Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arousal / drug effects
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Arousal / genetics*
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Blood Glucose / drug effects
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Blood Glucose / physiology
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Carrier Proteins / genetics
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Energy Metabolism / drug effects
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Energy Metabolism / genetics*
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Exploratory Behavior / drug effects
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Exploratory Behavior / physiology
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Extracellular Space / metabolism
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Food Deprivation / physiology*
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Ghrelin
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Glucose / metabolism
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Glucose / pharmacology
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Green Fluorescent Proteins
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Homeostasis / drug effects
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Homeostasis / genetics
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Hunger / drug effects
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Hunger / physiology*
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Hypothalamus / cytology
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Hypothalamus / drug effects
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Hypothalamus / metabolism*
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Intracellular Signaling Peptides and Proteins*
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Leptin / metabolism
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Leptin / pharmacology
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Luminescent Proteins
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Male
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Membrane Potentials / genetics
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Mice
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Mice, Transgenic
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Neuropeptides / deficiency*
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Neuropeptides / genetics
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Orexins
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Organ Culture Techniques
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Peptide Hormones / metabolism
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Peptide Hormones / pharmacology
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Recombinant Fusion Proteins
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Synaptic Transmission / genetics
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Transgenes / genetics
Substances
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Blood Glucose
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Carrier Proteins
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Ghrelin
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Intracellular Signaling Peptides and Proteins
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Leptin
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Luminescent Proteins
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Neuropeptides
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Orexins
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Peptide Hormones
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Recombinant Fusion Proteins
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Green Fluorescent Proteins
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Glucose