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The Journal of Neuroscience, April 20, 2005, 25(16):4127-4130; doi:10.1523/JNEUROSCI.0666-05.2005

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The Wake-Promoting Hypocretin/Orexin Neurons Change Their Response to Noradrenaline after Sleep Deprivation

Jeremy Grivel,¹ Vesna Cvetkovic,¹ Laurence Bayer,¹ Danièle Machard,¹ Irene Tobler,² Michel Mühlethaler,¹ and Mauro Serafin¹

¹Département des Neurosciences fondamentales, Centre Médical Universitaire, 1211 Geneva 4, Switzerland, and ²Institute of Pharmacology and Toxicology, University of Zurich, 8057 Zurich, Switzerland

Sleep deprivation is accompanied by the progressive development of an irresistible need to sleep, a phenomenon whose mechanism has remained elusive. Here, we identified for the first time a reflection of that phenomenon in vitro by showing that, after a short 2 h period of total sleep deprivation, the action of noradrenaline on the wake-promoting hypocretin/orexin neurons changes from an excitation to an inhibition. We propose that such a conspicuous modification of responsiveness should contribute to the growing sleepiness that accompanies sleep deprivation.

Key words: arousal; hypothalamus; sleep; waking; noradrenaline; orexin

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Received Jan 12, 2005; revised March 14, 2005; accepted March 15, 2005.

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