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      The sleep switch: hypothalamic control of sleep and wakefulness

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      Trends in Neurosciences

      Elsevier BV

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          Abstract

          More than 70 years ago, von Economo predicted a wake-promoting area in the posterior hypothalamus and a sleep-promoting region in the preoptic area. Recent studies have dramatically confirmed these predictions. The ventrolateral preoptic nucleus contains GABAergic and galaninergic neurons that are active during sleep and are necessary for normal sleep. The posterior lateral hypothalamus contains orexin/hypocretin neurons that are crucial for maintaining normal wakefulness. A model is proposed in which wake- and sleep-promoting neurons inhibit each other, which results in stable wakefulness and sleep. Disruption of wake- or sleep-promoting pathways results in behavioral state instability.

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          Most cited references 41

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          Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior

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            Thalamocortical oscillations in the sleeping and aroused brain.

            Sleep is characterized by synchronized events in billions of synaptically coupled neurons in thalamocortical systems. The activation of a series of neuromodulatory transmitter systems during awakening blocks low-frequency oscillations, induces fast rhythms, and allows the brain to recover full responsiveness. Analysis of cortical and thalamic networks at many levels, from molecules to single neurons to large neuronal assemblies, with a variety of techniques, ranging from intracellular recordings in vivo and in vitro to computer simulations, is beginning to yield insights into the mechanisms of the generation, modulation, and function of brain oscillations.
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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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                Author and article information

                Journal
                Trends in Neurosciences
                Trends in Neurosciences
                Elsevier BV
                01662236
                December 2001
                December 2001
                : 24
                : 12
                : 726-731
                Article
                10.1016/S0166-2236(00)02002-6
                11718878
                © 2001

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