Heterogeneity of Hypocretin/Orexin Neurons

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.

Fig. 1.. Possible functional heterogeneity of HCRT neurons.

Schematic illustration of proposed functional heterogeneity of HCRT neurons. The unique transcriptional profile, neuronal activity, and synaptic processing and connectivity of HCRT neurons suggest that the multi-functional HCRT neurons can be divided into distinct functional subpopulations in all vertebrates.