Food anticipation in Bmal1-/- and AAV-Bmal1 rescued mice: a reply to Fuller et al

Abstract

Evidence that circadian food-anticipatory activity and temperature rhythms are absent in Bmal1 knockout mice and rescued by restoration of Bmal1 expression selectively in the dorsomedial hypothalamus was published in 2008 by Fuller et al and critiqued in 2009 by Mistlberger et al. Fuller et al have responded to the critique with new information. Here we update our critique in the light of this new information. We also identify and correct factual and conceptual errors in the Fuller et al response. We conclude that the original results of Fuller et al remain inconclusive and fail to clarify the role of Bmal1 or the dorsomedial hypothalamus in the generation of food-entrainable rhythms in mice.

Figure 1

Mean daily activity counts detected by infrared (IR) motion sensors and by intraperitoneal transponders (e-mitters) in the same adult male rats (n = 11 DMH sham lesions and n = 5 unoperated controls, combined; data from Mistlberger et al [12]). The motion sensors were positioned above the middle of the cage, as in [12,15]. A, D. Mean counts during hours 3–5 of the light period, corresponding to the time that food-anticipatory activity appears when food is restricted to hours 6–10. B, E. Activity during hours 6–10 of the light period, corresponding to mealtime during restricted feeding. C, F. Total daily activity excluding hours 3–10 of lights on (3 h premeal and 4 h mealtime). Abbreviations: Adlib denotes baseline days with food available ad-libitum. 'D' denotes days when food was not provided (also indicated by arrows below panel C). ZT denotes 'zeitgeber time', referring to the number of hours after lights-on each day (ZT0 by convention). Days when food was restricted to ZT6–10 are further identified by the dotted line box in each panel.