title: Selectively driving cholinergic fibers optically in the thalamic reticular nucleus promotes sleep.
abstract: Cholinergic projections from the basal forebrain and brainstem are thought to play important roles in rapid eye movement (REM) sleep and arousal. Using transgenic mice in which channelrhdopsin-2 is selectively expressed in cholinergic neurons, we show that optical stimulation of cholinergic inputs to the thalamic reticular nucleus (TRN) activates local GABAergic neurons to promote sleep and protect non-rapid eye movement (NREM) sleep. It does not affect REM sleep. Instead, direct activation of cholinergic input to the TRN shortens the time to sleep onset and generates spindle oscillations that correlate with NREM sleep. It does so by evoking excitatory postsynaptic currents via α7-containing nicotinic acetylcholine receptors and inducing bursts of action potentials in local GABAergic neurons. These findings stand in sharp contrast to previous reports of cholinergic activity driving arousal. Our results provide new insight into the mechanisms controlling sleep.
authors.affiliation: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Kun-Ming
authors.initials: KM
authors.lastname: Ni
authors.affiliation: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.|Fuzhou Children's Hospital, Fujian, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Hou
authors.affiliation: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Ci-Hang
authors.initials: CH
authors.lastname: Yang
authors.affiliation: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Dong
authors.affiliation: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Neurobiology Section, Division of Biological Sciences, Center for Neural Circuits and Behavior, University of California, San Diego, La Jolla, United States.
authors.forename: Darwin K
authors.initials: DK
authors.lastname: Berg
authors.affiliation: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Shumin
authors.initials: S
authors.lastname: Duan
authors.affiliation: Department of Neurobiology, Institute of Neuroscience, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Collaborative Innovation Center for Brain Science, Zhejiang University School of Medicine, Hangzhou, China.|Soft Matter Research Center, Zhejiang University, Hangzhou, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Li
mesh_terms: D000818:Animals; D001143:Arousal; D002799:Cholinergic Fibers / Q000502:physiology*; D059330:GABAergic Neurons / Q000502:physiology*; D008822:Mice, Transgenic; D010775:Photic Stimulation; D012890:Sleep; D013787:Thalamic Nuclei / Q000502:physiology*
keywords: Cholinergic projections; GABAergic neurons; Optogenetics; Sleep; TRN; cell biology; mouse; neuroscience