Jerome M. Siegel

See: https://www.semel.ucla.edu/sleep-research

Narcolepsy: We were first to report hypocretin (orexin) loss in human narcolepsy. More recently we discovered a second neuronal loss in human narcolepsy: All people with narcolepsy have a loss of noradrenergic locus coeruleus neurons.

Opioid addiction:One of the "control" human brains that we acquired for our studies of human narcolepsy had 50% more hypocretin neurons than any of the other control brains and his hypocretin neurons were smaller than those of other "controls". After extensive investigation, we found that this individual was addicted to heroin and that this occurs in all humans with heroin dependence. We then gave morphine to mice and found a similar change. We discovered that opioid addiction was mediated by the hypocretin neurons of the hypothalamus and could be prevented by blocking hypocretin receptors or removing hypocretin neurons.

Sleep, Motor control Our primary interest is in understanding the evolution, function and disorders of REM sleep. We are analyzing the brainstem-forebrain interactions responsible for the control of muscle tone in waking and across the sleep cycle. This is of importance in understanding REM sleep behavior disorder, cataplexy and sleep apnea. We are studying the phylogeny of sleep by investigating the physiology and neurochemistry of sleep in reptiles, marine mammals and other species. We are particularly interested in the role of monoamines in the control of arousal and movement. A major focus of the laboratory is on narcolepsy, its anatomy, pathophysiology and treatment. We have identified the cause of human narcolepsy, a loss of hypocretin cells. We are investigating ways of identifying, controlling and reversing the symptoms of narcolepsy in narcoleptic animals and in humans.