title: A role for orexin in central vestibular motor control.
abstract: The absence of orexin results in narcolepsy-cataplexy. While the function of the central orexinergic system in sleep regulation has been well studied, the role of orexin in motor control is largely unknown. Here, we show that orexin-A acts via OX(1) and OX(2) receptors to directly depolarize neurons in the rat lateral vestibular nucleus (LVN), a subcortical motor center, and enhance their sensitivity. A dual ionic mechanism involving both Na+-Ca²+ exchangers and inward rectifier K+ channels underlies these effects. Furthermore, orexin-A regulates central vestibular-mediated posture, motor balance and negative geotaxis. Orexin is critical when an animal is facing a major motor challenge as opposed to during rest and general movements. Therefore, orexin participates not only in sleep and emotion (nonsomatic) but also in motor (somatic) regulation, suggesting that the central orexinergic system plays an important role in somatic-nonsomatic integration. These findings may account for why the absence of orexin results in narcolepsy-cataplexy.
authors.affiliation: Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Mailbox 426, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.forename: Ye-Cheng
authors.initials: YC
authors.lastname: He
authors.forename: Hong-Zhao
authors.initials: HZ
authors.lastname: Li
authors.forename: Jing-Ning
authors.initials: JN
authors.lastname: Zhu
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D001583:Benzoxazoles / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D005106:Exploratory Behavior / Q000187:drug effects; D019417:Hindlimb Suspension / Q000379:methods; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008845:Microinjections / Q000379:methods; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009287:Naphthyridines; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D000068797:Orexins; D018408:Patch-Clamp Techniques; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D018013:Receptors, Neuropeptide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology; D003689:Vestibular Nucleus, Lateral / Q000166:cytology* / Q000378:metabolism*
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D001583:Benzoxazoles; D047908:Intracellular Signaling Peptides and Proteins; D009287:Naphthyridines; D009479:Neuropeptides; D000068797:Orexins; D018013:Receptors, Neuropeptide; D019831:Sodium-Calcium Exchanger; D014508:Urea; D013890:Thiourea