These findings identify a common neural substrate underlying diverse general anesthetics drugs and natural sleep and reveal a crucial role of the neuroendocrine system in regulating global brain states

A Common Neuroendocrine Substrate for Diverse General Anesthetics and Sleep. Li-Feng Jiang-Xie et al. Neuron, April 18, 2019. https://doi.org/10.1016/j.neuron.2019.03.033

Highlights
    •     General-anesthesia-activated neurons (AANs) are identified in hypothalamus
    •     AANs consist mainly of neuroendocrine cells in and near the supraoptic nucleus
    •     Activation of AANs promotes slow-wave sleep and extends general anesthesia
    •     Inhibition of AANs shortens general anesthesia and disrupts natural sleep

Summary: How general anesthesia (GA) induces loss of consciousness remains unclear, and whether diverse anesthetic drugs and sleep share a common neural pathway is unknown. Previous studies have revealed that many GA drugs inhibit neural activity through targeting GABA receptors. Here, using Fos staining, ex vivo brain slice recording, and in vivo multi-channel electrophysiology, we discovered a core ensemble of hypothalamic neurons in and near the supraoptic nucleus, consisting primarily of neuroendocrine cells, which are persistently and commonly activated by multiple classes of GA drugs. Remarkably, chemogenetic or brief optogenetic activations of these anesthesia-activated neurons (AANs) strongly promote slow-wave sleep and potentiates GA, whereas conditional ablation or inhibition of AANs led to diminished slow-wave oscillation, significant loss of sleep, and shortened durations of GA. These findings identify a common neural substrate underlying diverse GA drugs and natural sleep and reveal a crucial role of the neuroendocrine system in regulating global brain states.