Circadian VIPergic Neurons of the Suprachiasmatic Nuclei Sculpt the Sleep-Wake Cycle

Although the mammalian rest-activity cycle is controlled by a “master clock” in the suprachiasmatic nucleus (SCN) of the hypothalamus, it is unclear how firing of individual SCN neurons gates individual features of daily activity. Here, we demonstrate that a specific transcriptomically identified population of mouse VIP+ SCN neurons is active at the “wrong” time of day—nighttime—when most SCN neurons are silent. Using chemogenetic and optogenetic strategies, we show that these neurons and their cellular clocks are necessary and sufficient to gate and time nighttime sleep but have no effect upon daytime sleep. We propose that mouse nighttime sleep, analogous to the human siesta, is a “hard-wired” property gated by specific neurons of the master clock to favor subsequent alertness prior to dawn (a circadian “wake maintenance zone”). Thus, the SCN is not simply a 24-h metronome: specific populations sculpt critical features of the sleep-wake cycle. •Specific VIP+ neurons of the SCN fire at night when most others are silent•Activating or silencing these VIP+ neurons controls nighttime but not daytime sleep•Circadian clockwork within these specific neurons times the daily “siesta”•The activity of these neurons, in turn, programs subsequent end-of-day alertness The “master” circadian clock generally indicates day and night by tonic daytime firing. A specific population of neurons, active when the rest of the SCN is silent, directs nighttime “siesta” sleep but not daytime sleep, thereby timing end-of-day alertness.