title: The GABAergic parafacial zone is a medullary slow wave sleep-promoting center.
abstract: Work in animals and humans has suggested the existence of a slow wave sleep (SWS)-promoting/electroencephalogram (EEG)-synchronizing center in the mammalian lower brainstem. Although sleep-active GABAergic neurons in the medullary parafacial zone (PZ) are needed for normal SWS, it remains unclear whether these neurons can initiate and maintain SWS or EEG slow-wave activity (SWA) in behaving mice. We used genetically targeted activation and optogenetically based mapping to examine the downstream circuitry engaged by SWS-promoting PZ neurons, and we found that this circuit uniquely and potently initiated SWS and EEG SWA, regardless of the time of day. PZ neurons monosynaptically innervated and released synaptic GABA onto parabrachial neurons, which in turn projected to and released synaptic glutamate onto cortically projecting neurons of the magnocellular basal forebrain; thus, there is a circuit substrate through which GABAergic PZ neurons can potently trigger SWS and modulate the cortical EEG.
authors.affiliation: Department of Neurology, Division of Sleep Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Christelle
authors.initials: C
authors.lastname: Anaclet
authors.affiliation: Department of Neurology, Division of Sleep Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Loris
authors.initials: L
authors.lastname: Ferrari
authors.affiliation: Department of Neurology, Division of Sleep Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Elda
authors.initials: E
authors.lastname: Arrigoni
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA.
authors.forename: Caroline E
authors.identifier: 0000000258566387
authors.initials: CE
authors.lastname: Bass
authors.affiliation: Department of Neurology, Division of Sleep Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Clifford B
authors.initials: CB
authors.lastname: Saper
authors.affiliation: Department of Neurology, Division of Sleep Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Neurology, Division of Sleep Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Fuller
mesh_terms: D000818:Animals; D004569:Electroencephalography; D059330:GABAergic Neurons / Q000502:physiology*; D019426:Integrases / Q000235:genetics; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology*; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D065823:Parabrachial Nucleus / Q000166:cytology / Q000502:physiology; D016548:Prosencephalon / Q000166:cytology / Q000502:physiology; D012125:Respiratory Center / Q000166:cytology / Q000502:physiology*; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000503:physiopathology; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D005680:gamma-Aminobutyric Acid; C045073:Cre recombinase; D019426:Integrases