Simple Lighting Manipulations Facilitate Behavioral Entrainment of Mice to 18-h Days

In an invariantly rhythmic world, a robust and stable mammalian circadian clock is presumed to confer fitness advantages. In shift-work or after rapid transmeridian travel, however, a stable clock might be maladaptive and a more flexibly resettable clock may have advantages. The rate at which rodents can adjust to simulated time zone travel and the range of entrainment can be markedly increased through simple light manipulations, namely, by exposing animals to extremely dim light (<0.01 lux) at night or by bifurcating rhythms under 24-h light-dark-light-dark (LDLD) cycles. Here we investigated the separate effects of dim light and bifurcation on the ability of mice to entrain to 18-h days (LD 13:5; T18). Incorporating dim light at night, mice in Experiment 1 were exposed either to LD cycles with photophases that were progressively shortened from LD 19:5 to LD 13:5 or to bifurcating LDLD cycles with photophases that were lengthened from LDLD 7:5:7:5 to LDLD 13:5:13:5. In both cases, wheel-running rhythms were robustly synchronized to T18 and the phase of the free-running circadian rhythm was controlled by the timing of release into constant conditions. In Experiment 2, either dimly illuminated nights or a history of bifurcation without continuing dim light was sufficient to allow behavioral entrainment to T18 whereas previously unbifurcated mice under dark nights failed to entrain to T18. Additionally, concurrent measurement of body temperature rhythms in T24 LDLD revealed them to be bimodal. These studies suggest that the circadian system is markedly more flexible than conventionally thought and that this flexibility can be achieved in a noninvasive and nonpharmacological way. Facilitation of behavioral entrainment to extreme light-dark cycles may have translational potential for human shift-workers.