title: Control of REM sleep by ventral medulla GABAergic neurons.
abstract: Rapid eye movement (REM) sleep is a distinct brain state characterized by activated electroencephalogram and complete skeletal muscle paralysis, and is associated with vivid dreams. Transection studies by Jouvet first demonstrated that the brainstem is both necessary and sufficient for REM sleep generation, and the neural circuits in the pons have since been studied extensively. The medulla also contains neurons that are active during REM sleep, but whether they play a causal role in REM sleep generation remains unclear. Here we show that a GABAergic (γ-aminobutyric-acid-releasing) pathway originating from the ventral medulla powerfully promotes REM sleep in mice. Optogenetic activation of ventral medulla GABAergic neurons rapidly and reliably initiated REM sleep episodes and prolonged their durations, whereas inactivating these neurons had the opposite effects. Optrode recordings from channelrhodopsin-2-tagged ventral medulla GABAergic neurons showed that they were most active during REM sleep (REMmax), and during wakefulness they were preferentially active during eating and grooming. Furthermore, dual retrograde tracing showed that the rostral projections to the pons and midbrain and caudal projections to the spinal cord originate from separate ventral medulla neuron populations. Activating the rostral GABAergic projections was sufficient for both the induction and maintenance of REM sleep, which are probably mediated in part by inhibition of REM-suppressing GABAergic neurons in the ventrolateral periaqueductal grey. These results identify a key component of the pontomedullary network controlling REM sleep. The capability to induce REM sleep on command may offer a powerful tool for investigating its functions.
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA.
authors.forename: Franz
authors.initials: F
authors.lastname: Weber
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA.
authors.forename: Shinjae
authors.initials: S
authors.lastname: Chung
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Beier
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.
authors.forename: Liqun
authors.initials: L
authors.lastname: Luo
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Dan
mesh_terms: D000818:Animals; D004435:Eating / Q000502:physiology; D005260:Female; D059330:GABAergic Neurons / Q000502:physiology*; D006120:Grooming / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D009434:Neural Pathways / Q000502:physiology; D062308:Optogenetics; D010487:Periaqueductal Gray / Q000166:cytology / Q000502:physiology; D011149:Pons / Q000166:cytology / Q000502:physiology; D012895:Sleep, REM / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology; D013997:Time Factors; D014851:Wakefulness / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid