Melanin-concentrating hormone neurons discharge in a reciprocal manner to orexin neurons across the sleep–wake cycle

TLDR

Melanin‑concentrating hormone (MCH) neurons are located in the lateral hypothalamus alongside orexin neurons, a region essential for wakefulness, yet knockout and c‑Fos studies suggest MCH may regulate activity and sleep differently from orexin. The study aimed to test whether MCH neurons play a distinct role in sleep‑wake regulation compared to orexin neurons. Researchers recorded neuronal activity across natural sleep‑wake states in head‑fixed rats and identified MCH neurons post hoc using juxtacellular labeling and immunohistochemistry. MCH neurons remained silent during wakefulness, fired selectively during sleep—especially during paradoxical sleep—and exhibited a reciprocal firing pattern to orexin neurons, implying a complementary role that may underlie sleep disorders such as narcolepsy with cataplexy.

Abstract

Neurons containing melanin-concentrating hormone (MCH) are codistributed with neurons containing orexin (Orx or hypocretin) in the lateral hypothalamus, a peptide and region known to be critical for maintaining wakefulness. Evidence from knockout and c-Fos studies suggests, however, that the MCH neurons might play a different role than Orx neurons in regulating activity and sleep-wake states. To examine this possibility, neurons were recorded across natural sleep-wake states in head-fixed rats and labeled by using the juxtacellular technique for subsequent immunohistochemical identification. Neurons identified as MCH+ did not fire during wake (W); they fired selectively during sleep, occasionally during slow wave sleep (SWS) and maximally during paradoxical sleep (PS). As W-Off/Sleep-On, the MCH neurons discharged in a reciprocal manner to the W-On/Sleep-Off Orx neurons and could accordingly play a complementary role to Orx neurons in sleep-wake state regulation and contribute to the pathophysiology of certain sleep disorders, such as narcolepsy with cataplexy.