UC San Diego

Circadian disruption, specifically in shiftwork, entails significant health risks including metabolic and sleep- related disorders. Most current interventions involve the manipulation of the phase, or timing, of circadian rhythms, while those involving the waveform, or shape, of rhythms have received relatively little attention. The studies in this dissertation characterize behavioral, physiological, and cognitive effects of a novel circadian waveform manipulation, both under steady state conditions and under simulated jet lag paradigms. Here we clearly demonstrate that both a natural, photoperiodic change in waveform, and an artificial, bifurcated circadian waveform confer a more than two-fold advantage in adjustment to 6 equidistant time zones. Further, while mammals in long days typically re-entrain to new light schedules at the rate of ̃1 h/day, we show here that bifurcated animals can entrain to light cycles 12 h apart (i.e., on opposite sides of the world) in three days. Thus, manipulating waveform before phase shifts utilizing only simple changes in the daily pattern of light exposure increases plasticity in this system to an unprecedented extent. Here we also show that the bifurcated entrainment state involves a unique configuration of rhythmic clock genes that is apparently functional and readily-reversible. Recently, bifurcation has been suggested as a potential entrainment state for human shiftworkers. Here we find that bifurcation can be maintained under a simulated rotating shift schedule, and that it does not impair memory, while simulated jet-lag does. Both of these findings of intact learning and memory and resilience to perturbations of the light/dark schedule are key pieces in the applicability of bifurcation as an entrainment state for humans exposed to shiftwork or other challenging schedules