Abstract
Output from the hypothalamic ventromedial nucleus (VMN) is anorexigenic and is supported by the excitatory actions of leptin. The VMN is also highly sensitive to the orexigenic actions of Neuropeptide Y (NPY). We report that NPY robustly inhibits VMN neurons by hyperpolarizing them and decreasing their ability to fire action potentials. This action was mediated by Y(1) receptors coupled to the activation of GIRKs (G-protein-coupled inwardly rectifying potassium channels). Approximately 80% of VMN neurons expressing leptin receptors were sensitive to the actions of NPY, whereas 75% of NPY-sensitive neurons in VMN also responded to glucose by being uniformly inhibited by elevations in glucose. Interestingly, only approximately 36% of NPY-sensitive, leptin receptor b-expressing neurons were also glucosensitive. We suggest that NPY inhibits VMN neurons that are excited by leptin, thereby arresting the anorexigenic tone exerted by VMN neurons. The results further suggest a dynamic interplay between anorexigenic and orexigenic neuromodulators within the VMN to directly affect energy balance.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Action Potentials / drug effects
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Action Potentials / physiology
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Animals
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Appetite / drug effects
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Appetite / physiology*
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Blood Glucose / physiology
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Feeding Behavior / drug effects
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Feeding Behavior / physiology*
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G Protein-Coupled Inwardly-Rectifying Potassium Channels / drug effects
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G Protein-Coupled Inwardly-Rectifying Potassium Channels / metabolism
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Gene Knock-In Techniques
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Green Fluorescent Proteins / genetics
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Leptin / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Neural Inhibition / drug effects
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Neural Inhibition / physiology*
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Neural Pathways / cytology
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Neural Pathways / drug effects
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Neural Pathways / metabolism*
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Neurons / drug effects
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Neurons / metabolism
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Neuropeptide Y / metabolism*
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Neuropeptide Y / pharmacology
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Organ Culture Techniques
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Patch-Clamp Techniques
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Receptors, Leptin / drug effects
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Receptors, Leptin / metabolism
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Receptors, Neuropeptide Y / agonists
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Receptors, Neuropeptide Y / metabolism
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Staining and Labeling
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Ventromedial Hypothalamic Nucleus / cytology
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Ventromedial Hypothalamic Nucleus / drug effects
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Ventromedial Hypothalamic Nucleus / metabolism*
Substances
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Blood Glucose
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G Protein-Coupled Inwardly-Rectifying Potassium Channels
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Leptin
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Neuropeptide Y
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Receptors, Leptin
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Receptors, Neuropeptide Y
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enhanced green fluorescent protein
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neuropeptide Y-Y1 receptor
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Green Fluorescent Proteins