Food anticipatory behavior (FAA) is induced by limiting access to food for a few hours daily. Animals anticipate this scheduled meal event even without the suprachiasmatic nucleus (SCN), the biological clock. Consequently, a food-entrained oscillator has been proposed to be responsible for meal time estimation. Recent studies suggested the dorsomedial hypothalamus (DMH) as the site for this food-entrained oscillator, which has led to considerable controversy in the literature. Herein we demonstrate by means of c-Fos immunohistochemistry that the neuronal activity of the suprachiasmatic nucleus (SCN), which signals the rest phase in nocturnal animals, is reduced when animals anticipate the scheduled food and, simultaneously, neuronal activity within the DMH increases. Using retrograde tracing and confocal analysis, we show that inhibition of SCN neuronal activity is the consequence of activation of GABA-containing neurons in the DMH that project to the SCN. Next, we show that DMH lesions result in a loss or diminution of FAA, simultaneous with increased activity in the SCN. A subsequent lesion of the SCN restored FAA. We conclude that in intact animals, FAA may only occur when the DMH inhibits the activity of the SCN, thus permitting locomotor activity. As a result, FAA originates from a neuronal network comprising an interaction between the DMH and SCN. Moreover, this study shows that the DMH-SCN interaction may serve as an intrahypothalamic system to gate activity instead of rest overriding circadian predetermined temporal patterns. P hysiology and behavior of all mammals is organized in an alternating pattern of rest and activity cycles, whereby the endogenous and light-induced daily neuronal activity of the suprachiasmatic nucleus (SCN) signals rest in nocturnal rodents and activity in diurnal primates, such as humans (1, 2). Restricting food access to a short and predictable episode during the rest phase changes this behavioral pattern, such that an animal becomes active and for up to several hours anticipates the upcoming feeding event. This food anticipatory activity (FAA) is even exhibited without the known circadian oscillator, the SCN (3), and thus may rely on a different circadian pacemaker.In search of the location of this so-called "food entrained oscillator" (FEO), two recent studies have claimed that its position is within the dorsomedial nucleus of the hypothalamus (DMH) (4, 5). The designation of the DMH as master clock for food entrainment is, however, controversial because some groups reported unimpaired FAA despite large lesions of the DMH (6, 7); others have shown that lesions of the DMH disturb and diminish the intensity of FAA (6). The possible participation of other brain structures in FAA is evident from studies that demonstrate modulation of neuronal activity and induction of clock-gene rhythmicity in hypothalamic and limbic structures by feeding schedules (8-11). Thus, it has been suggested that FAA depends on a multioscillatory system comprised of a complex and redundant neuronal netwo...

Timing of metabolic processes is crucial for balanced physiology; many studies have shown the deleterious effects of untimely food intake. The basis for this might be an interaction between the arcuate nucleus (ARC) as the main integration site for metabolic information and the suprachiasmatic nucleus (SCN) as the master clock. Here we show in male rats that the SCN influences ARC daily neuronal activity by imposing a daily rhythm on the α-MSH neurons with a peak in neuronal activity at the end of the dark phase. Bilateral SCN lesions showed a complete disappearance of ARC neuronal rhythms and unilateral SCN lesions showed a decreased activation in the ARC at the lesioned side. Moreover light exposure during the dark phase inhibited ARC and α-MSH neuronal activity. The daily inhibition of ARC neuronal activity occurred in light-dark conditions as well as in dark-dark conditions, demonstrating the inhibitory effect to be mediated by increased SCN (subjective) day neuronal activity. Injections into the SCN with the neuronal tracer cholera toxin B showed that α-MSH neurons receive direct projections from the SCN. The present study demonstrates that the SCN activates and possibly also inhibits depending on the moment of the circadian cycle ARC α-MSH neurons via direct neuronal input. The persistence of these activity patterns in fasted animals demonstrates that this SCN-ARC interaction is not necessarily satiety associated but may support physiological functions associated with changes in the sleep-wake cycle.