Galanin neurons in the ventrolateral preoptic area promote sleep and heat loss in mice.

The preoptic area (POA) is necessary for sleep, but the fundamental POA circuits have remained elusive. Previous studies showed that galanin (GAL)- and GABA-producing neurons in the ventrolateral preoptic nucleus (VLPO) express cFos after periods of increased sleep and innervate key wake-promoting regions. Although lesions in this region can produce insomnia, high frequency photostimulation of the POA neurons was shown to paradoxically cause waking, not sleep. Here we report that photostimulation of VLPO neurons in mice promotes sleep with low frequency stimulation (1-4 Hz), but causes conduction block and waking at frequencies above 8 Hz. Further, optogenetic inhibition reduces sleep. Chemogenetic activation of VLPO neurons confirms the increase in sleep, and also reduces body temperature. In addition, chemogenetic activation of VLPO neurons induces short-latency sleep in an animal model of insomnia. Collectively, these findings establish a causal role of VLPO neurons in both sleep induction and heat loss.