Photoperiod Manipulation Reveals a Light-Driven Component to Daily Patterns of Ventilation in Male C57Bl/6J Mice

Obstructive sleep apnea is a common sleep disorder that increases risk for cardiovascular disease and mortality. The severity of sleep-disordered breathing in obstructive sleep apnea patients fluctuates with the seasons, opening the possibility that seasonal changes in light duration, or photoperiod, can influence mechanisms of breathing. Photoperiod can have profound effects on internal timekeeping and can reshape metabolic rhythms in mammals. While the daily rhythm in ventilation is largely shaped by the metabolic rate, less is known about whether ventilatory rhythms are altered in accordance with metabolism under different photoperiods. Here, we investigate the relationship between ventilation and metabolism under different photoperiods using whole-body plethysmography and indirect calorimetry. We find that the daily timing of ventilation is chiefly synchronized to dark onset and that light cues are important for maintaining daily ventilatory rhythms. Moreover, changes in ventilatory patterns are not paralleled by changes in oxygen consumption, energy expenditure, or respiratory exchange rate under different photoperiods. We conclude that ventilatory patterns are not only shaped by the metabolic rate and circadian timing but are also influenced by other light-driven factors. Collectively, these findings have clinical implications for the seasonal variations in sleep-disordered breathing found in individuals with obstructive sleep apnea

Reduced VIP Expression Affects Circadian Clock Function in VIP-IRES-CRE Mice (JAX 010908)

Circadian rhythms are programmed by the suprachiasmatic nucleus (SCN), which relies on neuropeptide signaling to maintain daily timekeeping. Vasoactive intestinal polypeptide (VIP) is critical for SCN function, but the precise role of VIP neurons in SCN circuits is not fully established. To interrogate their contribution to SCN circuits, VIP neurons can be manipulated specifically using the DNA-editing enzyme Cre recombinase. Although the Cre transgene is assumed to be inert by itself, we find that VIP expression is reduced in both heterozygous and homozygous adult VIP-IRES-Cre mice (JAX 010908). Compared with wild-type mice, homozygous VIP-Cre mice display faster reentrainment and shorter free-running period but do not become arrhythmic in constant darkness. Consistent with this phenotype, homozygous VIP-Cre mice display intact SCN PER2::LUC rhythms, albeit with altered period and network organization. We present evidence that the ability to sustain molecular rhythms in the VIP-Cre SCN is not due to residual VIP signaling; rather, arginine vasopressin signaling helps to sustain SCN function at both intracellular and intercellular levels in this model. This work establishes that the VIP-IRES-Cre transgene interferes with VIP expression but that loss of VIP can be mitigated by other neuropeptide signals to help sustain SCN function. Our findings have implications for studies employing this transgenic model and provide novel insight into neuropeptide signals that sustain daily timekeeping in the master clock