title: A Novel Population of Wake-Promoting GABAergic Neurons in the Ventral Lateral Hypothalamus.
abstract: The largest synaptic input to the sleep-promoting ventrolateral preoptic area (VLPO) [1] arises from the lateral hypothalamus [2], a brain area associated with arousal [3-5]. However, the neurochemical identity of the majority of these VLPO-projecting neurons within the lateral hypothalamus (LH), as well as their function in the arousal network, remains unknown. Herein we describe a population of VLPO-projecting neurons in the LH that express the vesicular GABA transporter (VGAT; a marker for GABA-releasing neurons). In addition to the VLPO, these neurons also project to several other established sleep and arousal nodes, including the tuberomammillary nucleus, ventral periaqueductal gray, and locus coeruleus. Selective and acute chemogenetic activation of LH VGAT(+) neurons was profoundly wake promoting, whereas acute inhibition increased sleep. Because of its direct and massive inputs to the VLPO, this population may play a particularly important role in sleep-wake switching.
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Venner
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Christelle
authors.initials: C
authors.lastname: Anaclet
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Rebecca Y
authors.initials: RY
authors.lastname: Broadhurst
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Clifford B
authors.initials: CB
authors.lastname: Saper
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA. Electronic address: pfuller@bidmc.harvard.edu.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Fuller
mesh_terms: D000818:Animals; D059330:GABAergic Neurons / Q000502:physiology*; D015870:Gene Expression; D007026:Hypothalamic Area, Lateral / Q000502:physiology*; D008297:Male; D051379:Mice; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics*; D014851:Wakefulness
chemical_list: D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse