RT Journal Article SR Electronic T1 Glucose Induces Slow-Wave Sleep by Exciting the Sleep-Promoting Neurons in the Ventrolateral Preoptic Nucleus: A New Link between Sleep and Metabolism JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 9900 OP 9911 DO 10.1523/JNEUROSCI.0609-15.2015 VO 35 IS 27 A1 Varin, Christophe A1 Rancillac, Armelle A1 Geoffroy, Hélène A1 Arthaud, Sébastien A1 Fort, Patrice A1 Gallopin, Thierry YR 2015 UL http://www.jneurosci.org/content/35/27/9900.abstract AB Sleep-active neurons located in the ventrolateral preoptic nucleus (VLPO) play a crucial role in the induction and maintenance of slow-wave sleep (SWS). However, the cellular and molecular mechanisms responsible for their activation at sleep onset remain poorly understood. Here, we test the hypothesis that a rise in extracellular glucose concentration in the VLPO can promote sleep by increasing the activity of sleep-promoting VLPO neurons. We find that infusion of a glucose concentration into the VLPO of mice promotes SWS and increases the density of c-Fos-labeled neurons selectively in the VLPO. Moreover, we show in patch-clamp recordings from brain slices that VLPO neurons exhibiting properties of sleep-promoting neurons are selectively excited by glucose within physiological range. This glucose-induced excitation implies the catabolism of glucose, leading to a closure of ATP-sensitive potassium (KATP) channels. The extracellular glucose concentration monitors the gating of KATP channels of sleep-promoting neurons, highlighting that these neurons can adapt their excitability according to the extracellular energy status. Together, these results provide evidence that glucose may participate in the mechanisms of SWS promotion and/or consolidation.SIGNIFICANCE STATEMENT Although the brain circuitry underlying vigilance states is well described, the molecular mechanisms responsible for sleep onset remain largely unknown. Combining in vitro and in vivo experiments, we demonstrate that glucose likely contributes to sleep onset facilitation by increasing the excitability of sleep-promoting neurons in the ventrolateral preoptic nucleus (VLPO). We find here that these neurons integrate energetic signals such as ambient glucose directly to regulate vigilance states accordingly. Glucose-induced excitation of sleep-promoting VLPO neurons should therefore be involved in the drowsiness that one feels after a high-sugar meal. This novel mechanism regulating the activity of VLPO neurons reinforces the fundamental and intimate link between sleep and metabolism.