The hypocretins, also known as orexins, are neuropeptides expressed in a few thousand neurons in the lateral hypothalamus that have a key role in arousal stability. Hypocretin deficiency leads to narcolepsy, a sleep disorder characterized by intrusions of sleep into wakefulness. Hypocretin neurons project broadly throughout the brain and control the activity of numerous neurotransmitter and neuromodulator systems. We were first to use optogenetics to control the activity of hypocretin neurons with millisecond precision and established that a main function of the Hcrt system is to increase the probabilty of awakenings. We have now used opto and chemo genetic approaches to map the functional circuitry emanating from hypocretin cells in the lateral hypothalamus. The connectivity of Hcrt cells suggests a potential therapeutic use of selective and non-selective Hypocretin/orexin receptor antagonists in a variety of arousal disorders, including insomnia, anxiety, depression and drug addiction.

Optogenetic control of hypocretin/orexin neurons

248th National Meeting (2014)

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