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The REM sleep circuit and how its impairment leads to REM sleep behavior disorder

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Abstract

REM sleep is characterized by rapid eye movements, desynchronized electroencephalographic activity, dreams and muscle paralysis that preclude the individual from acting out the action of dreams. REM sleep is generated and modulated by a complex and still poorly understood, neuronal network that involves multiple nuclei and neurotransmission systems. The key structures that generate REM sleep muscle paralysis are the subcoeruleus nucleus in the mesopontine tegmentum and the reticular formation of the ventral medial medulla. Using glutamatergic, GABAergic and glycinergic inputs, direct and indirect projections from these two areas inhibit the motoneurons of the spinal cord resulting in skeletal paralysis in REM sleep. Experimental studies in cats and rodents where the subcoeruleus nucleus and ventral medial medulla were impaired by electrolytic, pharmacological and genetic manipulations have repeatedly produced increased electromyography activity during REM sleep associated with abnormal motor behaviors (e.g., prominent twitching, attack-like behaviors). These animal models represent the pathophysiological substrate of REM sleep behavior disorder, a parasomnia in humans characterized by nightmares and abnormal vigorous behaviors (e.g., prominent jerking, shouting, kicking) linked to excessive phasic and/or tonic electromyographic activity in REM sleep. The extraordinary observation that a sleep disorder is often the first manifestation of a devastating neurodegenerative disease such as Parkinson disease carries important diagnostic implications and opens a window for neuroprotection. This review addresses the neuronal substrates of REM sleep generation and modulation and how its impairment may lead to REM sleep behavior disorder.

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Acknowledgments

I thank Dr. Ellen Gelpi for providing Fig. 10.

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Authors and Affiliations

  1. Neurology Service, Hospital Clínic de Barcelona, C/Villarroel 170, 08036, Barcelona, Spain

    Alex Iranzo

  2. Institut d’Investigació Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Alex Iranzo

  3. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain

    Alex Iranzo

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Correspondence to Alex Iranzo.

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Iranzo, A. The REM sleep circuit and how its impairment leads to REM sleep behavior disorder. Cell Tissue Res 373, 245–266 (2018). https://doi.org/10.1007/s00441-018-2852-8

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  • DOI: https://doi.org/10.1007/s00441-018-2852-8

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