Hypocretin neurons in the lateral hypothalamus project to many brain regions involved in wakefulness, as depicted in Figure 3; however, their projections terminating in thalamus and in cortex show unusual selectivity. In the thalamus, these axons predominantly target the midline-intralaminar nuclei.12 It is perhaps not surprising that these nuclei are targeted by a wakefulness-promoting peptide given their role in arousal and attention. Hypocretin projections to cortex are generally sparse, except for medial prefrontal cortex which receives a denser projection13 that appears to originate from a unique population of hypocretin neurons with minimal collaterals.14
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