Lhx6-positive GABA-releasing neurons of the zona incerta promote sleep
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Kai Liu Juhyun Kim Dong Won Kim Yi Stephanie Zhang Hechen Bao Myrto Denaxa Szu-Aun Lim Eileen Kim Chang Liu Ian R Wickersham Vassilis Pachnis Samer Hattar Juan Song Solange P Brown Seth BlackshawAbstract
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.
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Journal Nature
Volume 548
Issue number 7669
Pages 582-587
Available online
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Publisher website (DOI) 10.1038/nature23663
Figshare View on figshare
Europe PubMed Central 28847002
Pubmed 28847002
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