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      The waking brain: an update

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          Abstract

          Wakefulness and consciousness depend on perturbation of the cortical soliloquy. Ascending activation of the cerebral cortex is characteristic for both waking and paradoxical (REM) sleep. These evolutionary conserved activating systems build a network in the brainstem, midbrain, and diencephalon that contains the neurotransmitters and neuromodulators glutamate, histamine, acetylcholine, the catecholamines, serotonin, and some neuropeptides orchestrating the different behavioral states. Inhibition of these waking systems by GABAergic neurons allows sleep. Over the past decades, a prominent role became evident for the histaminergic and the orexinergic neurons as a hypothalamic waking center.

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          Most cited references130

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          Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.

          The hypothalamus plays a central role in the integrated control of feeding and energy homeostasis. We have identified two novel neuropeptides, both derived from the same precursor by proteolytic processing, that bind and activate two closely related (previously) orphan G protein-coupled receptors. These peptides, termed orexin-A and -B, have no significant structural similarities to known families of regulatory peptides. prepro-orexin mRNA and immunoreactive orexin-A are localized in neurons within and around the lateral and posterior hypothalamus in the adult rat brain. When administered centrally to rats, these peptides stimulate food consumption. prepro-orexin mRNA level is up-regulated upon fasting, suggesting a physiological role for the peptides as mediators in the central feedback mechanism that regulates feeding behavior.
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            The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity.

            We describe a hypothalamus-specific mRNA that encodes preprohypocretin, the putative precursor of a pair of peptides that share substantial amino acid identities with the gut hormone secretin. The hypocretin (Hcrt) protein products are restricted to neuronal cell bodies of the dorsal and lateral hypothalamic areas. The fibers of these neurons are widespread throughout the posterior hypothalamus and project to multiple targets in other areas, including brainstem and thalamus. Hcrt immunoreactivity is associated with large granular vesicles at synapses. One of the Hcrt peptides was excitatory when applied to cultured, synaptically coupled hypothalamic neurons, but not hippocampal neurons. These observations suggest that the hypocretins function within the CNS as neurotransmitters.
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              The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness.

              Sleep and wakefulness are regulated to occur at appropriate times that are in accordance with our internal and external environments. Avoiding danger and finding food, which are life-essential activities that are regulated by emotion, reward and energy balance, require vigilance and therefore, by definition, wakefulness. The orexin (hypocretin) system regulates sleep and wakefulness through interactions with systems that regulate emotion, reward and energy homeostasis.
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                Author and article information

                Contributors
                +49-211-8112687 , +49-211-8114231 , haas@uni-duesseldorf.de
                Journal
                Cell Mol Life Sci
                Cellular and Molecular Life Sciences
                SP Birkhäuser Verlag Basel (Basel )
                1420-682X
                1420-9071
                13 February 2011
                13 February 2011
                August 2011
                : 68
                : 15
                : 2499-2512
                Affiliations
                [1 ]INSERM-U628, Integrative Physiology of Brain Arousal Systems, Claude Bernard University, 69373 Lyon, France
                [2 ]Department of Neurophysiology, Heinrich-Heine-University Düsseldorf, POB 101007, 40001 Düsseldorf, Germany
                Article
                631
                10.1007/s00018-011-0631-8
                3134769
                21318261
                d01eab96-2c09-4089-a484-ff8a73e4778b
                © The Author(s) 2011
                History
                : 21 November 2010
                : 25 December 2010
                : 13 January 2011
                Categories
                Review
                Custom metadata
                © Springer Basel AG 2011

                Molecular biology
                wake,histamine,orexin,sleep,cortical activation
                Molecular biology
                wake, histamine, orexin, sleep, cortical activation

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