The mechanism of different orexin/hypocretin neuronal projections in wakefulness and sleep

Since the discovery of orexin/hypocretin, numerous studies have accumulated evidence demonstrating its key role in various aspects of neuromodulation, including addiction, motivation, and arousal. This paper focuses on the projection of orexin neurons to specific target brain regions through distinct neural pathways to regulate sleep and arousal. We provide a detailed discussion of the projection mechanisms of orexin neurons to downstream neurons, particularly emphasizing their activation of monoaminergic and cholinergic neurons associated with arousal. Additionally, we briefly explore the immune response and inflammatory factors linked to the loss of orexin neurons. Our findings underscore the significance of understanding specific neural projections in the generation and maintenance of arousal, which could guide advancements in neuroscience and lead to new therapeutic opportunities for treating insomnia or narcolepsy.