A role of melanin-concentrating hormone producing neurons in the central regulation of paradoxical sleep

Laure Verret,Laurène Cagnon,Paul Salin,Patrice Fort,Pierre-Hervé Luppi,Romain Goutagny,Denise Salvert,Romuald Boissard,Christelle Peyron,Lucienne Léger

doi:10.1186/1471-2202-4-19

Abstract

BackgroundPeptidergic neurons containing the melanin-concentrating hormone (MCH) and the hypocretins (or orexins) are intermingled in the zona incerta, perifornical nucleus and lateral hypothalamic area. Both types of neurons have been implicated in the integrated regulation of energy homeostasis and body weight. Hypocretin neurons have also been involved in sleep-wake regulation and narcolepsy. We therefore sought to determine whether hypocretin and MCH neurons express Fos in association with enhanced paradoxical sleep (PS or REM sleep) during the rebound following PS deprivation. Next, we compared the effect of MCH and NaCl intracerebroventricular (ICV) administrations on sleep stage quantities to further determine whether MCH neurons play an active role in PS regulation.ResultsHere we show that the MCH but not the hypocretin neurons are strongly active during PS, evidenced through combined hypocretin, MCH, and Fos immunostainings in three groups of rats (PS Control, PS Deprived and PS Recovery rats). Further, we show that ICV administration of MCH induces a dose-dependant increase in PS (up to 200%) and slow wave sleep (up to 70%) quantities.ConclusionThese results indicate that MCH is a powerful hypnogenic factor. MCH neurons might play a key role in the state of PS via their widespread projections in the central nervous system.

Highlights

Peptidergic neurons containing the melanin-concentrating hormone (MCH) and the hypocretins are intermingled in the zona incerta, perifornical nucleus and lateral hypothalamic area
To determine whether the neurons from the lateral hypothalamic area and the perifornical nucleus and those containing hypocretin and MCH are implicated in paradoxical sleep (PS) homeostasis, we combined Fos, hypocretin and MCH immunohistochemistry in rats deprived of PS, with enhanced PS during rebound after PS deprivation and in control condition
Sleep recording data The PS deprivation procedure was effective in producing a near complete elimination of PS in the group of rats perfused after the 72 h of deprivation (PSD group) and in that subjected to the same deprivation and allowed to recover for three hours before perfusion (PSR group)

Summary

Introduction

Peptidergic neurons containing the melanin-concentrating hormone (MCH) and the hypocretins (or orexins) are intermingled in the zona incerta, perifornical nucleus and lateral hypothalamic area. To determine whether the neurons from the lateral hypothalamic area and the perifornical nucleus and those containing hypocretin and MCH are implicated in PS homeostasis, we combined Fos, hypocretin and MCH immunohistochemistry in rats deprived of PS, with enhanced PS during rebound after PS deprivation and in control condition. We chose this method because the examination of Fos, the product of the immediate early gene cfos that is expressed in association with neuronal discharge and entry of Na+ and Ca2+ ions, is well-accepted to study neuronal activity [16,17]. It has been recently and successfully used to localize and characterize the chemical identity of the brainstem neurons responsible for PS generation [18,19,20]

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