title: Selective activation of cholinergic basal forebrain neurons induces immediate sleep-wake transitions.
abstract: The basal forebrain (BF) plays a crucial role in cortical activation [1, 2]. However, the exact role of cholinergic BF (ch-BF) neurons in the sleep-wake cycle remains unclear [3, 4]. We demonstrated that photostimulation of ch-BF neurons genetically targeted with channelrhodopsin 2 (ChR2) was sufficient to induce an immediate transition to waking or rapid eye movement (REM) sleep from slow-wave sleep (SWS). Light stimulation was most likely to induce behavioral arousal during SWS, but not during REM sleep, a result in contrast to the previously reported photostimulation of noradrenergic or hypocretin neurons that induces wake transitions from both SWS and REM sleep. Furthermore, the ratio of light-induced transitions from SWS to wakefulness or to REM sleep did not significantly differ from that of natural transitions, suggesting that activation of ch-BF neurons facilitates the transition from SWS but does not change the direction of the transition. Excitation of ch-BF neurons during wakefulness or REM sleep sustained the cortical activation. Stimulation of these neurons for 1 hr induced a delayed increase in the duration of wakefulness in the subsequent inactive period. Our results suggest that activation of ch-BF neurons alone is sufficient to suppress SWS and promote wakefulness and REM sleep.
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Yu-feng
authors.initials: YF
authors.lastname: Shi
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Xi
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Zhi-bing
authors.initials: ZB
authors.lastname: Tan
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Xiao-ming
authors.initials: XM
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Guoping
authors.initials: G
authors.lastname: Feng
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Minmin
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Zhi-li
authors.initials: ZL
authors.lastname: Huang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China. Electronic address: duanshumin@zju.edu.cn.
authors.forename: Shumin
authors.initials: S
authors.lastname: Duan
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China. Electronic address: yanqinyu@zju.edu.cn.
authors.forename: Yan-qin
authors.initials: YQ
authors.lastname: Yu
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000075402:Channelrhodopsins; D059329:Cholinergic Neurons / Q000502:physiology*; D004569:Electroencephalography; D004576:Electromyography; D008822:Mice, Transgenic; D010775:Photic Stimulation; D016548:Prosencephalon / Q000166:cytology / Q000502:physiology*; D012890:Sleep / Q000502:physiology*; D012895:Sleep, REM / Q000502:physiology; D014851:Wakefulness / Q000502:physiology*
chemical_list: D000075402:Channelrhodopsins