns of activity and other processes. However, the nature and system-level significance of this feedback are unknown. Recently published work indicates that although pinealectomy does not affect rat circadian rhythms in light-dark cycles or constant darkness, wheel-running activity rhythms are severely disrupted in constant light. These data suggest that either (1) pineal feedback regulates the light sensitivity of the SCN, and/or (2) it affects coupling among circadian oscillators within the SCN or between the SCN and its output. Research in our laboratory is currently addressing each of these hypotheses.