Optogenetic identification of a rapid eye movement sleep modulatory circuit in the hypothalamus.
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.
Douglas Institute, Department of Psychiatry, McGill University, Montreal, Canada.
Sonia
S
Jego
Stephen D
SD
Glasgow
Carolina Gutierrez
CG
Herrera
Mats
M
Ekstrand
Sean J
SJ
Reed
Richard
R
Boyce
Jeffrey
J
Friedman
Denis
D
Burdakov
Antoine R
AR
Adamantidis
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D000075402:Channelrhodopsins; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation; D007028:Hypothalamic Hormones / Q000235:genetics; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008543:Melanins / Q000235:genetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D062308:Optogenetics; D010907:Pituitary Hormones / Q000235:genetics; D012895:Sleep, REM / Q000502:physiology*; D013826:Theta Rhythm / Q000187:drug effects / Q000235:genetics; D014161:Transduction, Genetic; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D000075402:Channelrhodopsins; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D007028:Hypothalamic Hormones; D008543:Melanins; D010907:Pituitary Hormones; C019463:melanin-concentrating hormone; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine; D001640:Bicuculline