title: Neurons containing orexin or melanin concentrating hormone reciprocally regulate wake and sleep.
abstract: Neurons containing orexin (hypocretin), or melanin concentrating hormone (MCH) are intermingled with each other in the perifornical and lateral hypothalamus. Each is a separate and distinct neuronal population, but they project to similar target areas in the brain. Orexin has been implicated in regulating arousal since loss of orexin neurons is associated with the sleep disorder narcolepsy. Microinjections of orexin into the brain or optogenetic stimulation of orexin neurons increase waking. Orexin neurons are active in waking and quiescent in sleep, which is consistent with their role in promoting waking. On the other hand, the MCH neurons are quiet in waking but active in sleep, suggesting that they could initiate sleep. Recently, for the first time the MCH neurons were stimulated optogenetically and it increased sleep. Indeed, optogenetic activation of MCH neurons induced sleep in both mice and rats at a circadian time when they should be awake, indicating the powerful effect that MCH neurons have in suppressing the wake-promoting effect of not only orexin but also of all of the other arousal neurotransmitters. Gamma-Aminobutyric acid (GABA) is coexpressed with MCH in the MCH neurons, although MCH is also inhibitory. The inhibitory tone of the MCH neurons is opposite to the excitatory tone of the orexin neurons. We hypothesize that strength in activity of each determines wake vs. sleep.
authors.affiliation: Departments of Psychiatry and Behavioral Sciences, Medical University of South Carolina Charleston, SC, USA.
authors.forename: Roda Rani
authors.initials: RR
authors.lastname: Konadhode
authors.affiliation: Departments of Psychiatry and Behavioral Sciences, Medical University of South Carolina Charleston, SC, USA.
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Pelluru
authors.affiliation: Departments of Psychiatry and Behavioral Sciences, Medical University of South Carolina Charleston, SC, USA ; Ralph H. Johnson VA Medical Center, Medical University of South Carolina Charleston, SC, USA.
authors.forename: Priyattam J
authors.initials: PJ
authors.lastname: Shiromani
keywords: hypothalamus; melanin concentrating hormone; optogenetics; sleep