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Optogenetic identification of a rapid eye movement sleep modulatory circuit in the hypothalamus.


ABSTRACT: Rapid-eye movement (REM) sleep correlates with neuronal activity in the brainstem, basal forebrain and lateral hypothalamus. Lateral hypothalamus melanin-concentrating hormone (MCH)-expressing neurons are active during sleep, but their effects on REM sleep remain unclear. Using optogenetic tools in newly generated Tg(Pmch-cre) mice, we found that acute activation of MCH neurons (ChETA, SSFO) at the onset of REM sleep extended the duration of REM, but not non-REM, sleep episodes. In contrast, their acute silencing (eNpHR3.0, archaerhodopsin) reduced the frequency and amplitude of hippocampal theta rhythm without affecting REM sleep duration. In vitro activation of MCH neuron terminals induced GABAA-mediated inhibitory postsynaptic currents in wake-promoting histaminergic neurons of the tuberomammillary nucleus (TMN), and in vivo activation of MCH neuron terminals in TMN or medial septum also prolonged REM sleep episodes. Collectively, these results suggest that activation of MCH neurons maintains REM sleep, possibly through inhibition of arousal circuits in the mammalian brain.

SUBMITTER: Jego S 

PROVIDER: S-EPMC4974078 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Optogenetic identification of a rapid eye movement sleep modulatory circuit in the hypothalamus.

Jego Sonia S   Glasgow Stephen D SD   Herrera Carolina Gutierrez CG   Ekstrand Mats M   Reed Sean J SJ   Boyce Richard R   Friedman Jeffrey J   Burdakov Denis D   Adamantidis Antoine R AR  

Nature neuroscience 20130922 11


Rapid-eye movement (REM) sleep correlates with neuronal activity in the brainstem, basal forebrain and lateral hypothalamus. Lateral hypothalamus melanin-concentrating hormone (MCH)-expressing neurons are active during sleep, but their effects on REM sleep remain unclear. Using optogenetic tools in newly generated Tg(Pmch-cre) mice, we found that acute activation of MCH neurons (ChETA, SSFO) at the onset of REM sleep extended the duration of REM, but not non-REM, sleep episodes. In contrast, the  ...[more]

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