Rethinking the hypothalamic control of REM sleep
Abstract
The lateral hypothalamus (LH) is generally regarded as a wake-promoting structure, notably through its neurons that release histamine or orexin throughout the brain. However, as early as the 2000s, our team showed that a substantial number of LH neurons express c-Fos, a marker of neuronal activity, following a rebound of paradoxical sleep/rapid eye movement sleep (PS/REM sleep) in rats. Among these so-called PS-on neurons, 75% express GAD67 mRNA and are likely GABAergic inhibitory neurons. Subsequently, subpopulations of PS-on neurons expressing more selective molecular markers were identified, such as melanin-concentrating hormone (MCH) in the lateral hypothalamic area (LHA) or the homeobox protein Lhx6 in the zona incerta (ZI). However, these subpopulations constitute only a small proportion of hypothalamic PS-on neurons, indicating that other, as yet unidentified, neuronal contingents may contribute to the mechanisms underlying PS expression. In this context, we have recently delineated a population of PS-on neurons expressing the transcription factor Meis2 in the ZI. Furthermore, our recent functional data have led us to reassess the classical view that orexin neurons are exclusively associated with wakefulness, whereas MCH neurons are associated with REM sleep. Clearly, an in-depth characterization of each hypothalamic neuronal subpopulation will contribute to a better understanding of the complex neuronal circuits underlying PS and, more broadly, the sleep–wake cycle and its disorders, particularly those related to hypothalamic dysfunction, such as narcolepsy, amyotrophic lateral sclerosis, and certain neurodegenerative diseases. This may open the door to promising translational and preclinical perspectives.
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BibTeX
@article{chancel2026rethinking,
title = {{Rethinking the hypothalamic control of REM sleep}},
author = {Amarine Chancel and Pierre-Hervé Luppi and Patrice Fort},
journal = {Médecine du sommeil},
year = {2026},
month = jun,
doi = {10.1016/j.msom.2026.06.002},
url = {https://hal.science/hal-05672647v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Rethinking the hypothalamic control of REM sleep
AU - Amarine Chancel
AU - Pierre-Hervé Luppi
AU - Patrice Fort
PY - 2026
DA - 2026/06/25
JO - Médecine du sommeil
DO - 10.1016/j.msom.2026.06.002
UR - https://hal.science/hal-05672647v1
AB - The lateral hypothalamus (LH) is generally regarded as a wake-promoting structure, notably through its neurons that release histamine or orexin throughout the brain. However, as early as the 2000s, our team showed that a substantial number of LH neurons express c-Fos, a marker of neuronal activity, following a rebound of paradoxical sleep/rapid eye movement sleep (PS/REM sleep) in rats. Among these so-called PS-on neurons, 75% express GAD67 mRNA and are likely GABAergic inhibitory neurons. Subsequently, subpopulations of PS-on neurons expressing more selective molecular markers were identified, such as melanin-concentrating hormone (MCH) in the lateral hypothalamic area (LHA) or the homeobox protein Lhx6 in the zona incerta (ZI). However, these subpopulations constitute only a small proportion of hypothalamic PS-on neurons, indicating that other, as yet unidentified, neuronal contingents may contribute to the mechanisms underlying PS expression. In this context, we have recently delineated a population of PS-on neurons expressing the transcription factor Meis2 in the ZI. Furthermore, our recent functional data have led us to reassess the classical view that orexin neurons are exclusively associated with wakefulness, whereas MCH neurons are associated with REM sleep. Clearly, an in-depth characterization of each hypothalamic neuronal subpopulation will contribute to a better understanding of the complex neuronal circuits underlying PS and, more broadly, the sleep–wake cycle and its disorders, particularly those related to hypothalamic dysfunction, such as narcolepsy, amyotrophic lateral sclerosis, and certain neurodegenerative diseases. This may open the door to promising translational and preclinical perspectives.
SN - 1769-4493
ER -