The hypocretin neuron system: an arousal system in the human brain

Hypocretins are recently discovered neuropeptides produced by a small group of posterior hypothalamic neurons which project widely over the neuroaxis. In this study, we note that hypocretin neuron perikarya in the human brain are localized to the perifornical region of the posterior hypothalamus, extending into the lateral hypothalamus. These neurons lightly innervate all areas of cerebral cortex studied in a variable pattern with denser innervation of association cortex than primary motor or sensory cortex. There is a dense innervation of hypothalamus, locus coeruleus, raphe nuclei, midline thalamus and nucleus of the diagonal band-nucleus basalis complex of the forebrain. This pattern of projections from the hypocretin neurons is compatible with an important role in arousal and the maintenance of the waking state.