title: Descending projections from the basal forebrain to the orexin neurons in mice.
abstract: The orexin (hypocretin) neurons play an essential role in promoting arousal, and loss of the orexin neurons results in narcolepsy, a condition characterized by chronic sleepiness and cataplexy. The orexin neurons excite wake-promoting neurons in the basal forebrain (BF), and a reciprocal projection from the BF back to the orexin neurons may help promote arousal and motivation. The BF contains at least three different cell types (cholinergic, glutamatergic, and γ-aminobutyric acid (GABA)ergic neurons) across its different regions (medial septum, diagonal band, magnocellular preoptic area, and substantia innominata). Given the neurochemical and anatomical heterogeneity of the BF, we mapped the pattern of BF projections to the orexin neurons across multiple BF regions and neuronal types. We performed conditional anterograde tracing using mice that express Cre recombinase only in neurons producing acetylcholine, glutamate, or GABA. We found that the orexin neurons are heavily apposed by axon terminals of glutamatergic and GABAergic neurons of the substantia innominata (SI) and magnocellular preoptic area, but there was no innervation by the cholinergic neurons. Channelrhodopsin-assisted circuit mapping (CRACM) demonstrated that glutamatergic SI neurons frequently form functional synapses with the orexin neurons, but, surprisingly, functional synapses from SI GABAergic neurons were rare. Considering their strong reciprocal connections, BF and orexin neurons likely work in concert to promote arousal, motivation, and other behaviors. J. Comp. Neurol. 525:1668-1684, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Lindsay J
authors.initials: LJ
authors.lastname: Agostinelli
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Loris L
authors.initials: LL
authors.lastname: Ferrari
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Mahoney
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Mochizuki
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Bradford B
authors.initials: BB
authors.lastname: Lowell
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Elda
authors.initials: E
authors.lastname: Arrigoni
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Scammell
mesh_terms: D000818:Animals; D066187:Basal Forebrain / Q000166:cytology* / Q000378:metabolism; D005260:Female; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D051379:Mice; D018613:Microscopy, Confocal; D009434:Neural Pathways / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D000068797:Orexins / Q000378:metabolism
chemical_list: D000068797:Orexins
keywords: CRACM; RRID: AB_10013483; RRID: AB_11180610; RRID: AB_262156; RRID: AB_653610; anterograde; hypocretin; lateral hypothalamus; magnocellular preoptic; mice; substantia innominata