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 POAGAL neurons was shown to paradoxically cause waking, not sleep. Here we report that photostimulation of VLPOGAL 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 VLPOGAL neurons confirms the increase in sleep, and also reduces body temperature. In addition, chemogenetic activation of VLPOGAL neurons induces short-latency sleep in an animal model of insomnia. Collectively, these findings establish a causal role of VLPOGAL neurons in both sleep induction and heat loss.

Increasing levels of anesthesia are thought to produce a progressive loss of brain responsiveness to external stimuli. Here, we present the first report of a state window within anesthesia-induced coma, usually associated with an EEG pattern of burst suppression, during which brain excitability is dramatically increased so that even subliminal stimuli elicit bursts of whole-brain activity. We investigated this phenomenon in vivo using intracellular recordings of both neurons and glia, as well as extracellular calcium and EEG recordings. The results indicate that the bursting activity elicited with mechanical microstimulations, but also with auditory and visual stimuli, is dependent on complex mechanisms, including modulation of excitatory (NMDA) components, gap junction transmission, as well as the extracellular calcium concentration. The occurrence of bursting events is associated with a postburst refractory period that underlies the genesis of the alternating burst-suppression pattern. These findings raise the issue of what burst spontaneity during anesthesia-induced coma means and opens new venues for the handling of comatose patients.

Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) promote homeostatic feeding at times of caloric insufficiency, yet they are rapidly suppressed by food-related sensory cues prior to ingestion. Here we identify a highly selective inhibitory afferent to AgRP neurons that serves as a neural determinant of this rapid modulation. Specifically, GABAergic projections arising from the ventral compartment of the dorsomedial nucleus of the hypothalamus (vDMH) contribute to the pre-consummatory modulation of ARCAgRP neurons. In a manner reciprocal to ARCAgRP neurons, ARC-projecting leptin receptor (LepR)-expressing GABAergic DMH neurons exhibit rapid activation upon availability of food that additionally reflects the relative value of the food. Thus, DMHLepR neurons form part of the sensory network that relays real-time information about the nature and availability of food to dynamically modulate ARCAgRP neuron activity and feeding behavior.