ABSTRACT
Disruptions of circadian rhythms have been linked to a wide range of pathologies from sleep disorders to cancer. The extent to which disruptions of circadian rhythms during development contribute to later conditions is not known. The present study tested the hypothesis that functional properties of the central circadian pacemaker, the suprachiasmatic nucleus (SCN), are affected by abnormal entrainment during development. The SCN is specialized for the generation of robust rhythms, for direct and indirect output to physiological and behavioral systems, and for entrainment to light/dark cycles via direct retinal input. It consists of thousands of neurons and glia with distinct phenotypes and has subdivisions delineated by both anatomical and functional criteria. In rodents, SCN rhythms develop within days after SCN cells are produced and before many other aspects of differentiation, such as synaptogenesis, are complete. We demonstrated that around the time of birth, the hamster SCN in vivo can undergo repeated phase shifts by a dopamine D(1) receptor agonist (SKF-38393). For 2 days before and 2 days after birth, one group of hamsters received regular exposure to the drug at the same time of day, while another group was exposed at varying times to induce repeated phase shifts. Free-running and entrained activity rhythms were compared between the groups at different ages after weaning. Repeated phase shifts during SCN development had a significant effect on free-running period measured immediately after weaning. This effect was eliminated by subsequent entrainment to a light/dark cycle, indicating that the effect was not permanent. These and other results suggest that SCN development required for functional properties such as free-running period is resilient to perturbation.