Exercise and the Neural Circadian System

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Good sleep habits and regular physical exercise are a cornerstone of good health and longevity. The sleep-wake cycle is organised by the brain's daily or circadian clock. Cells of this brain area contain a molecular clock but must talk to each other to produce a unified ~24h output that controls other brain areas as well as body organs. These individual clock cells communicate using special brain chemicals called neuropeptides, each of which has its own role in timekeeping. Ordinarily, brain clock cells are reset by daylight, but interestingly, in a mouse model in which the brain clock was weakened by through the absence of a particular neuropeptide signal, we found that regular daily physical exercise was much more potent than light. In our work, we found that voluntary scheduled exercise in a running-wheel (6h/day) synchronises the clock cells and promotes stable ~24h rest-activity rhythms. This intriguing effect of exercise was absent in mice in which the molecular clock was deleted from all cells of the brain and body. Unfortunately, we do not know if physical exercise can compensate for the loss of other kinds of neuropeptides or the absence of the molecular clock in particular types of neuropeptide cells in brain clock. We also do not know if other areas of the brain receiving timekeeping signals from the brain clock contribute to these restorative actions of exercise. In this grant we shall address these important gaps in our knowledge and determine how voluntary physical exercise can improve synchronisation in the brain to promote well-being.