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Pontine control of rapid eye movement sleep and fear memory

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机构： [1]Ningxia Key Laboratory of Craniocerebral Diseases, Department of Anatomy, Histology and Embryology, School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia, China. [2]Stroke Center, Department of Neurology, 1st Hospital of Jilin University, Changchun, China. [3]Shanghai Yueyang Integrated Medicine Hospital, Shanghai, China. [4]Department of Neurology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China. [5]Department of Neurobiology, School of Basic Medical Science, Shanghai Medical College, Fudan University, Shanghai, China. [6]Department of Anatomy, Physiology & Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA. [7]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China. [8]Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong, China. [9]Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi, USA. [10]Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.

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关键词： fear memory glutamate hippocampus medial septum neural circuit REM sleep SLD

摘要：

We often experience dreams of strong irrational and negative emotional contents with postural muscle paralysis during rapid eye movement (REM) sleep, but how REM sleep is generated and its function remain unclear. In this study, we investigate whether the dorsal pontine sub-laterodorsal tegmental nucleus (SLD) is necessary and sufficient for REM sleep and whether REM sleep elimination alters fear memory.To investigate whether activation of SLD neurons is sufficient for REM sleep induction, we expressed channelrhodopsin-2 (ChR2) in SLD neurons by bilaterally injecting AAV1-hSyn-ChR2-YFP in rats. We next selectively ablated either glutamatergic or GABAergic neurons from the SLD in mice in order to identify the neuronal subset crucial for REM sleep. We finally investigated the role of REM sleep in consolidation of fear memory using rat model with complete SLD lesions.We demonstrate the sufficiency of the SLD for REM sleep by showing that photo-activation of ChR2 transfected SLD neurons selectively promotes transitions from non-REM (NREM) sleep to REM sleep in rats. Diphtheria toxin-A (DTA) induced lesions of the SLD in rats or specific deletion of SLD glutamatergic neurons but not GABAergic neurons in mice completely abolish REM sleep, demonstrating the necessity of SLD glutamatergic neurons for REM sleep. We then show that REM sleep elimination by SLD lesions in rats significantly enhances contextual and cued fear memory consolidation by 2.5 and 1.0 folds, respectively, for at least 9 months. Conversely, fear conditioning and fear memory trigger doubled amounts of REM sleep in the following night, and chemo-activation of SLD neurons projecting to the medial septum (MS) selectively enhances hippocampal theta activity in REM sleep; this stimulation immediately after fear acquisition reduces contextual and cued fear memory consolidation by 60% and 30%, respectively.SLD glutamatergic neurons generate REM sleep and REM sleep and SLD via the hippocampus particularly down-regulate contextual fear memory.© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

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出版当年[2022]版：

大类 | 1 区

医学

小类 | 1 区药学 1 区神经科学

最新[2023]版：

大类 | 1 区医学

小类 | 2 区神经科学 2 区药学

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出版当年[2021]版：

Q1 NEUROSCIENCES Q1 PHARMACOLOGY & PHARMACY

最新[2023]版：

Q1 PHARMACOLOGY & PHARMACY Q1 NEUROSCIENCES

影响因子： 4.8 最新[2023版] 5.9 最新五年平均 7.035 出版当年[2021版] 6.329 出版当年五年平均 5.243 出版前一年[2020版] 5.5 出版后一年[2022版]

第一作者：

第一作者机构： [1]Ningxia Key Laboratory of Craniocerebral Diseases, Department of Anatomy, Histology and Embryology, School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia, China. [2]Stroke Center, Department of Neurology, 1st Hospital of Jilin University, Changchun, China.

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通讯作者：

通讯机构： [2]Stroke Center, Department of Neurology, 1st Hospital of Jilin University, Changchun, China. [10]Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA. [*1]Department of Neurology, 1st Hospital of Jilin University.Changchun, Jilin, China.

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Pontine control of rapid eye movement sleep and fear memory

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