Food-entrained patterns in orexin cells reveal subregion differential activation

Rats under a restricted feeding schedule develop food anticipatory activity 2-3h prior food access, characterized by increased arousal, foraging and exploratory behavior. This anticipatory behavior is not observed when rodents are allowed ad libitum food access and reappears for several cycles when food-entrained animals are fasted. Previously we reported that food entrainment also produces increased expression of c-Fos protein in the dorsomedial nucleus (DMH), in the perifornical area (PeF) and in the lateral hypothalamic area (LH) anticipating food intake. These hypothalamic structures contain abundant orexin (ORX) producing neurons and promote arousal, reward and metabolic balance, thus we explored the participation of the orexinergic system in food-entrainment by evaluating in food entrained rats (RF) the expression of c-Fos in ORX cells in anticipation, during and after food access, and in rats exhibiting persistent activation in fasting after interruption of the food-entrainment protocol (RF-Fast). Data were compared with ad libitum controls and with a 22-h fasted group. RF rats exhibited a food-entrained rhythm of c-Fos in ORX cells in the DMH, LH and PeF with highest levels at the time of meal delivery and after food ingestion. In RF-Fast rats the food-entrained pattern of ORX cells persisted in the PeF and LH and partially in the DMH, which in addition exhibited an earlier activation. We conclude that ORX cells in PeF and LH exhibit self sustained oscillations driven by food-entrainment, whereas the DMH may mediate arousal mechanisms that elicit anticipatory activity.