Two Coupled Circadian Oscillators Are Involved in Nonphotic Acceleration of Reentrainment to Shifted Light Cycles in Mice

The onset and offset of an activity band in the circadian behavioral rhythm are known to differentially reentrain to shifted light-dark cycles (LD). Differential reentrainment could be explained by different light responsivities of circadian oscillators underlying these phase-markers. In contrast, reentrainment is accelerated by exposure to nonphotic time cues such as timed wheel-running. However, the relationship between the 2 oscillators and nonphotic acceleration of reentrainment is largely unknown. We examined phase-shifts of the mouse behavioral rhythm in response to an 8-h phase-advanced shift of LD and effects of behavioral interventions: maintained in a home cage (HC), exposed to a running wheel (RW) in HC (HC+RW), transferred to a new cage (NC), and exposed to RW in NC (NC+RW). Each intervention was given for 3h from the beginning of the shifted dark period and repeated for 4 days. Following the last dark period, the mice were released into constant darkness (DD). As a result, activity onset and offset were differentially phase-shifted. The activity onset on the first day of DD (DD1) was phase-advanced from the baseline slightly in HC and HC+RW, substantially in NC+RW, but not significantly in NC. The amount of phase-shift was significantly larger in the NC+RW than in the other groups. In contrast, the activity offset was significantly advanced in all groups by 6 to 8 h. The differential phase-shifts resulted in shortening of the activity band (α compression). The α compression was gradually relieved upon exposure to DD (α decompression), and the activity band finally became stable. Interestingly, the magnitude of phase-shifts of activity offset, but not of activity onset, in the following DD was negatively correlated with the extent of α compression in DD1. These findings indicate that the 2 circadian oscillators underlying activity onset and offset are involved in asymmetric phase-shifts and nonphotic acceleration of reentrainment