Dana Sagi^a, Luis de Lecea^b, Lior Appelbaum^a

^a The Faculty of Life Sciences and the Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat-Gan, Israel; 
^b Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA

© 2021 The Author(s)
Published by S. Karger AG, Basel

• Chapter 6 graphical abstract

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.

• The HCRT system regulates diverse functions, ranging from arousal and feeding to stress and reward.
• Based on their unique gene expression profile, connections, and activity, we propose that the HCRT neurons are divided into distinct functional subpopulations in all vertebrates.
• The relatively simple zebrafish is an attractive model to study the structure and function of subpopulations of HCRT neurons in single neuron resolution.

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