Abstract
Orexins (hypocretins) are two peptides (orexin A and B) produced from the pre-pro-orexin precursor and expressed in a limited region of dorsolateral hypothalamus. Orexins were originally thought to specifically mediate feeding and promote wakefulness, but it is now clear that they participate in a wide range of behavioral and physiological processes under select circumstances. Orexins primarily mediate behavior under situations of high motivational relevance, such as during physiological need states, exposure to threats or reward opportunities. We hypothesize that many behavioral functions of orexins (including regulation of sleep/wake cycling) reflect a fundamentally integrated function for orexins in translating motivational activation into organized suites of psychological and physiological processes supporting adaptive behaviors. We also discuss how numerous forms of neural heterogeneity modulate this function, allowing orexin neurons to organize diverse, adaptive responses in a variety of motivationally relevant situations. Thus, the involvement of orexins in diverse behaviors may reflect a common underlying function for this peptide system.
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Acknowledgements
We thank E. Vought for assistance with figure art and design, and A. Koller for helpful comments. Funding was provided by US National Institutes of Health grants F32 DA026692, K99 DA035251, R01-DA006214, P50 DA015369, R21 DA037744, R21 DA032005 and C06 RR015455, and National Health and Medical Research Council CJ Martin Fellowship 1072706.
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Mahler, S., Moorman, D., Smith, R. et al. Motivational activation: a unifying hypothesis of orexin/hypocretin function. Nat Neurosci 17, 1298–1303 (2014). https://doi.org/10.1038/nn.3810
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DOI: https://doi.org/10.1038/nn.3810
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