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Neuroscience. 2016 Nov 12;336:102-113. doi: 10.1016/j.neuroscience.2016.08.046. Epub 2016 Sep 3.

Melanin-concentrating hormone neurons specifically promote rapid eye movement sleep in mice.

Author information

1
Department of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine, Harvard Medical School, Boston, MA 02215, United States. Electronic address: vramalin@bidmc.harvard.edu.
2
Department of Neuroscience, Tufts University School of Medicine, Programs of Neuroscience and Cellular, Molecular and Development Biology, Tufts Sackler School of Graduate Biomedical Sciences, Boston, MA 02111, United States.
3
Department of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine, Harvard Medical School, Boston, MA 02215, United States.
4
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
5
Department of Neurology, Beth Israel Deaconess Medical Center and Division of Sleep Medicine, Harvard Medical School, Boston, MA 02215, United States. Electronic address: csaper@bidmc.harvard.edu.

Abstract

Currently available evidence indicates that neurons containing melanin-concentrating hormone (MCH) in the lateral hypothalamus are critical modulators of sleep-wakefulness, but their precise role in this function is not clear. Studies employing optogenetic stimulation of MCH neurons have yielded inconsistent results, presumably due to differences in the optogenetic stimulation protocols, which do not approximate normal patterns of cell firing. In order to resolve this discrepancy, we (1) selectively activated the MCH neurons using a chemogenetic approach (Cre-dependent hM3Dq expression) and (2) selectively destroyed MCH neurons using a genetically targeted diphtheria toxin deletion method, and studied the changes in sleep-wake in mice. Our results indicate that selective activation of MCH neurons causes specific increases in rapid eye movement (REM) sleep without altering wake or non-REM (NREM) sleep. On the other hand, selective deletions of MCH neurons altered the diurnal rhythm of wake and REM sleep without altering their total amounts. These results indicate that activation of MCH neurons primarily drives REM sleep and their presence may be necessary for normal expression of diurnal variation of REM sleep and wake.

KEYWORDS:

chemogenetics; conditional deletion; feeding; lateral hypothalamus; paradoxical sleep; sleep–wake

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