title: Ventral medullary control of rapid eye movement sleep and atonia.
abstract: Discrete populations of neurons at multiple levels of the brainstem control rapid eye movement (REM) sleep and the accompanying loss of postural muscle tone, or atonia. The specific contributions of these brainstem cell populations to REM sleep control remains incompletely understood. Here we show in rats that viral vector-based lesions of the ventromedial medulla at a level rostral to the inferior olive (pSOM) produced violent myoclonic twitches and abnormal electromyographic spikes, but not complete loss of tonic atonia, during REM sleep. Motor tone during non-REM (NREM) sleep was unaffected in these same animals. Acute chemogenetic activation of pSOM neurons in rats robustly and selectively suppressed REM sleep but not NREM sleep. Similar lesions targeting the more rostral ventromedial medulla (RVM) did not affect sleep or atonia, while chemogenetic stimulation of the RVM produced wakefulness and reduced sleep. Finally, selective activation of vesicular GABA transporter (VGAT) pSOM neurons in mice produced complete suppression of REM sleep whereas their loss increased EMG spikes during REM sleep. These results reveal a key contribution of the pSOM and specifically the VGAT+ neurons in this region in REM sleep and motor control.
authors.affiliation: Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Neurology, Division of Sleep Medicine, Boston, MA 02115, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Chen
authors.affiliation: Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Neurology, Division of Sleep Medicine, Boston, MA 02115, USA.
authors.forename: Ramalingam
authors.initials: R
authors.lastname: Vetrivelan
authors.affiliation: Department of Neurology, Shanghai First People's Hospital Shanghai Jiaotong University, Shanghai, China.
authors.forename: Chun-Ni
authors.initials: CN
authors.lastname: Guo
authors.affiliation: Advanced Magnetic Resonance Imaging Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Catie
authors.initials: C
authors.lastname: Chang
authors.affiliation: Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Neurology, Division of Sleep Medicine, Boston, MA 02115, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Fuller
authors.affiliation: Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Neurology, Division of Sleep Medicine, Boston, MA 02115, USA. Electronic address: jlu@bidmc.harvard.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004569:Electroencephalography; D004576:Electromyography; D007150:Immunohistochemistry; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D051379:Mice; D009207:Myoclonus / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012895:Sleep, REM / Q000502:physiology*; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics / Q000378:metabolism; D014851:Wakefulness / Q000187:drug effects
chemical_list: D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse
keywords: AAV; DREADD; GABA; REM arousal; VGAT