Comment on "Differential rescue of light- and food-entrainable circadian rhythms"

Abstract

Fuller et al. (Reports, 23 May 2008, p. 1074) reported that the dorsomedial hypothalamus contains a Bmal1-based oscillator that can drive food-entrained circadian rhythms. We report that mice bearing a null mutation of Bmal1 exhibit normal food-anticipatory circadian rhythms. Lack of food anticipation in Bmal1-/- mice reported by Fuller et al. may reflect morbidity due to weight loss, thus raising questions about their conclusions.

Fig. 1

Activity rhythms of wild-type (A) and Bmal1^−/− (B) mice (17). Each line represents 48 hours, plotted in 20-min bins from the left. Consecutive days are also aligned vertically, that is, the charts are double-plotted. Activity was measured by passive infrared motion sensors mounted 30 cm above each cage. Activity data were normalized to the daily mean and are represented by heavy bars, in quartile heights. During the first 14 days, food was available ad libitum, for 7 days in LD (12-hour photoperiod denoted by yellow shading) and 7 days in constant dark (gray shading). Food restriction schedules began after the horizontal red line and were conducted in constant dark. After 30 hours of food deprivation (FD1), food was available for 8 hours (RF1st.1), then reduced to 6 hours and 4 hours over the next 2 days, respectively. RF1-5 denotes 7-day blocks of 4 hour/day feeding (green shading). Blocks RF4 and 5 are separated by 4 days of ad-lib feeding (green shading) and 30 hours of food deprivation (FD2). (C and D) Group activity profiles from wild-type mice (n = 4) and Bmal1^−/− mice (n = 5), respectively, averaged in 10-min bins over days 22 to 28 (block RF4) of restricted feeding in constant dark. Green shading denotes the 4-hour daily mealtime.