Irregular light schedules disrupt daily rhythms and dysregulate genes involved in neuroplasticity, motivation, and stress responses.

Synchronisation of internal biological rhythms with external light-dark cycles is crucial for proper function and survival of the organisms, however modern life often imposes irregular light exposure, disrupting these internal clocks. This study investigated the effects of short-term shifted light-dark cycles on mice daily rhythmicity, and whether these alterations trigger molecular and behavioural changes. We evaluated locomotor activity as well as different behavioural domains and gene expression in the hypothalamus and medial prefrontal cortex. Despite non prominent behavioural impairments, such as anxiety or cognitive deficits, we observed a decreased complexity of locomotor activity patterns of the mice subjected to disrupted light-dark cycles. Molecular alterations included dysregulations in oscillations of core clock genes (Cry2, Per2) and region-dependent disruptions in expression of genes involved in neuroplasticity, neurotransmission, motivation, and stress responses, including Th, Drd1, Gria1&2, Oprk1 and Oxtr. Our study reveals that even brief light cycle shifts can disrupt circadian regulation at the molecular level, despite minimal behavioural changes. This molecular-behavioural discrepancy may suggest a complex adaptive response to drastic short-term light perturbations. Understanding the complex interplay between external light cues and internal biological rhythms regulation is crucial for mitigating the negative consequences of irregular light exposure on physiological processes and overall well-being.