Abstract
Neurons that synthesize melanin-concentrating hormone (MCH) may modulate arousal and energy homeostasis. The scattered MCH neurons have been difficult to study, as they have no defining morphological characteristics. We have developed a viral approach with AAV for selective long-term reporter gene (GFP) expression in MCH neurons, allowing the study of their cellular physiology in hypothalamic slices. MCH neurons showed distinct membrane properties compared to other neurons infected with the same virus with a cytomegalovirus promoter. Transmitters of extrahypothalamic arousal systems, including norepinephrine, serotonin, and the acetylcholine agonist muscarine, evoked direct inhibitory actions. Orexigenic neuropeptide Y was inhibitory by pre- and postsynaptic mechanisms; an anorexigenic melanocortin agonist had no effect. In contrast, the hypothalamic arousal peptide hypocretin/orexin evoked a direct inward current and increased excitatory synaptic activity and spike frequency in the normally silent MCH neurons. Together, these data support the view that MCH neurons may integrate information within the arousal system in favor of energy conservation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adrenergic alpha-Agonists / pharmacology
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Animals
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Arousal / drug effects
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Arousal / genetics
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Carrier Proteins / pharmacology
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Cytomegalovirus / genetics
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Dependovirus / genetics*
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Energy Metabolism / drug effects
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Energy Metabolism / genetics
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / genetics
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Gene Expression Regulation / genetics*
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Genes, Reporter
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Genetic Vectors / genetics
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Green Fluorescent Proteins
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Hypothalamic Hormones / genetics
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Hypothalamic Hormones / metabolism*
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Hypothalamus / cytology
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Hypothalamus / drug effects
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Hypothalamus / metabolism*
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In Vitro Techniques
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Intracellular Signaling Peptides and Proteins*
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Luminescent Proteins / biosynthesis
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Luminescent Proteins / genetics
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Melanins / genetics
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Melanins / metabolism*
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Membrane Potentials / drug effects
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Membrane Potentials / genetics
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Mice
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Muscarine / pharmacology
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Neural Inhibition / drug effects
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Neural Inhibition / genetics
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Neuropeptide Y / pharmacology
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Neuropeptides / pharmacology
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Orexins
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Pituitary Hormones / genetics
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Pituitary Hormones / metabolism*
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Promoter Regions, Genetic / genetics
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Serotonin / pharmacology
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Synapses / drug effects
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Synapses / metabolism
Substances
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Adrenergic alpha-Agonists
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Carrier Proteins
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Hypothalamic Hormones
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Intracellular Signaling Peptides and Proteins
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Luminescent Proteins
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Melanins
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Neuropeptide Y
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Neuropeptides
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Orexins
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Pituitary Hormones
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Green Fluorescent Proteins
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Serotonin
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melanin-concentrating hormone
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Muscarine