Orexin

Orexin neurons receive a variety of signals related to environmental, physiological orexin emotional stimuli, and project broadly to the entire CNS.

Federal government websites often end in. The site is secure. Preview improvements coming to the PMC website in October Learn More or Try it out now. The hypothalamus monitors body homeostasis and regulates various behaviors such as feeding, thermogenesis, and sleeping.

Orexin

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Humans and animals lacking orexin neurons exhibit daytime sleepiness, sleep attacks, and state instability. While the circuit basis by which orexin neurons contribute to consolidated wakefulness remains unclear, existing models posit that orexin neurons provide their wake-stabilizing influence by exerting excitatory tone on other brain arousal nodes. Here we show using in vivo optogenetics, in vitro optogenetic-based circuit mapping, and single-cell transcriptomics that orexin neurons also contribute to arousal maintenance through indirect inhibition of sleep-promoting neurons of the ventrolateral preoptic nucleus. Activation of this subcortical circuit rapidly drives wakefulness from sleep by differentially modulating the activity of ventrolateral preoptic neurons. We further identify and characterize a feedforward circuit through which orexin and co-released glutamate acts to indirectly target and inhibit sleep-promoting ventrolateral preoptic neurons to produce arousal. This revealed circuitry provides an alternate framework for understanding how orexin neurons contribute to the maintenance of consolidated wakefulness and stabilize behavioral state. Uma R. Mohan, Honghui Zhang, … Joshua Jacobs. Matthias Ollivier, Joselyn S. Soto, … Baljit S. Orexin Ox; also called hypocretin neurons in the lateral hypothalamus play an indispensable role in stabilizing and maintaining wakefulness.

Values are normalized to the mean Gapdh.

Orexins, also known as hypocretins, are two neuropeptides secreted from orexin-containing neurons, mainly in the lateral hypothalamus LH. The orexins, also known as hypocretins, are a pair of neuropeptides that are mainly derived from orexin-containing neurons in the lateral hypothalamus LH. Orexin-A OA; hypocretin-1 and orexin-B OB; hypocretin-2 are closely related small peptides that are widely distributed throughout the central and peripheral nervous systems de Lecea et al. Orexins stimulate food intake upon intracerebroventricular administration, and were originally described as regulators of feeding behavior Yamanaka et al. Subsequent experiments revealed many other important physiological functions of these peptides, including regulation of the sleep—wake cycle de Lecea and Sutcliffe, ; Chow and Cao, , energy homeostasis Tsuneki et al. Orexins bind their cognate G-protein—coupled receptors GPCRs , orexin receptor type 1 OX1R, also named as Hcrtr-1 and type 2 OX2R, or Hcrtr-2 , which activate different downstream signal pathways, thereby exerting a variety of physiological functions Sakurai et al. Orexin and orexin receptors are ectopically expressed in many diseases Perez et al.

Federal government websites often end in. The site is secure. Preview improvements coming to the PMC website in October Learn More or Try it out now. Orexins, also known as hypocretins, are two neuropeptides secreted from orexin-containing neurons, mainly in the lateral hypothalamus LH.

Orexin

The most common form of narcolepsy , type 1, in which the individual experiences brief losses of muscle tone "drop attacks" or cataplexy , is caused by a lack of orexin in the brain due to destruction of the cells that produce it. There are 50,—80, orexin-producing neurons in the human brain, [8] located predominantly in the perifornical area and lateral hypothalamus. Orexin was discovered in almost simultaneously by two independent groups of researchers working on the rat brain. Luis de Lecea, Thomas Kilduff , and colleagues reported the discovery of the hypocretin system at the same time as Takeshi Sakurai from Masashi Yanagisawa 's lab at the University of Texas Southwestern Medical Center at Dallas reported the discovery of the orexins to reflect the orexigenic appetite-stimulating activity of these peptides. In their paper describing these neuropeptides, they also reported discovery of two orexin receptors, dubbed OX 1 R and OX 2 R. The two groups also took different approaches towards their discovery.

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Relative gene expression between samples was calculated using the 2 -Ct method 53 , In accordance with these findings, intraperitoneal administration of OX1R or OX2R antagonist decreases ethanol intake and ethanol self-administration. OX1R mainly activates the G q subtype, which subsequently induces a downstream cascade response. Search Search articles by subject, keyword or author. Orexin neurons are indispensable for stress-induced thermogenesis in mice. Chow, M. Neuronal dynamics direct cerebrospinal fluid perfusion and brain clearance Article 28 February Consistent with this, disruption of the system causes narcoleptic symptoms in animal models. Ac, anterior commissure; 3V, 3 rd ventricle; Opt, optical chiasm. Glossary Cataplexy A sudden weakening of muscle tone that often accompanies narcolepsy.

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Promotion of wakefulness and energy expenditure by Orexin-A in the ventrolateral preoptic area. Nicotine self-administration in the rat: effects of hypocretin antagonists and changes in hypocretin mRNA. Venner, A. Orexin neurons receive a variety of signals related to environmental, physiological and emotional stimuli, and project broadly to the entire CNS. Exercise increases the level of plasma orexin A in humans. A better understanding of the synaptic, cellular, and circuit bases by which Ox neurons stabilize and maintain wakefulness has important implications for treating patients with neurological disorders associated with arousal dysfunction. Orexin neurons promote wakefulness through monoaminergic nuclei that are wake-active. Relative gene expression between samples was calculated using the 2 -Ct method 53 , The novel brain neuropeptide, orexin-A, modulates the sleep-wake cycle of rats. Feng, P. The orexin system was initially suggested to be primarily involved in the stimulation of food intake, based on the finding that central administration of orexin-A and -B increased food intake. We purchased all the custom primers from Sigma-Aldrich, St. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Sleep 11 , 1—16 Orexins are essential in reward seeking: they do not influence the primary reinforcing or priming effects of rewards, but they support motivated behaviour.