Journal Article

The rostromedial tegmental nucleus is essential for non-rapid eye movement sleep

Wang, Chen-Yao, Qu, Wei-Min, Yuan, Xiang-Shan, Zhao, Ya-Nan, Yang, Su-Rong, Wang, Dian-Ru, Cherasse, Yoan, Huang, Zhi-Li, Hu, Zhen-Zhen, Ye, Chen-Bo, Guo, Wei, Luo, Yan-Jia, Yan, Yu-Dong, Ding, Yu-Qiang, Lazarus, Michael, Sun, Huan-Xin, Yin, Dou

2018

Overview

The rostromedial tegmental nucleus (RMTg), also called the GABAergic tail of the ventral tegmental area, projects to the midbrain dopaminergic system, dorsal raphe nucleus, locus coeruleus, and other regions. Whether the RMTg is involved in sleep-wake regulation is unknown. In the present study, pharmacogenetic activation of rat RMTg neurons promoted non-rapid eye movement (NREM) sleep with increased slow-wave activity (SWA). Conversely, rats after neurotoxic lesions of 8 or 16 days showed decreased NREM sleep with reduced SWA at lights on. The reduced SWA persisted at least 25 days after lesions. Similarly, pharmacological and pharmacogenetic inactivation of rat RMTg neurons decreased NREM sleep. Electrophysiological experiments combined with optogenetics showed a direct inhibitory connection between the terminals of RMTg neurons and midbrain dopaminergic neurons. The bidirectional effects of the RMTg on the sleep-wake cycle were mimicked by the modulation of ventral tegmental area (VTA)/substantia nigra compacta (SNc) dopaminergic neuronal activity using a pharmacogenetic approach. Furthermore, during the 2-hour recovery period following 6-hour sleep deprivation, the amount of NREM sleep in both the lesion and control rats was significantly increased compared with baseline levels; however, only the control rats showed a significant increase in SWA compared with baseline levels. Collectively, our findings reveal an essential role of the RMTg in the promotion of NREM sleep and homeostatic regulation.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animals / Authorship / Biology and Life Sciences / Channelrhodopsins - genetics / Channelrhodopsins - metabolism / Clozapine - analogs & derivatives / Clozapine - pharmacology / Collaboration / Control / Deactivation / Diabetes / Dopamine / Dopamine - metabolism / Dopamine receptors / Dopaminergic Neurons - cytology / Dopaminergic Neurons - drug effects / Dopaminergic Neurons - physiology / Dorsal raphe nucleus / Dorsal Raphe Nucleus - anatomy & histology / Dorsal Raphe Nucleus - drug effects / Dorsal Raphe Nucleus - physiology / Dorsal tegmental nucleus / Electrodes, Implanted / Electroencephalography / Eye / Eye movements / Eye Movements - physiology / gamma-Aminobutyric Acid - metabolism / Genes, Reporter / Genetics / Ibotenic Acid - toxicity / Inactivation / Information processing / Laboratories / Lesions / Locus coeruleus / Locus Coeruleus - anatomy & histology / Locus Coeruleus - drug effects / Locus Coeruleus - physiology / Luminescent Proteins - genetics / Luminescent Proteins - metabolism / Male / Medicine and Health Sciences / Mesencephalon / Mesencephalon - anatomy & histology / Mesencephalon - drug effects / Mesencephalon - physiology / Movements / Neural circuitry / Neural Pathways - anatomy & histology / Neural Pathways - drug effects / Neural Pathways - physiology / Neurobiology / Neurons / Neurosciences / Neurotoxicity / NREM sleep / Optics / Optogenetics / Pars Compacta - anatomy & histology / Pars Compacta - drug effects / Pars Compacta - physiology / Pharmacology / Physiological aspects / Raphe nuclei / Rapid eye movement state / Rats / Rats, Sprague-Dawley / Receptors, Muscarinic - genetics / Receptors, Muscarinic - metabolism / Red Fluorescent Protein / REM sleep / Research and Analysis Methods / Rodents / Sleep / Sleep (NREM) / Sleep (REM) / Sleep - physiology / Sleep and wakefulness / Sleep deprivation / Sleep Deprivation - physiopathology / Stereotaxic Techniques / Substantia nigra / Tegmental nucleus / Ventral Tegmental Area - anatomy & histology / Ventral Tegmental Area - drug effects / Ventral Tegmental Area - physiology / Ventral tegmentum / Wakefulness - physiology / γ-Aminobutyric acid