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Nature. 2017 Aug 31;548(7669):582-587. doi: 10.1038/nature23663. Epub 2017 Aug 23.

Lhx6-positive GABA-releasing neurons of the zona incerta promote sleep.

Author information

1
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
2
Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
3
The Francis Crick Institute, London, UK.
4
Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA.
5
The McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
6
National Institute of Mental Health, Bethesda, Maryland, USA.

Abstract

Multiple populations of wake-promoting neurons have been characterized in mammals, but few sleep-promoting neurons have been identified. Wake-promoting cell types include hypocretin and GABA (γ-aminobutyric-acid)-releasing neurons of the lateral hypothalamus, which promote the transition to wakefulness from non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Here we show that a subset of GABAergic neurons in the mouse ventral zona incerta, which express the LIM homeodomain factor Lhx6 and are activated by sleep pressure, both directly inhibit wake-active hypocretin and GABAergic cells in the lateral hypothalamus and receive inputs from multiple sleep-wake-regulating neurons. Conditional deletion of Lhx6 from the developing diencephalon leads to decreases in both NREM and REM sleep. Furthermore, selective activation and inhibition of Lhx6-positive neurons in the ventral zona incerta bidirectionally regulate sleep time in adult mice, in part through hypocretin-dependent mechanisms. These studies identify a GABAergic subpopulation of neurons in the ventral zona incerta that promote sleep.

PMID:
28847002
PMCID:
PMC5958617
DOI:
10.1038/nature23663
[Indexed for MEDLINE]
Free PMC Article

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