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Hypocretins (Hcrts) are two secreted neuropeptides, hypocretin-1 and hypocretin-2 that are cleaved from a prepropetide precursor. The locus coeruleus (LC) is adjacent to the fourth ventricle in the brainstem and contains neurons that synthetize the monoamine norepinephrine. Interestingly, physical lesions of the LC do not elicit consistent changes in cortical EEG or behavioral indices of arousal. Optogenetics is a technology in which a genetically encoded neuromodulatory actuator(s) is expressed in a targeted cell type of interest and activated by a specific wavelength of light. Optogenetics has allowed us to make major advances in our understanding of the Hcrt and LC systems, and this technology is applied to dissect other arousal systems as well. The ability to target and selectively manipulate Hcrt and LC neurons allows us the opportunity to study these nuclei in different contexts including rodent models of food intake, addiction, stress, attention, and male sexual arousal.