The wake-promoting hypocretin-orexin neurons are in an intrinsic state of membrane depolarization.

Wakefulness depends on the activity of hypocretin-orexin neurons because their lesion results in narcolepsy. How these neurons maintain their activity to promote wakefulness is not known. Here, by recording for the first time from hypocretin-orexin neurons and comparing their properties with those of neurons expressing melanin-concentrating hormone, we show that hypocretin-orexin neurons are in an intrinsic state of membrane depolarization that promotes their spontaneous activity. We propose that wakefulness and associated energy expenditure thus depend on that property, which allows the hypocretin-orexin neurons to maintain a tonic excitatory influence on the central arousal and peripheral sympathetic systems.