Cells of a common developmental origin regulate REM/non-REM sleep and wakefulness in mice.
Mammalian sleep comprises rapid eye movement (REM) sleep and non-REM (NREM) sleep. To functionally isolate from the complex mixture of neurons populating the brainstem pons those involved in switching between REM and NREM sleep, we chemogenetically manipulated neurons of a specific embryonic cell lineage in mice. We identified excitatory glutamatergic neurons that inhibit REM sleep and promote NREM sleep. These neurons shared a common developmental origin with neurons promoting wakefulness; both derived from a pool of proneural hindbrain cells expressing Atoh1 at embryonic day 10.5. We also identified inhibitory γ-aminobutyric acid-releasing neurons that act downstream to inhibit REM sleep. Artificial reduction or prolongation of REM sleep in turn affected slow-wave activity during subsequent NREM sleep, implicating REM sleep in the regulation of NREM sleep.
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai Tsukuba, Ibaraki 305-8575, Japan. Japan Science and Technology Agency (JST), PRESTO, 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan. hayashi.yu.fp@u.tsukuba.ac.jp sitohara@brain.riken.jp.
Yu
Y
Hayashi
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai Tsukuba, Ibaraki 305-8575, Japan.
Mitsuaki
M
Kashiwagi
Laboratory for Behavioral Genetics, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan.
Kosuke
K
Yasuda
Laboratory for Behavioral Genetics, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan.
Reiko
R
Ando
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai Tsukuba, Ibaraki 305-8575, Japan.
Mika
M
Kanuka
Integrative Physiology of the Brain Arousal System, Lyon Neuroscience Research Center, INSERM U1028-CNRS UMR5292, School of Medicine, Claude Bernard University Lyon 1, F-69373 Lyon, France.
Kazuya
K
Sakai
Laboratory for Behavioral Genetics, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan. hayashi.yu.fp@u.tsukuba.ac.jp sitohara@brain.riken.jp.
Shigeyoshi
S
Itohara
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001933:Brain Stem / Q000166:cytology / Q000502:physiology; D019070:Cell Lineage; D002469:Cell Separation; D005260:Female; D005971:Glutamates / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D011149:Pons / Q000166:cytology / Q000502:physiology; D012249:Rhombencephalon / Q000166:cytology* / Q000196:embryology*; D012895:Sleep, REM / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology*; D005680:gamma-Aminobutyric Acid
D051792:Basic Helix-Loop-Helix Proteins; D005971:Glutamates; D005680:gamma-Aminobutyric Acid; C500943:Atoh1 protein, mouse