June 12, 2005 UCLA/Veterans Affairs neuroscientists have pinpointed the electrical "signature" of the brain cells whose loss causes human narcolepsy, and made the first recordings of their activity. Made in freely moving rats in waking and across the sleep cycle, these recordings show hypocretin neurons are active during excitement generated by positive emotions and by interest in one's surroundings. The study also reveals that these cells counteract weakness brought on by positive emotion and play a key role in maintaining brain alertness.
Human narcolepsy is caused by a loss of cells in the brain's hypothalamus that contain the protein hypocretin (also called orexin). This discovery was made by this same group and colleagues and published in September 2000. In human narcoleptics, cataplexy, a sudden loss of muscle tone that can cause an individual to fall to the floor, is triggered by laughter, sexual activity and related pleasant activities, but not by pain or aversive situations. In normal humans, a similar weakness accompanies laughter ("doubling up with laughter") and certain emotions, but the weakness is limited, never resulting in cataplexy. The current study reveals the neuronal mechanisms responsible for maintaining alertness and limiting emotionally triggered weakness.
The study explains the persistent sleepiness of narcolepsy and reveals the existence of a brain system that is most active during rewarding, positive experiences. Preliminary work indicates that replacement of the natural wake-inducing chemical hypocretin can prevent cataplexy and reverse the sleepiness of narcolepsy.
The senior author is Dr. Jerome Siegel, professor-in-residence at the UCLA Neuropsychiatric Institute and chief of neurobiology research at the VA Greater Los Angeles Healthcare System, Sepulveda.
The research appears in the June 2 edition of Neuron.
Funding was provided by the National Institutes of Health and Medical Research Service of the Department of Veterans Affairs.
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