Hypothalamic orexin neurons regulate arousal according to energy balance in mice

Akihiro Yamanaka, Carsten T. Beuckmann, Jon T. Willie, Junko Hara, Natsuko Tsujino, Michihiro Mieda, Makoto Tominaga, Ken Ichi Yagami, Fumihiro Sugiyama, Katsutoshi Goto, Masashi Yanagisawa, Takeshi Sakurai

Research output: Contribution to journalArticlepeer-review

789 Scopus citations


Mammals respond to reduced food availability by becoming more wakeful and active, yet the central pathways regulating arousal and instinctual motor programs (such as food seeking) according to homeostatic need are not well understood. We demonstrate that hypothalamic orexin neurons monitor indicators of energy balance and mediate adaptive augmentation of arousal in response to fasting. Activity of isolated orexin neurons is inhibited by glucose and leptin and stimulated by ghrelin. Orexin expression of normal and ob/ob mice correlates negatively with changes in blood glucose, leptin, and food intake. Transgenic mice, in which orexin neurons are ablated, fail to respond to fasting with increased wakefulness and activity. These findings indicate that orexin neurons provide a crucial link between energy balance and arousal.

Original languageEnglish
Pages (from-to)701-713
Number of pages13
Issue number5
StatePublished - Jun 5 2003


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