Rapid down-regulation of mammalian Period genes during behavioral resetting of the circadian clock

The pervasive role of circadian clocks in regulating physiology and behavio r is widely recognized, Their adaptive value is their ability to be entrain ed by environmental cues such that the internal circadian phase is a reliab le predictor of solar time, In mammals, both light and nonphotic behavioral cues can entrain the principal oscillator of the hypothalamic suprachiasma tic nuclei (SCN). However, although light can advance or delay the clock du ring circadian night, behavioral events trigger phase advances during the s ubjective day, when the clock is insensitive to light. The recent identific ation of Period (Per) genes in mammals, homologues of dperiod, which encode s a core element of the circadian clockwork in Drosophila, now provides the opportunity to explain circadian timing and entrainment at a molecular lev el. In mice, expression of mPer1 and mPer2 in the SCN is rhythmic and acute ly up-regulated by light, Moreover, the temporal relations between mRNA and protein cycles are consistent with a clock based on a transcriptional/tran slational feedback loop. Here we describe circadian oscillations of Per1 an d Per2 in the SCN of the Syrian hamster, showing that PER1 protein and mRNA cycles again behave in a manner consistent with a negative-feedback oscill ator. Furthermore, we demonstrate that nonphotic resetting has the opposite effect to light: acutely down-regulating these genes. Their sensitivity to nonphotic resetting cues supports their proposed role as core elements of the circadian oscillator. Moreover, this study provides an explanation at t he molecular level for the contrasting but convergent effects of photic and nonphotic cues on the clock.