Abstract
It is widely agreed that breathing is subject to circadian regulation. Circadian differences in respiratory physiology significantly impact a number of diseases including sleep apnea, asthma, and seizure-induced death. The effect of time of day on breathing has been previously characterized; however, an endogenous free-running respiratory rhythm in mammals has not previously been described. Furthermore, it is assumed that circadian rhythms in breathing are dependent on the hypothalamic suprachiasmatic nucleus (SCN), the home of the mammalian central circadian oscillator, but this has not been shown experimentally. The breathing of mice was monitored during wakefulness using whole body plethysmography at six times of day while housed under light-dark conditions and at six circadian phases while housed under constant darkness. Respiratory frequency and minute ventilation, but not tidal volume, were significantly higher during the active phase in both entrained and free-running conditions. To determine whether circadian regulation of breathing requires the SCN, in separate sets of animals this structure was electrolytically lesioned bilaterally or a sham surgery was performed, and breathing was measured at six different time points. Time-dependent oscillations in breathing were lost in SCN-lesioned animals, but not those subjected to sham surgery. These results suggest that breathing is subject to circadian regulation via the SCN. Mechanistic insights into the circadian regulation of breathing may lead to targeted interventions to reduce the morbidity and mortality associated with diseases with respiratory pathophysiology.NEW & NOTEWORTHY It has long been appreciated that breathing is altered by time of day. This study demonstrates that rhythmicity in breathing persists in constant darkness but is dependent on the suprachiasmatic nucleus in the hypothalamus. Understanding circadian rhythms in breathing may be important for the treatment and prevention of diseases such as sleep apnea and sudden unexpected death in epilepsy.