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Title

Opposite effects of noradrenaline and acetylcholine upon hypocretin/orexin versus melanin concentrating hormone neurons in rat hypothalamic slices

Authors
Machard, D.
Jones, B. E.
Published in Neuroscience. 2005, vol. 130, no. 4, p. 807-811
Abstract Hypocretin/orexin (Hcrt/Orx) and melanin concentrating hormone (MCH) are peptides contained in overlapping cell groups of the lateral hypothalamus and commonly involved in regulating sleep-wake states and energy balance, though likely in different ways. To see if these neurons are similarly or differentially modulated by neurotransmitters of the major brainstem arousal systems, the effects of noradrenaline (NA) and carbachol, a cholinergic agonist, were examined on identified Hcrt/Orx and MCH neurons in rat hypothalamic slices. Whereas both agonists depolarized and excited Hcrt/Orx neurons, they both hyperpolarized MCH neurons by direct postsynaptic actions. According to the activity profiles of the noradrenergic locus coeruleus and cholinergic pontomesencephalic neurons across the sleep-waking cycle, the Hcrt/Orx neurons would be excited by NA and acetylcholine (ACh) and thus active during arousal, whereas the MCH neurons would be inhibited by NA and ACh and thus inactive during arousal while disinhibited and possibly active during slow wave sleep. According to the present pharmacological results, Hcrt/Orx neurons may thus stimulate arousal in tandem with other arousal systems, whereas MCH neurons may function in opposition with other arousal systems and thus potentially dampen arousal to promote sleep.
Keywords Acetylcholine/pharmacology/ physiologyAction Potentials/drug effects/physiologyAnimalsArousal/drug effects/physiologyCholinergic Agonists/pharmacologyHypothalamic Area, Lateral/cytology/drug effects/ metabolismHypothalamic Hormones/ metabolismIntracellular Signaling Peptides and Proteins/ metabolismLocus Coeruleus/physiologyMelanins/ metabolismModels, NeurologicalNeural Inhibition/drug effects/physiologyNeural Pathways/cytology/drug effects/metabolismNeurons/drug effects/ metabolismNeuropeptides/ metabolismNorepinephrine/pharmacology/ physiologyOrgan Culture TechniquesPatch-Clamp TechniquesPedunculopontine Tegmental Nucleus/physiologyPituitary Hormones/ metabolismRatsRats, Sprague-DawleySleep/physiologySynaptic Transmission/drug effects/physiology
Stable URL http://archive-ouverte.unige.ch/unige:10178
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PMID: 15652980
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