Multi-oscillator structure of the circadian pacemaker

• Online Access: http://hdl.handle.net/2047/d20009291

Circadian rhythms are an important part of the body's physiological processes. Although circadian rhythms are endogenously generated, they are normally entrained by environmental cycles, most commonly the light/dark (LD) cycle. One important issue is how they are regulated and synchronized within the suprachiasmatic nucleus (SCN), the controlling center in the mammalian brain. Previous studies have shown that mice deficient in an SCN peptide (VIP-/- mice) under constant darkness display disrupted circadian rhythms with a varying phenotype. The extent to which this deficiency affects mice when entrained to LD cycles is less clear. Some effects of the deficiency suggest that mice should entrain more easily to LD cycles while other aspects suggest that entrainment should be more difficult. One test of entrainment not previously examined is the ability of mice to entrain to non-24 hour LD cycles (limits of entrainment). I show that in deficient mice, entrainment is abnormal but possibly more so for a distinct sub-region of the SCN. It is suggested that the core part of the SCN in VIP deficient is able to entrain normally, but that it is then unable to synchronize with the shell region, creating a functional separation of SCN sub-regions. This suggests a role for VIP within the SCN more specific than previously thought. Disrupted sleep cycles are a common characteristic of neurodegenerative disease and mouse models of similar conditions show a reduction of VIP and/or its receptor. Understanding the effect that those changes have on entrainment and how that affects sleep behavior can help in the development of entrainment-based therapy.