Reversible suppression of circadian-driven locomotor rhythms in mice using a gradual fragmentation of the day-night cycle

Abstract

Circadian rhythms are regulated by molecular clockwork and drive 24-h behaviors such as locomotor activity, which can be rendered non-functional through genetic knockouts of clock genes. Circadian rhythms are robust in constant darkness (DD) but are modulated to become exactly 24 h by the external day-night cycle. Whether ill-timed light and dark exposure can render circadian behaviors non-functional to the extent of genetic knockouts is less clear. In this study, we discovered an environmental approach that led to a reduction or lack in rhythmic 24-h-circadian wheel-running locomotor behavior in mice (referred to as arrhythmicity). We first observed behavioral circadian arrhythmicity when mice were gradually exposed to a previously published disruptive environment called the fragmented day-night cycle (FDN-G), while maintaining activity alignment with the four dispersed fragments of darkness. Remarkably, upon exposure to constant darkness (DD) or constant light (LL), FDN-G mice lost any resemblance to the FDN-G-only phenotype and instead, exhibited sporadic activity bursts. Circadian rhythms are maintained in control mice with sudden FDN exposure (FDN-S) and fully restored in FDN-G mice either spontaneously in DD or after 12 h:12 h light–dark exposure. This is the first study to generate a light–dark environment that induces reversible suppression of circadian locomotor rhythms in mice.