Heterogeneity of Hypocretin/Orexin Neurons

Dana Sagi, Luis De Lecea, Lior Appelbaum

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


The multifunctional, hypothalamic hypocretin/orexin (HCRT)-producing neurons regulate an array of physiological and behavioral states including arousal, sleep, feeding, emotions, stress, and reward. How a presumably uniform HCRT neuron population regulates such a diverse set of functions is not clear. The role of the HCRT neuropeptides may vary depending on the timing and localization of secretion and neuronal activity. Moreover, HCRT neuropeptides may not mediate all functions ascribed to HCRT neurons. Some could be orchestrated by additional neurotransmitters and neuropeptides that are expressed in HCRT neurons. We hypothesize that HCRT neurons are segregated into genetically, anatomically and functionally distinct subpopulations. We discuss accumulating data that suggest the existence of such HCRT neuron subpopulations that may effectuate the diverse functions of these neurons in mammals and fish.

Original languageEnglish
Pages (from-to)61-74
Number of pages14
JournalFrontiers of Neurology and Neuroscience
StatePublished - 2021

Bibliographical note

Funding Information:
This work was supported by the United States – Israel Binational Science Foundation (BSF, grant No. 2017105) and the National Institutes of Health (NIH, 1RO1MH116470-01A1).

Publisher Copyright:
© 2021 The Author(s).


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