The 24-h organization of modern economy challenges the daily organization of our internal biological rhythms. Under normal conditions, an orchestra of body clocks, conducted by a central pacemaker in the hypothalamus (suprachiasmatic nucleus, SCN) synchronizes specific behavior and physiology to specific times of day, leading to optimal performance. Shift work conditions may reduce synchrony among body clocks, possibly leading to abnormal physiology and reduced cognitive function. Psychological stress, altered hormone levels, cancer risk, and obesity symptoms in shift workers indicate considerable consequences of internal physiological asynchrony. In this project we will keep mice under different shift work schedules to describe the mechanisms of physiological asynchrony and its consequences. Under normal light dark (LD) cycles, neuronal SCN activity is synchronized to the light, while mice are active and feed during the dark phase. Under shift work conditions, we will force feeding and/or locomotor activity in three shifts over the LD cycle. Behavioral, physiological, metabolic, and cognitive effects will be measured in mice exposed to fast advancing, slow advancing, fast delaying, and slow delaying schedules. At the end of a shift, a metabolic balance profile will be established. Electrophysiological SCN activity phase will be measured in vitro, and mice will be assessed for behavioral and feeding rhythms, for liver activity rhythm (bile acids and enzyme metabolites), and melatonin profiles. This circadian hormone was found at lower levels in shift workers and was correlated with their cancer prevalence. To assess the effects of shift work on psychological stress and cognitive performance, mice will be tested for maze learning and anxiety. The combined description of behavioral and physiological effects will provide strong insights in the impact of different shift work schedules on central and peripheral circadian organisation and cognitive performance.