Forebrain oscillators ticking with different clock hands.

Clock proteins like PER1 and PER2 are expressed in the brain, but little is known about their functionality outside the main suprachiasmatic clock. Here we show that PER1 and PER2 were neither uniformly present nor identically phased in forebrain structures of mice fed ad libitum. Altered expression of the clock gene Cry1 was observed in respective Per1 or Per2 mutants. In response to hypocaloric feeding, PERs timing was not markedly affected in few forebrain structures (hippocampus). In most other forebrain oscillators, including those expressing only PER1 (e.g., dorsomedial hypothalamus), PER2 (e.g., paraventricular hypothalamus) or both (e.g., paraventricular thalamus), PER1 was up-regulated and PER2 largely phase-advanced. Cry1 expression was selectively modified in the forebrain of Per mutants challenged with hypocaloric feeding. Our results suggest that there is not one single cerebral clock, but a system of multiple brain oscillators ticking with different clock hands and differentially sensitive to nutritional cues.