illustrates the key behavioral deficits exhibited by the VIP-deficient mice (see Colwell et al., 2003). The black bars represent the daily wheel running activity with successive days plotted one on top of the other. WT mice (left panel) exhibit stable activity patterns in an LD cycle. When released into DD on day 8, the mice exhibit a period of ≈23.5 hrs. Exposure to a brief light pulse at CT 16 (asterisk) will reset the phase of the activity cycle. VIP KO mice (right panel) in a LD cycle are entrained though activity onset is variable compared to controls. When placed into DD, the mice start their activity from a phase 8 to 10 hrs earlier compared to WT. The period of the activity rhythm is ≈22.5 hrs. Many, but not all of the Vip −/− mice, eventually become arrhythmic in DD. The Vipr2 −/− mice exhibit a similar phenotype (see Harmar et al., 2002). Furthermore, VIP KO mice fail to shift their behavioral rhythms in response to a phase-delaying light pulse during early subjective night, as indicated by the yellow asterisk.