Hypothalamic orexin neurons regulate arousal according to energy balance in mice.
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.
Yamanaka
Akihiro
A
Institute of Basic Medical Science, University of Tsukuba, 305-8575, Ibaraki, Japan.
Beuckmann
Carsten T
CT
Willie
Jon T
JT
Hara
Junko
J
Tsujino
Natsuko
N
Mieda
Michihiro
M
Tominaga
Makoto
M
Yagami
Ken ichi
Ki
Sugiyama
Fumihiro
F
Goto
Katsutoshi
K
Yanagisawa
Masashi
M
Sakurai
Takeshi
T
D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000235:genetics*; D001786:Blood Glucose / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D005508:Food Deprivation / Q000502:physiology*; D054439:Ghrelin; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics; D006815:Hunger / Q000187:drug effects / Q000502:physiology*; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology; D008164:Luminescent Proteins; D008297:Male; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000172:deficiency* / Q000235:genetics; D000068797:Orexins; D009924:Organ Culture Techniques; D036361:Peptide Hormones / Q000378:metabolism / Q000494:pharmacology; D011993:Recombinant Fusion Proteins; D009435:Synaptic Transmission / Q000235:genetics; D019076:Transgenes / Q000235:genetics
D001786:Blood Glucose; D002352:Carrier Proteins; D054439:Ghrelin; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin; D008164:Luminescent Proteins; D009479:Neuropeptides; D000068797:Orexins; D036361:Peptide Hormones; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D005947:Glucose