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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Lineage
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GABAergic Neurons / drug effects
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GABAergic Neurons / metabolism*
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Gene Deletion
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Hippocampus / cytology
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Hippocampus / physiology
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LIM-Homeodomain Proteins / deficiency
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LIM-Homeodomain Proteins / drug effects
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LIM-Homeodomain Proteins / genetics
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LIM-Homeodomain Proteins / metabolism*
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Male
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Mice
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Nerve Tissue Proteins / deficiency
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Nerve Tissue Proteins / drug effects
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Orexins / metabolism
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Presynaptic Terminals / metabolism
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Sleep / drug effects
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Sleep / genetics
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Sleep / physiology*
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Sleep, REM / drug effects
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Sleep, REM / genetics
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Sleep, REM / physiology
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Time Factors
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Transcription Factors / deficiency
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Transcription Factors / drug effects
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Wakefulness / drug effects
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Wakefulness / genetics
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Wakefulness / physiology
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Zona Incerta / cytology*
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Zona Incerta / drug effects
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Zona Incerta / physiology
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gamma-Aminobutyric Acid / metabolism*
Substances
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LHX6 protein, mouse
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LIM-Homeodomain Proteins
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Nerve Tissue Proteins
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Orexins
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Transcription Factors
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gamma-Aminobutyric Acid