Integrative coordination of circadian mammalian diversity: neuronal networks and peripheral clocks

Diverse circadian rhythms are generated, maintained and/or coordinated by brain structures constituting the circadian timing system. However, the mechanisms underlying the variety in activity types and circadian rhythm phases and amplitudes are currently unknown. We address this problem by comparing rhythms in diurnal and nocturnal mammals, while focusing on alterations not involving the central circadian oscillator. The circadian rhythms are divided into two groups: activity-independent and activity-related. The rhythms in the first group have similar acrophases in all mammals and are anticipated to function as an internal zeitgeber (time giver). Analysis of activity-related circadian rhythms in behavior, blood pressure (BP) and renal excretion suggests separate mechanisms in their regulation in addition to the central suprachiasmatic nuclei-located circadian oscillator. We propose that: (a) a passive hypothalamic oscillator coordinates the phases and underlies the high amplitude of behavioral circadian rhythms; (b) a separate rostral hypothalamic network participates in the regulation of the low-amplitude circadian BP rhythm; and (c) a circadian oscillator in the kidney generates electrolyte excretion rhythms. A model is offered where the overt activity is determined by the phase-relationship between the circadian and the passive hypothalamic oscillator. Specific brain structures or peripheral circadian oscillators integrate circadian and other signals for different activity-related circadian rhythms. The hypothalamic structures implicated in regulation of behavioral and blood pressure rhythms belong to the circadian timing system since they underlie circadian rhythms diversity. The same hypothalamic areas selectively modulate circadian rhythms in response to homeostatic stimuli or stress without engaging the circadian oscillator.