title: Ca(2+) in the dorsal raphe nucleus promotes wakefulness via endogenous sleep-wake regulating pathway in the rats.
abstract: Serotonergic neurons in the dorsal raphe nucleus (DRN) are involved in the control of sleep-wake states. Our previous studies have indicated that calcium (Ca(2+)) modulation in the DRN plays an important role in rapid-eye-movement sleep (REMS) and non-REMS (NREMS) regulation during pentobarbital hypnosis. The present study investigated the effects of Ca(2+) in the DRN on sleep-wake regulation and the related neuronal mechanism in freely moving rats. Our results showed that microinjection of CaCl2 (25 or 50 nmol) in the DRN promoted wakefulness and suppressed NREMS including slow wave sleep and REMS in freely moving rats. Application of CaCl2 (25 or 50 nmol) in the DRN significantly increased serotonin in the DRN and hypothalamus, and noradrenaline in the locus coeruleus and hypothalamus. Immunohistochemistry study indicated that application of CaCl2 (25 or 50 nmol) in the DRN significantly increased c-Fos expression ratio in wake-promoting neurons including serotonergic neurons in the DRN, noradrenergic neurons in the locus coeruleus, and orxinergic neurons in the perifornical nucleus, but decreased c-Fos expression ratio of GABAergic sleep-promoting neurons in the ventrolateral preoptic nucleus. These results suggest that Ca(2+) in the DRN exert arousal effects via up-regulating serotonergic functions in the endogenous sleep-wake regulating pathways.
authors.affiliation: Department of pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Cui
authors.affiliation: Department of pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Sheng-Jie
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Department of pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Cui
authors.affiliation: Department of pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Xue-Qiong
authors.initials: XQ
authors.lastname: Zhang
authors.affiliation: Department of pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Yuan-Li
authors.initials: YL
authors.lastname: Huang
authors.affiliation: Department of pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Department of pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Xu
authors.affiliation: Department of pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ding
authors.affiliation: Department of pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Jin-Zhi
authors.initials: JZ
authors.lastname: Song
authors.affiliation: Department of pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ye
authors.affiliation: Department of pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Zhao-Fu
authors.initials: ZF
authors.lastname: Sheng
authors.affiliation: Department of pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Zi-Jun
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Department of pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Road, Beijing, 100191, China. zhyh@hsc.pku.edu.cn.
authors.forename: Yong-He
authors.initials: YH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology*; D065847:Dorsal Raphe Nucleus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008845:Microinjections; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D015306:Biogenic Monoamines; D018377:Neurotransmitter Agents; D002122:Calcium Chloride
keywords: Calcium; Dorsal raphe nucleus; Serotonin; Sleep