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  • Title: An Inhibitory Lateral Hypothalamic-Preoptic Circuit Mediates Rapid Arousals from Sleep.
    Author: Venner A, De Luca R, Sohn LT, Bandaru SS, Verstegen AMJ, Arrigoni E, Fuller PM.
    Journal: Curr Biol; 2019 Dec 16; 29(24):4155-4168.e5. PubMed ID: 31761703.
    Abstract:
    Among the neuronal populations implicated in sleep-wake control, the ventrolateral preoptic (VLPO) nucleus has emerged as a key sleep-promoting center. However, the synaptic drives that regulate the VLPO to control arousal levels in vivo have not to date been identified. Here, we show that sleep-promoting galaninergic neurons within the VLPO nucleus, defined pharmacologically and by single-cell transcript analysis, are postsynaptic targets of lateral hypothalamic GABAergic (LHGABA) neurons and that activation of this pathway in vivo rapidly drives wakefulness. Ca2+ imaging from LHGABA neurons indicate that they are both wake and rapid eye movement (REM)-sleep active. Consistent with the potent arousal-promoting property of the LHGABA → VLPO pathway, presynaptic inputs to LHGABA neurons originate from several canonical stress- and arousal-related network nodes. This work represents the first demonstration that direct synaptic inhibition of the VLPO area can suppress sleep-promoting neurons to rapidly promote arousal.
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