Photic Entrainment ofPeriodMutant Mice is Predicted from Their Phase Response Curves

A fundamental property of circadian clocks is that they entrain to environmental cues. The circadian genes, Period1 and Period2, are involved in entrainment of the mammalian circadian system. To investigate the roles of the Period genes in photic entrainment, we constructed phase response curves (PRC) to light pulses for C57BL/6J wild-type, Per1(-/-), Per2(-/-), and Per3(-/-) mice and tested whether the PRCs accurately predict entrainment to non-24 light-dark cycles (T-cycles) and constant light (LL). The PRCs of wild-type and Per3(-/-) mice are similar in shape and amplitude and have relatively large delay zones and small advance zones, resulting in successful entrainment to 26 h T-cycles (T26), but not T21, with similar phase angles. Per1(-/-) mice have a high-amplitude PRC, resulting in entrainment to a broad range of T-cycles. Per2(-/-) mice also entrain to a wide range of T-cycles because the advance portion of their PRC is larger than wild types. Period aftereffects following entrainment to T-cycles were similar among all genotypes. We found that the ratio of the advance portion to the delay portion of the PRC accurately predicts the lengthening of the period of the activity rhythm in LL. Wild-type, Per1(-/-), and Per3(-/-) mice had larger delay zones than advance zones and lengthened (>24 h) periods in LL, whereas Per2(-/-) mice had delay and advance zones that were equal in size and no period lengthening in LL. Together, these results demonstrate that PRCs are powerful tools for predicting and understanding photic entrainment of circadian mutant mice.