Discharge of identified orexin/hypocretin neurons across the sleep-waking cycle.
Although maintained by multiple arousal systems, wakefulness falters if orexin (hypocretin), orexin receptors, or orexin neurons are deficient; narcolepsy results with hypersomnolence or sudden onset of rapid eye movement sleep [or paradoxical sleep (PS)] and loss of muscle tonus. To learn how orexin neurons maintain wakefulness, we recorded neurons in head-fixed rats across the sleep-waking cycle and then labeled them with Neurobiotin to identify them by immunohistochemistry. We show that identified orexin neurons discharge during active waking, when postural muscle tone is high in association with movement, decrease discharge during quiet waking in absence of movement, and virtually cease firing during sleep, when postural muscle tone is low or absent. During PS, they remain relatively silent in association with postural muscle atonia and most often despite phasic muscular twitches. They increase firing before the end of PS and thereby herald by several seconds the return of waking and muscle tone. The orexin neurons would thus stimulate arousal, while antagonizing sleep and muscle atonia.
Lee
Maan Gee
MG
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada.
Hassani
Oum K
OK
Jones
Barbara E
BE
D000200:Action Potentials; D000818:Animals; D001143:Arousal / Q000502:physiology*; D001710:Biotin / Q000031:analogs & derivatives / Q000032:analysis; D004569:Electroencephalography; D004576:Electromyography; D007031:Hypothalamus / Q000166:cytology / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis*; D009043:Motor Activity / Q000502:physiology; D009129:Muscle Tonus / Q000502:physiology*; D009290:Narcolepsy / Q000503:physiopathology; D009474:Neurons / Q000737:chemistry / Q000145:classification / Q000502:physiology*; D009479:Neuropeptides / Q000032:analysis*; D000068797:Orexins; D011187:Posture; D051381:Rats; D020318:Rats, Long-Evans; D012890:Sleep / Q000502:physiology*; D012895:Sleep, REM / Q000502:physiology; D009435:Synaptic Transmission; D014851:Wakefulness / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; C070614:neurobiotin; D001710:Biotin