Abstract
Orexins (OX), also called hypocretins, are bioactive peptides secreted from glucose-sensitive neurons in the lateral hypothalamus linking appetite, arousal and neuroendocrine-autonomic control. Here, OX-A was found to cause a slow-onset long-term potentiation of synaptic transmission (LTPOX) in the hippocampus of young adult mice. LTPOX was induced at Schaffer collateral-CA1 but not mossy fiber-CA3 synapses, and required transient sharp wave-concurrent population field-burst activity generated by the autoassociative CA3 network. Exogenous long theta-frequency stimulation of Schaffer collateral axons erased LTPOX in intact hippocampal slices but not mini slices devoid of the CA3 region. Pharmacological analysis revealed that LTPOX requires co-activation of ionotropic and metabotropic glutamatergic, GABAergic, as well as noradrenergic and cholinergic receptors. Together these data indicate that OX-A induces a state-dependent metaplasticity in the CA1 region associated with sharp-wave and theta rhythm activity as well as glutamatergic, GABAergic, aminergic, and cholinergic transmission. Thus, orexins not only regulate arousal threshold and body weight but also threshold and weight of synaptic connectivity, providing a molecular prerequisite for homeostatic and behavioral state-dependent control of neuronal plasticity and presumably memory functions.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / metabolism
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Action Potentials / drug effects
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Action Potentials / physiology
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Animals
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Carrier Proteins / metabolism*
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Carrier Proteins / pharmacology
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Glutamic Acid / metabolism
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Hippocampus / cytology
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Hippocampus / metabolism*
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In Vitro Techniques
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Intracellular Signaling Peptides and Proteins*
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Long-Term Potentiation / drug effects
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Long-Term Potentiation / physiology
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Male
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Mice
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Mice, Inbred C57BL
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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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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology*
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Neuropeptides / metabolism*
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Neuropeptides / pharmacology
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Neurotransmitter Agents / metabolism*
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Norepinephrine / metabolism
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Orexin Receptors
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Orexins
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / metabolism
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Receptors, G-Protein-Coupled
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Receptors, Neuropeptide
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Receptors, Neurotransmitter / drug effects
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Receptors, Neurotransmitter / metabolism
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
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Theta Rhythm* / drug effects
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gamma-Aminobutyric Acid / metabolism
Substances
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Carrier Proteins
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Intracellular Signaling Peptides and Proteins
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Neuropeptides
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Neurotransmitter Agents
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Orexin Receptors
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Orexins
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Receptors, G-Protein-Coupled
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Receptors, Neuropeptide
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Receptors, Neurotransmitter
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Glutamic Acid
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gamma-Aminobutyric Acid
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Acetylcholine
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Norepinephrine