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

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 Blackshaw

Research output: Contribution to journalArticlepeer-review

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 ('3-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.

Original languageEnglish (US)
Pages (from-to)582-587
Number of pages6
JournalNature
Volume548
Issue number7669
DOIs
StatePublished - Aug 31 2017

ASJC Scopus subject areas

  • General

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