The circadian pacemaker in the cultured suprachiasmatic nucleus from pup mice is highly sensitive to external perturbation

Abstract

The circadian clock in the suprachiasmatic nucleus of the hypothalamus (SCN) entrains to non-photic maternal rhythms in the fetal and neonatal periods of rodents but this capacity disappears in later life. In order to understand the mechanism behind the non-photic entrainment in the early postnatal period, the phase response of the clock gene (Bmal1) expression rhythm to external stimuli was examined in cultured SCN harvested at postnatal day 6. The SCN was obtained from transgenic mice carrying a bioluminescence reporter for Bmal1 expression. Phase-dependent phase shifts of circadian rhythm were detected in the pup as well as in the adult for culture medium exchange but the amount of phase shift was significantly larger in the pup than in the adult SCN. Half of the pup SCNs did not show integrated circadian rhythmicities in the first few days in culture. In pups, the circadian period of Bmal1 expression rhythm was shorter and the amplitude of circadian rhythm was much lower than in adults. It is concluded that the responsiveness of cultured SCN to medium exchange is much larger in pups than in adult mice. Immaturity of the structural organization in the circadian system seems to underlie the high responsiveness of the pup SCN.