BackgroundCircadian disruptions through frequent transmeridian travel, rotating shift work, and poor sleep hygiene are associated with an array of physical and mental health maladies, including marked deficits in human cognitive function. Despite anecdotal and correlational reports suggesting a negative impact of circadian disruptions on brain function, this possibility has not been experimentally examined.Methodology/Principal FindingsIn the present study, we investigated whether experimental ‘jet lag’ (i.e., phase advances of the light∶dark cycle) negatively impacts learning and memory and whether any deficits observed are associated with reductions in hippocampal cell proliferation and neurogenesis. Because insults to circadian timing alter circulating glucocorticoid and sex steroid concentrations, both of which influence neurogenesis and learning/memory, we assessed the contribution of these endocrine factors to any observed alterations. Circadian disruption resulted in pronounced deficits in learning and memory paralleled by marked reductions in hippocampal cell proliferation and neurogenesis. Significantly, deficits in hippocampal-dependent learning and memory were not only seen during the period of the circadian disruption, but also persisted well after the cessation of jet lag, suggesting long-lasting negative consequences on brain function.Conclusions/SignificanceTogether, these findings support the view that circadian disruptions suppress hippocampal neurogenesis via a glucocorticoid-independent mechanism, imposing pronounced and persistent impairments on learning and memory.

Circadian rhythms impact a variety of behavioral and physiological functions contributing to longevity and successful reproduction. In their natural environments, individuals of a species are faced with a multitude of challenges and the coordination of internal processes and behavior with external pressures has been hypothesized to be an important target of natural selection. Several lines of evidence from cyanobacteria, Drosophila, and plants provide strong support for an important role of the circadian clock in survival and reproductive success. Similarly in mammals, disruptions in circadian function markedly impact reproduction and lifespan. The present review discusses research outlining the proximate and ultimate mechanisms responsible for the central and peripheral control of the reproductive axis. Because precise temporal coordination of the endocrine system is particularly crucial for reproduction by females, the present overview focuses on the role of circadian timing in this sex.

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