The molecular clockwork in mammals involves various clock genes with specific temporal expression patterns. Synchronization of the master circadian clock located in the suprachiasmatic nucleus (SCN) is accomplished mainly via daily resetting of the phase of the clock by light stimuli. Phase shifting responses to light are correlated with induction of Per1, Per2 and Dec1 expression and a possible reduction of Cry2 expression within SCN cells. The timing of peripheral oscillators is controlled by the SCN when food is available ad libitum. Time of feeding, as modulated by temporal restricted feeding, is a potent 'Zeitgeber' (synchronizer) for peripheral oscillators with only weak synchronizing influence on the SCN clockwork. When restricted feeding is coupled with caloric restriction, however, timing of clock gene expression is altered within the SCN, indicating that the SCN function is sensitive to metabolic cues. The components of the circadian timing system can be differentially synchronized according to distinct, sometimes conflicting, temporal (time of light exposure and feeding) and homeostatic (metabolic) cues.

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In mammals, the suprachiasmatic nuclei (SCN) are the site of the master circadian pacemaker whose molecular core mechanism is based on interlocking transcriptional/translational feedback loops involving clock genes. Among clock genes, Per1 and Per2 are important for both the maintenance of circadian rhythmicity and entrainment to light cues. Several circadian rhythms (e.g., locomotor activity) present opposite patterns in diurnal and nocturnal species. To test whether a differential cellular expression of clock genes in the SCN could constitute the neural substrate leading to diurnal or nocturnal behavior, we identified, by single or double non-radioactive hybridizations, the phenotype of neurons expressing Per1 and Per2 during the day in a diurnal species, Arvicanthis ansorgei, and in a nocturnal species, the rat (Rattus norvegicus). We show that in both species, expression of Per1 and Per2 is mostly restricted to the dorsomedial part of the SCN, often coexpressed with arginine vasopressin (AVP). A few vasoactive intestinal polypeptide (VIP) neurons were also shown to express Per1 and Per2. This differential expression of Per1 and Per2 in AVP and VIP neurons is more distinct in A. ansorgei than in the rat. Thus, our data suggest a major role for the dorsomedial part of the SCN in the maintenance of circadian rhythmicity. Furthermore, the similar diurnal pattern of Per1 and Per2 expression in diurnal and nocturnal rodents suggests that the circadian organization of locomotor activity rhythms probably relies on differential cellular integration mechanisms downstream of the clock.

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