Final Report Summary - CLOCKWORK (Work around the clock: effects of shift work on cognitive performance and circadian organization in behavior and physiology) The 'ClockWork' project aims to develop a comprehensive mouse model to study the effects of shift work.The daily organisation of our internal biological rhythms has evolved to adapt our physiology to the night-day rhythms of the environment. Modern society challenges this adaptation in many ways (e.g. artificial light, long distance travelling) and shift work can be considered as the most profound perturbation to internal rhythmical synchronisation. Under normal conditions, an orchestra of body clocks, conducted by a central pacemaker in the hypothalamus (suprachiasmatic nucleus, SCN) synchronises specific behaviour and (neuro)physiology to specific times of day leading to optimal physiological and mental performance. Shift work induced internal desynchronisation may lead to abnormal physiological responses (obesity), reduced cognitive function, and increased risk for somatic and mental disease. Although shift work occurs widely in modern society and the claims of health risks involved are severe, we know surprisingly little about the physiological and neurobiological responses to shift work due to the lack of a comprehensive animal model.Central aimWe will develop a comprehensive mouse model for shift work, which will be used to describe the mechanisms of internal desynchronisation between the central circadian pacemaker (SCN) and hormonal and peripheral rhythms.Central approachMice were forced to be active and awake by scheduled running wheel activity following a forward or backward rotating shifts either fast (3 days per shift) or slow (10 days per shift).Effects were measured: A) in the central nervous system, especially the SCN (the site of the biological circadian clock); B) metabolism and physiology; C) rhythms in peripheral organs; and D) behaviour and cognitive performance.OutcomeWe found that the circadian system and metabolism are intricately connected. Mice that are normally active during the night (and sleep during the day), will become day active (and sleep during the night) when they have to work for their food. This is not because the central circadian clock (SCN) has changed its activity pattern, but because it has lost its influence on a, yet unknown, circadian pacemaker that drives activity.