title: Role of the medial prefrontal cortex in cataplexy.
abstract: Narcolepsy is characterized by chronic sleepiness and cataplexy, episodes of profound muscle weakness that are often triggered by strong, positive emotions. Narcolepsy with cataplexy is caused by a loss of orexin (also known as hypocretin) signaling, but almost nothing is known about the neural mechanisms through which positive emotions trigger cataplexy. Using orexin knock-out mice as a model of narcolepsy, we found that palatable foods, especially chocolate, markedly increased cataplexy and activated neurons in the medial prefrontal cortex (mPFC). Reversible suppression of mPFC activity using an engineered chloride channel substantially reduced cataplexy induced by chocolate but did not affect spontaneous cataplexy. In addition, neurons in the mPFC innervated parts of the amygdala and lateral hypothalamus that contain neurons active during cataplexy and that innervate brainstem regions known to regulate motor tone. These observations indicate that the mPFC is a critical site through which positive emotions trigger cataplexy.
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Yo
authors.initials: Y
authors.lastname: Oishi
authors.forename: Rhiannan H
authors.initials: RH
authors.lastname: Williams
authors.forename: Lindsay
authors.initials: L
authors.lastname: Agostinelli
authors.forename: Elda
authors.initials: E
authors.lastname: Arrigoni
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Fuller
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Mochizuki
authors.forename: Clifford B
authors.initials: CB
authors.lastname: Saper
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Scammell
mesh_terms: D000818:Animals; D002099:Cacao; D002385:Cataplexy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D004569:Electroencephalography / Q000379:methods; D005247:Feeding Behavior / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009479:Neuropeptides / Q000172:deficiency / Q000235:genetics; D000068797:Orexins; D017397:Prefrontal Cortex / Q000502:physiology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins