title: Inactivation of the Tuberomammillary Nucleus by GABAAReceptor Agonist Promotes Slow Wave Sleep in Freely Moving Rats and Histamine-Treated Rats.
abstract: A prominent hypothesis, the "flip-flop switch" model, predicts that histaminergic (HAergic) neurons in the tuberomammillary nucleus (TMN), an important component of the ascending arousal system, are inactivated by GABA mainly from the ventrolateral preoptic nucleus to allow the appearance and maintenance of sleep. However, which sleep state and the band of EEG activity induced by GABAergic inactivation of the TMN are unclear. In this study, alterations of sleep-wake states and cortical EEG power spectral density were investigated following muscimol, a GABAA-receptor agonist, microinjected bilaterally into the TMN in freely moving rats and HA pretreated rats, respectively. Muscimol dosed at 0.25 and 0.50 μg/side into the TMN during dark period dose-dependently increased slow wave sleep (SWS) accompanied by an increase in cortical EEG delta (0.5-4 Hz) and spindle (8.2-12 Hz) activities. In the meanwhile, wakefulness and EEG beta (12.2-30 Hz) activity were decreased significantly, while paradoxical sleep and EEG theta (4.2-8 Hz) activity were not changed. The increase of muscimol-induced SWS was because of prolonged SWS bout duration and not to an increased bout number. Muscimol (0.50 μg/side) administration 2 h after HA (0.125 μg/side) treatment during light period reversed the HA-induced wakefulness and EEG beta 2 (20.2-30 Hz) activity into SWS and EEG delta activity. These results demonstrate that the GABAergic inactivation of the TMN in freely moving rats and HA-treated rats promotes SWS and slow activity of cortical EEG, suggesting that the potential function of the GABAAreceptor in the TMN is to dampen vigilant arousal.
authors.affiliation: Department of Neuroscience, Anatomy, Histology and Embryology, Key laboratory of preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 199 Donggang Xi Road, Lanzhou, 730000, People's Republic of China.
authors.forename: Jun-Fan
authors.initials: JF
authors.lastname: Xie
authors.affiliation: Department of Neuroscience, Anatomy, Histology and Embryology, Key laboratory of preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 199 Donggang Xi Road, Lanzhou, 730000, People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: Fan
authors.affiliation: Department of Neuroscience, Anatomy, Histology and Embryology, Key laboratory of preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 199 Donggang Xi Road, Lanzhou, 730000, People's Republic of China.
authors.forename: Can
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neuroscience, Anatomy, Histology and Embryology, Key laboratory of preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 199 Donggang Xi Road, Lanzhou, 730000, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
authors.affiliation: Department of Neuroscience, Anatomy, Histology and Embryology, Key laboratory of preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 199 Donggang Xi Road, Lanzhou, 730000, People's Republic of China.|Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Gansu University of Chinese Medicine, 35 Dingxi Dong Road, Lanzhou, 730000, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Hou
authors.affiliation: Department of Neuroscience, Anatomy, Histology and Embryology, Key laboratory of preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 199 Donggang Xi Road, Lanzhou, 730000, People's Republic of China.
authors.forename: Le
authors.initials: L
authors.lastname: Xin
authors.affiliation: Department of Neuroscience, Anatomy, Histology and Embryology, Key laboratory of preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 199 Donggang Xi Road, Lanzhou, 730000, People's Republic of China.
authors.forename: Guang-Fu
authors.initials: GF
authors.lastname: Cui
authors.affiliation: Department of Neuroscience, Anatomy, Histology and Embryology, Key laboratory of preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 199 Donggang Xi Road, Lanzhou, 730000, People's Republic of China.
authors.forename: Lin-Xin
authors.initials: LX
authors.lastname: Wang
authors.affiliation: Department of Neuroscience, Anatomy, Histology and Embryology, Key laboratory of preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 199 Donggang Xi Road, Lanzhou, 730000, People's Republic of China. shaoyf@lzu.edu.cn.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Shao
authors.affiliation: Department of Neuroscience, Anatomy, Histology and Embryology, Key laboratory of preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 199 Donggang Xi Road, Lanzhou, 730000, People's Republic of China. houyiping@lzu.edu.cn.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Hou
mesh_terms: D000818:Animals; D004569:Electroencephalography / Q000187:drug effects / Q000379:methods; D058785:GABA-A Receptor Agonists / Q000008:administration & dosage*; D006632:Histamine / Q000008:administration & dosage*; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D009118:Muscimol / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology*; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*
chemical_list: D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D009118:Muscimol; D006632:Histamine
keywords: EEG power spectral density; GABA; Histamine; Sleep-wake states; Tuberomammillary nucleus