Article

Luppi PH, Clement O, Sapin E, Gervasoni D, Peyron C, Leger L et al. The neuronal network responsible for paradoxical sleep and its dysfunctions causing narcolepsy and rapid eye movement (REM) behavior disorder. Sleep Med Rev 15: 153-163

UMR5167 CNRS, Institut Fédératif des Neurosciences de Lyon (IFR 19), Univ Lyon 1, Université de Lyon, Lyon, France.
Sleep Medicine Reviews (Impact Factor: 8.51). 11/2010; 15(3):153-63. DOI: 10.1016/j.smrv.2010.08.002
Source: PubMed

ABSTRACT

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by the loss of muscle atonia during paradoxical (REM) sleep (PS). Conversely, cataplexy, one of the key symptoms of narcolepsy, is a striking sudden episode of muscle weakness triggered by emotions during wakefulness, and comparable to REM sleep atonia. The neuronal dysfunctions responsible for RBD and cataplexy are not known. In the present review, we present the most recent results on the neuronal network responsible for PS. Based on these results, we propose an updated integrated model of the mechanisms responsible for PS and explore different hypotheses explaining RBD and cataplexy. We propose that RBD is due to a specific degeneration of a sub-population of PS-on glutamatergic neurons specifically responsible of muscle atonia, localized in the caudal pontine sublaterodorsal tegmental nucleus (SLD). Another possibility is the occurrence in RBD patients of a specific lesion of the glycinergic/GABAergic pre-motoneurons localized in the medullary ventral gigantocellular reticular nucleus. Conversely, cataplexy in narcoleptics would be due to the activation during waking of the caudal PS-on SLD neurons responsible for muscle atonia. A phasic glutamatergic excitatory pathway from the central amygdala to the SLD PS-on neurons activated during emotion would induce such activation. In normal conditions, the glutamate excitation would be blocked by the simultaneous excitation by the hypocretins of the PS-off GABAergic neurons localized in the ventrolateral periaqueductal gray and the adjacent deep mesencephalic reticular nucleus, gating the activation of the PS-on SLD neurons.

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Available from: Pierre-Hervé Luppi, Feb 06, 2015
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    • "But again, in contrast with copious evidence detailing the role of the brainstem in the generation of twitches[30,32,38,40,41], there is no such evidence detailing a similar role for motor cortex. As with twitches, it is often assumed that the movements of RBD are produced by motor cortex (e.g.,[10,63]). Such statements seem to align with detailed analyses of the complex movements in RBD patients[2,63,64]. "
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    ABSTRACT: Patients with REM sleep behavior disorder (RBD) exhibit increased muscle tone and exaggerated myoclonic twitching during REM sleep. In addition, violent movements of the limbs, and complex behaviors that can sometimes appear to involve the enactment of dreams, are associated with RBD. These behaviors are widely thought to result from a dysfunction involving atonia-producing neural circuitry in the brainstem, thereby unmasking cortically generated dreams. Here we scrutinize the assumptions that led to this interpretation of RBD. In particular, we challenge the assumption that motor cortex produces twitches during REM sleep, thus calling into question the related assumption that motor cortex is primarily responsible for all of the pathological movements of RBD. Moreover, motor cortex is not even necessary to produce complex behavior; for example, stimulation of some brainstem structures can produce defensive and aggressive behaviors in rats and monkeys that are strikingly similar to those reported in human patients with RBD. Accordingly, we suggest an interpretation of RBD that focuses increased attention on the brainstem as a source of the pathological movements and that considers sensory feedback from moving limbs as an important influence on the content of dream mentation.
    Full-text · Article · Jan 2016 · Sleep Medicine Reviews
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    • "Information on brain mechanisms subserving REM-atonia recently arose from animal studies, thanks to experimental brainstem models in cat and rats [3]. Nevertheless, it is still difficult to say to what extent this information can also be applied to the human brain. "
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    ABSTRACT: Rapid Eye Movement (REM) sleep Behaviour Disorder (RBD) is a REM sleep parasomnia characterized by loss of the muscle atonia that typically occurs during REM sleep, therefore allowing patients to act out their dreams. RBD manifests itself clinically as a violent behaviour occurring during the night, and is detected at the polysomnography by phasic and/or tonic muscle activity on the electromyography channel. In absence of neurological signs or central nervous system lesions, RBD is defined as idiopathic. Nevertheless, in a large number of cases the development of neurodegenerative diseases in RBD patients has been described, with the duration of the follow-up representing a fundamental aspect. A growing number of clinical, neurophysiologic and neuropsychological studies aimed to detect early markers of neurodegenerative dysfunction in RBD patients. Anyway, the evidence of impaired cortical activity, subtle neurocognitive dysfunction, olfactory and autonomic impairment and neuroimaging brain changes in RBD patients is challenging the concept of an idiopathic form of RBD, supporting the idea of RBD as an early manifestation of a more complex neurodegenerative process.
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    • "A striking example of this continuity is the preservation throughout life of the stochastic and rhythmical nature of fetal spontaneous motility [10] [43] [44] . This implies that subliminal excitatory fl uctuations may still be taking place within the spinal cord and medulla oblongata, needing now only to receive adequate stimulation from the pontine trigger zone [6] [7] [45] in order to once again reach threshold for effectively evoking motoneuron discharges, as has been nicely demonstrated in chick and mouse embryos [46] [47] . Both in chick embryos and neonatal rats, RBM sleep is clearly a compound state, as illustrated, for instance, by the differential susceptibility of twitching and global bursting to pharmacological interventions [48] . "
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    ABSTRACT: An overview is presented of the literature dealing with sleep-like motility and concomitant neuronal activity patterns throughout the life cycle in vertebrates, ectothermic as well as endothermic. Spontaneous, periodically modulated, neurogenic bursts of non-purposive movements are a universal feature of larval and prenatal behavior, which in endothermic animals (i.e. birds and mammals) continue to occur periodically throughout life. Since the entire body musculature is involved in ever-shifting combinations, it is proposed that these spontaneously active periods be designated as 'rapid-BODY-movement' (RBM) sleep. The term 'rapid-EYE-movement (REM) sleep', characterized by attenuated muscle contractions and reduced tonus, can then be reserved for sleep at later stages of development. Mature stages of development in which sustained muscle atonia is combined with 'paradoxical arousal' of cortical neuronal firing patterns indisputably represent the evolutionarily most recent aspect of REM sleep, but more research with ectothermic vertebrates, such as fi sh, amphibians and reptiles, is needed before it can be concluded (as many prematurely have) that RBM is absent in these species. Evidence suggests a link between RBM sleep in early development and the clinical condition known as 'REM sleep behavior disorder (RBD)', which is characterized by the resurgence of periodic bouts of quasi-fetal motility that closely resemble RBM sleep. Early developmental neuromotor risk factors for RBD in humans also point to a relationship between RBM sleep and RBD.
    No preview · Article · Aug 2015 · Neuroscience Bulletin
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