title: Serotonin neurons in the dorsal raphe mediate the anticataplectic action of orexin neurons by reducing amygdala activity.
abstract: Narcolepsy is a sleep disorder caused by the loss of orexin (hypocretin)-producing neurons and marked by excessive daytime sleepiness and a sudden weakening of muscle tone, or cataplexy, often triggered by strong emotions. In a mouse model for narcolepsy, we previously demonstrated that serotonin neurons of the dorsal raphe nucleus (DRN) mediate the suppression of cataplexy-like episodes (CLEs) by orexin neurons. Using an optogenetic tool, in this paper we show that the acute activation of DRN serotonin neuron terminals in the amygdala, but not in nuclei involved in regulating rapid eye-movement sleep and atonia, suppressed CLEs. Not only did stimulating serotonin nerve terminals reduce amygdala activity, but the chemogenetic inhibition of the amygdala using designer receptors exclusively activated by designer drugs also drastically decreased CLEs, whereas chemogenetic activation increased them. Moreover, the optogenetic inhibition of serotonin nerve terminals in the amygdala blocked the anticataplectic effects of orexin signaling in DRN serotonin neurons. Taken together, the results suggest that DRN serotonin neurons, as a downstream target of orexin neurons, inhibit cataplexy by reducing the activity of amygdala as a center for emotional processing.
authors.affiliation: Department of Molecular Neuroscience and Integrative Physiology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Hasegawa
authors.affiliation: Department of Molecular Neuroscience and Integrative Physiology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Maejima
authors.affiliation: Department of Neuropharmacology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Department of General Zoology and Neurobiology, Ruhr-University Bochum, 44780 Bochum, Germany.
authors.forename: Olivia A
authors.identifier: 0000-0002-1541-2388
authors.initials: OA
authors.lastname: Masseck
authors.affiliation: Department of General Zoology and Neurobiology, Ruhr-University Bochum, 44780 Bochum, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Herlitze
authors.affiliation: Department of Neuropharmacology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshioka
authors.affiliation: Department of Molecular Neuroscience and Integrative Physiology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakurai
authors.affiliation: Department of Molecular Neuroscience and Integrative Physiology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8640, Japan; mieda@med.kanazawa-u.ac.jp.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Mieda
mesh_terms: D000679:Amygdala / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002375:Catalepsy / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D065847:Dorsal Raphe Nucleus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005133:Eye Movements; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D059326:Serotonergic Neurons / Q000378:metabolism* / Q000473:pathology; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D012701:Serotonin
keywords: amygdala; narcolepsy; orexin; serotonin; sleep