Sleep Research | Semel Institute for Neuroscience and Human Behavior

Center for Sleep Research

Our goal is to better understand the evolution, function and disorders of sleep.

A major focus of the laboratory is on the peptide hypocretin (orexin), whose loss is responsible for narcolepsy. Our work on the control of sleep and motor activity has relevance to an understanding of sleep apnea, REM sleep behavior disorder, restless legs syndrome and nocturnal bruxism.

Director: Jerome Siegel

Publications -- Narcolepsy

"Opiates increase the number of hypocretin-producing cells in human and mouse brain and reverse cataplexy in a mouse model of narcolepsy." Science Translational Medicine 2018
"Striking cessation of cataplexy by opioids." J Sleep Res 2018
"Interactions of the histamine and hypocretin systems in CNS disorders." Nat Rev Neurol 2015
"Cataplexy--clinical aspects, pathophysiology and management strategy." Nat Rev Neurol 2014
"Gender differences between hypocretin/orexin knockout and wild type mice: age, body weight, body composition, metabolic markers, leptin and insulin resistance." J Neurochem 2014
"Greatly increased numbers of histamine cells in human narcolepsy with cataplexy." Ann Neurol 2013
"Coexistence of narcolepsy and Alzheimer's disease." Neurobiol Aging 2012
"Highly specific role of hypocretin (orexin) neurons: differential activation as a function of diurnal phase, operant reinforcement versus operant avoidance and light level." J Neurosci 2011
"Role of the hypocretin (orexin) receptor 2 (Hcrt-r2) in the regulation of hypocretin level and cataplexy." J Neurosci 2011
"A consensus definition of cataplexy in mouse models of narcolepsy." Sleep 2009
"Localized loss of hypocretin (orexin) cells in narcolepsy without cataplexy." Sleep 2009
"Hypocretin (orexin) cell loss in Parkinson's disease." Brain 2007
"Systemic and nasal delivery of orexin-A (Hypocretin-1) reduces the effects of sleep deprivation on cognitive performance in nonhuman primates." J Neurosci 2007
"Narcolepsy and the hypocretin system--where motion meets emotion." Nat Clin Pract Neurol 2006
"Narp immunostaining of human hypocretin (orexin) neurons: loss in narcolepsy." Neurology 2005
"Pattern of hypocretin (orexin) soma and axon loss, and gliosis, in human narcolepsy." Brain Pathol 2003
"Human narcolepsy is linked to reduced number, size and synaptic bouton density In hypocretin-2 labeled neurons." Society for Neuroscience 2000
"Narcolepsy" Scientific American 2000
"Recent developments in narcolepsy research, an explanation for patients and the general public" Narcolepsy Network Newsletter 2000
"Reduced number of hypocretin neurons in human narcolepsy." Neuron 2000

Publications -- Sleep

"Do all mammals dream?" J Comp Neurol 2020
"Sleep under evolutionarily relevant conditions." Sleep Med 2020
"Eye state asymmetry during aquatic unihemispheric slow wave sleep in northern fur seals (Callorhinus ursinus)." PLoS One 2019
"Sleep in aquatic mammals" Handbook of Sleep Research 2019
"Sleep timing and duration in indigenous villages with and without electric lighting on Tanna Island, Vanuatu." Sci Rep 2019
"Fur Seals Suppress REM Sleep for Very Long Periods without Subsequent Rebound." Curr Biol 2018
"Sleep phylogenetic evolution and ontogeny" 2018
"The influence of age- and sex-specific labor demands on sleep in Namibian agropastoralists." Sleep Health 2018
"Inactivity/sleep in two wild free-roaming African elephant matriarchs – Does large body size make elephants the shortest mammalian sleepers?" PLOS ONE 2017
"Rapid eye movement sleep" Principles and Practice of Sleep Medicine 2017
"Sleep in animals: a state of adaptive inactivity" Principles and Practice of Sleep Medicine 2017
"Sleep in the northern fur seal." Curr Opin Neurobiol 2017
"Natural sleep and its seasonal variations in three pre-industrial societies." Curr Biol 2015
"Symmetrical serotonin release during asymmetrical slow-wave sleep: implications for the neurochemistry of sleep-waking states." J Neurosci 2013
"The evolution of sleep" Encyclopedia of Sleep 2013
"Evolution. Suppression of sleep for mating." Science 2012
"Sleep in animals: a state of adaptive inactivity" Principles and Practice of Sleep Medicine 2011
"Are sleeping pills good for you?" Huffington Post 2010
"How much sleep do we actually need?" Huffington Post 2010
"Behavioral sleep in the walrus." Behav Brain Res 2009
"Sleep viewed as a state of adaptive inactivity." Nat Rev Neurosci 2009
"Electroencephalogram asymmetry and spectral power during sleep in the northern fur seal." J Sleep Res 2008
"Unearthing the phylogenetic roots of sleep." Curr Biol 2008
"Animal behaviour: continuous activity in cetaceans after birth." Nature 2005
"Clues to the functions of mammalian sleep." Nature 2005
"Continuous activity in cetaceans after birth" Nature 2005
"The REM sleep-memory consolidation hypothesis." Science 2001

Publications -- Sleep Mechanisms

"Sex- and Age-dependent Differences in Sleep-wake Characteristics of Fisher-344 Rats." Neuroscience 2020
"Striatal histamine mechanism in the pathogenesis of restless legs syndrome." Sleep 2020
"Characteristics of Sleep-Active Neurons in the Medullary Parafacial Zone in Rats." Sleep 2018
"Diurnal fluctuation in the number of hypocretin/orexin and histamine producing: Implication for understanding and treating neuronal loss" PLOS ONE 2017
"Motor hyperactivity of the iron-deficient rat - an animal model of restless legs syndrome." Mov Disord 2017
"Monoamine Release during Unihemispheric Sleep and Unihemispheric Waking in the Fur Seal." Sleep 2016
"Obstructive sleep apnea is associated with low GABA and high glutamate in the insular cortex" Journal of Sleep Research 2016
"Control of sleep in mammals (poster)" Nature Neuroscience Reviews 2015
"Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction." Nat Commun 2013
"REM sleep: a biological and psychological paradox." Sleep Med Rev 2011
"Sleep deprivation under sustained hypoxia protects against oxidative stress." Free Radic Biol Med 2011
"Behavioral response and transmitter release during atonia elicited by medial medullary stimulation." J Neurophysiol 2010
"Illuminating the locus coeruleus: control of posture and arousal." Nat Neurosci 2010
"Short-term total sleep deprivation in the rat increases antioxidant responses in multiple brain regions without impairing spontaneous alternation behavior." Behav Brain Res 2010
"The neurobiology of sleep." Semin Neurol 2009
"An endogenous glutamatergic drive onto somatic motoneurons contributes to the stereotypical pattern of muscle tone across the sleep-wake cycle." J Neurosci 2008
"Rapid changes in glutamate levels in the posterior hypothalamus across sleep-wake states in freely behaving rats." Am J Physiol Regul Integr Comp Physiol 2008
"Cortical acetylcholine release is lateralized during asymmetrical slow-wave sleep in northern fur seals." J Neurosci 2007
"The stuff dreams are made of: anatomical substrates of REM sleep." Nat Neurosci 2006
"Behavioral correlates of activity in identified hypocretin/orexin neurons." Neuron 2005
"Cataplexy-active neurons in the hypothalamus: implications for the role of histamine in sleep and waking behavior." Neuron 2004
"Hypocretin (orexin): role in normal behavior and neuropathology." Annu Rev Psychol 2004