Ventromedial medulla inhibitory neuron inactivation induces REM sleep without atonia and REM sleep behavior disorder

Despite decades of research, there is a persistent debate regarding the localization of GABA/glycine neurons responsible for hyperpolarizing somatic motoneurons during paradoxical (or REM) sleep (PS), resulting in the loss of muscle tone during this sleep state. Combining complementary neuroanatomical approaches in rats, we first show that these inhibitory neurons are localized within the ventromedial medulla (vmM) rather than within the spinal cord. We then demonstrate their functional role in PS expression through local injections of adeno-associated virus carrying specific short-hairpin RNA in order to chronically impair inhibitory neurotransmission from vmM. After such selective genetic inactivation, rats display PS without atonia associated with abnormal and violent motor activity, concomitant with a small reduction of daily PS quantity. These symptoms closely mimic human REM sleep behavior disorder (RBD), a prodromal parasomnia of synucleinopathies. Our findings demonstrate the crucial role of GABA/glycine inhibitory vmM neurons in muscle atonia during PS and highlight a candidate brain region that can be susceptible to α-synuclein-dependent degeneration in RBD patients

Phylogeny of sleep in tetrapods : analysis of evolutionary patterns, electrophysiological and behavioral studies in two squamates species and new methodological perspectives

Le sommeil constitue un comportement vital complexe, identifié chez la quasi-totalité des animaux étudiés. Sur la base d’études princeps dans les années 50 chez le chat et l’homme, le sommeil a pu être séparé clairement en deux états distincts : le sommeil lent et le sommeil paradoxal. Ces deux états ont ainsi été caractérisés sur la base de critères électroencéphalographiques, physiologiques et comportementaux. Basé sur une définition mammalienne, il a ainsi été montré que les mammifères terrestres et les oiseaux, tous deux homéothermes, possédaient ces deux états de sommeil. Cependant, l'origine évolutive de ces deux états reste inconnue et nous ne savons toujours pas s’ils ont évolué de façon indépendante ou s’ils ont été hérités d'un ancêtre commun. Les amphibiens et les reptiles, positionnés à la base des tétrapodes et des amniotes constituent par conséquent, des taxons clés dans la compréhension de l'évolution de ces deux états de sommeil. Afin de mieux comprendre la phylogénie de ces deux états, nous avons réalisé dans un premier temps une revue et méta-analyse de la littérature du sommeil chez ces espèces. Dans un second temps, et dans le but de pouvoir conduire des approches comparatives et ainsi mieux décrire la plasticité du sommeil, nous avons développé un dispositif miniature sans fil permettant d’enregistrer simultanément l’électrophysiologie, la physiologie, la température et le comportement en laboratoire et en milieu naturel. Enfin, nous avons conduit une étude électrophysiologique, physiologique, pharmacologique et comportementale chez deux espèces de squamates (Salvator merianae et Pogona vitticeps). Cette étude nous a permis de montrer que deux états électroencéphalographiques de sommeil existaient chez ces espèces. Cependant, elles ont aussi révélé des divergences phénotypiques importantes au sein même des lézards, ainsi qu’avec le sommeil des mammifères et des oiseaux, démontrant ainsi une origine commune mais complexe des deux états de sommeilSleep is a vital and complex behavior, identified in nearly all animals. Based on studies on cats and humans conducted in the 50’s, sleep was separated into two distinct sleep states: slow wave sleep and paradoxical sleep (or REM sleep). Those two states were identified based on electroencephalographic, physiological and behavioral parameters. Based on this mammalian definition, it has been demonstrated that those two states exist in terrestrial mammals and birds, both homeotherms. However, the evolutive origin of these sleeps states remains unknown and we do not know whether they evolved independently or if they were inherited from a common ancestor. Amphibians and reptiles are respectively positioned at the base of the tetrapod and the amniote tree. Therefore, they constitute key taxa in the understanding of the origin of these states. In order to understand the phylogeny of these states, we first performed an exhaustive review and meta-analysis of the sleep literature in these groups. Next, in order to be able to conduct comparative approaches and better understand the sleep plasticity, we developed a standalone miniature device to record electrophysiology, physiology, temperature, and behavior simultaneously and this under both lab and field conditions. Finally, we conducted an electrophysiological, physiological, pharmacological and behavioral study of two squamates species (Salvator merianae and Pogona vitticeps). This study revealed that two electro-encephalographical sleep states exist in these species. However, they also showed that the phenotype of these states diverged between the two lizards and between the lizards on the one hand and mammals and birds on the other hand. This would suggest a common, but complex, origin of these two sleep state

Phylogénie du sommeil chez les tétrapodes : analyse de patterns évolutifs, études électrophysiologiques et comportementales chez deux espèces de squamates et nouvelles perspectives méthodologiques

Sleep is a vital and complex behavior, identified in nearly all animals. Based on studies on cats and humans conducted in the 50’s, sleep was separated into two distinct sleep states: slow wave sleep and paradoxical sleep (or REM sleep). Those two states were identified based on electroencephalographic, physiological and behavioral parameters. Based on this mammalian definition, it has been demonstrated that those two states exist in terrestrial mammals and birds, both homeotherms. However, the evolutive origin of these sleeps states remains unknown and we do not know whether they evolved independently or if they were inherited from a common ancestor. Amphibians and reptiles are respectively positioned at the base of the tetrapod and the amniote tree. Therefore, they constitute key taxa in the understanding of the origin of these states. In order to understand the phylogeny of these states, we first performed an exhaustive review and meta-analysis of the sleep literature in these groups. Next, in order to be able to conduct comparative approaches and better understand the sleep plasticity, we developed a standalone miniature device to record electrophysiology, physiology, temperature, and behavior simultaneously and this under both lab and field conditions. Finally, we conducted an electrophysiological, physiological, pharmacological and behavioral study of two squamates species (Salvator merianae and Pogona vitticeps). This study revealed that two electro-encephalographical sleep states exist in these species. However, they also showed that the phenotype of these states diverged between the two lizards and between the lizards on the one hand and mammals and birds on the other hand. This would suggest a common, but complex, origin of these two sleep statesLe sommeil constitue un comportement vital complexe, identifié chez la quasi-totalité des animaux étudiés. Sur la base d’études princeps dans les années 50 chez le chat et l’homme, le sommeil a pu être séparé clairement en deux états distincts : le sommeil lent et le sommeil paradoxal. Ces deux états ont ainsi été caractérisés sur la base de critères électroencéphalographiques, physiologiques et comportementaux. Basé sur une définition mammalienne, il a ainsi été montré que les mammifères terrestres et les oiseaux, tous deux homéothermes, possédaient ces deux états de sommeil. Cependant, l'origine évolutive de ces deux états reste inconnue et nous ne savons toujours pas s’ils ont évolué de façon indépendante ou s’ils ont été hérités d'un ancêtre commun. Les amphibiens et les reptiles, positionnés à la base des tétrapodes et des amniotes constituent par conséquent, des taxons clés dans la compréhension de l'évolution de ces deux états de sommeil. Afin de mieux comprendre la phylogénie de ces deux états, nous avons réalisé dans un premier temps une revue et méta-analyse de la littérature du sommeil chez ces espèces. Dans un second temps, et dans le but de pouvoir conduire des approches comparatives et ainsi mieux décrire la plasticité du sommeil, nous avons développé un dispositif miniature sans fil permettant d’enregistrer simultanément l’électrophysiologie, la physiologie, la température et le comportement en laboratoire et en milieu naturel. Enfin, nous avons conduit une étude électrophysiologique, physiologique, pharmacologique et comportementale chez deux espèces de squamates (Salvator merianae et Pogona vitticeps). Cette étude nous a permis de montrer que deux états électroencéphalographiques de sommeil existaient chez ces espèces. Cependant, elles ont aussi révélé des divergences phénotypiques importantes au sein même des lézards, ainsi qu’avec le sommeil des mammifères et des oiseaux, démontrant ainsi une origine commune mais complexe des deux états de sommei

Instrumentation pour la caractérisation du sommeil chez l'animal, du laboratoire au milieu naturel

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Insights into paradoxical (REM) sleep homeostatic regulation in mice using an innovative automated sleep deprivation method

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Locomotor-feeding coupling during prey capture in a lizard (Gerrhosaurus major): effects of prehension mode

International audienceIn tetrapods, feeding behaviour in general, and prey capture in particular, involves two anatomical systems: the feeding system and the locomotor system. Although the kinematics associated with the movements of each system have been investigated in detail independently, the actual integration between the two systems has received less attention. Recently, the independence of the movements of the jaw and locomotor systems was reported during tongue-based prey capture in an iguanian lizard (Anolis carolinensis), suggesting a decoupling between the two systems. Jaw prehension, on the other hand, can be expected to be dependent on the movements of the locomotor system to a greater degree. To test for the presence of functional coupling and integration between the jaw and locomotor systems, we used the cordyliform lizard Gerrhosaurus major as a model species because it uses both tongue and jaw prehension. Based on a 3-D kinematic analysis of the movements of the jaws, the head, the neck and the forelimbs during the approach and capture of prey, we demonstrate significant correlations between the movements of the trophic and the locomotor systems. However, this integration differs between prehension modes in the degree and the nature of the coupling. In contrast to our expectations and previous data for A. carolinensis, our data indicate a coupling between feeding and locomotor systems during tongue prehension. We suggest that the functional integration between the two systems while using the tongue may be a consequence of the relatively slow nature of tongue prehension in this species

Separating the effects of prey size and speed on the kinematics of prey capture in the omnivorous lizard Gerrhosaurus major

International audienceFeeding behavior is known to be modulated as prey properties change. During prey capture, external prey properties, including size and mobility, are likely some of the most important components in predator–prey interactions. Whereas prey size has been demonstrated to elicit modulation of jaw movements during capture, how prey speed affects the approach and capture of prey remains unknown. We quantified the kinematics associated with movements of both the feeding and locomotor systems during prey capture in a lizard, Gerrhosaurus major, while facing prey differing in size and mobility (newborn mice, grasshoppers, and mealworms). Our data show that the feeding and locomotor systems were recruited differently in response to changes in the size or speed of the prey. The timing of jaw movements and of the positioning of the head are affected by changes in prey size—and speed, to a lesser extent. Changes in prey speed resulted in concomitant changes in the speed of strike and an early and greater elevation of the neck. External prey properties, and prey mobility in particular, are relevant in predator–prey interactions and elicit specific responses in different functional systems

Slow waves promote sleep-dependent plasticity and functional recovery after stroke.

Functional recovery after stroke is associated with a remapping of neural circuits. This reorganization is often associated with low frequency high amplitude oscillations in the peri-infarct zone in both rodents and humans. These oscillations are reminiscent of sleep slow waves (SW) and suggestive of a role for sleep in brain plasticity that occur during stroke recovery, however, direct evidence is missing. Using a stroke model in male mice, we showed that stroke was followed by a transient increase in NREM sleep accompanied by reduced amplitude and slope of ipsilateral NREM sleep SW. We next used 5 ms optical activation of Channelrhodopsin 2-expressing pyramidal neurons, or 200 ms silencing of Archeorhodopsin T-expressing pyramidal neurons, to generate local cortical UP, or DOWN, states, respectively, both sharing similarities with spontaneous NREM SW in freely-moving mice. Importantly, we found that single optogenetically-evoked SW (SWopto) in the peri-infarct zone, randomly distributed during sleep, significantly improved fine motor movements of the limb corresponding to the sensorimotor stroke lesion site, as compared to spontaneous recovery and control conditions, while motor strength remained unchanged. In contrast, SWopto during wakefulness had no effect. Furthermore, chronic SWopto during sleep were associated with local axonal sprouting as revealed by the increase of anatomical pre- and post-synaptic markers in the peri-infarct zone and corresponding contra-lesional areas to cortical circuit reorganization during stroke recovery. These results support a role for sleep SW in cortical circuit plasticity and sensorimotor recovery after stroke and provide a clinically-relevant framework for rehabilitation strategies using neuromodulation during sleep.SIGNIFICANCE STATEMENTBrain stroke is one of the leading causes of death and major disabilities in elderly worldwide. A better understanding of the pathophysiological mechanisms underlying spontaneous brain plasticity after stroke, together with an optimization of rehabilitative strategies, are essential to improve stroke treatments. Here, we investigate the role of optogenetically-induced sleep slow waves in an animal model of ischemic stroke and identify sleep as a window for post-stroke intervention that promotes neuroplasticity and facilitates sensorimotor recovery

Prey capture in lizards: differences in jaw-neck-forelimb coordination

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Unsupervised Online Classifier in Sleep Scoring for Sleep Deprivation Studies

International audienceSTUDY OBJECTIVE:This study was designed to evaluate an unsupervised adaptive algorithm for real-time detection of sleep and wake states in rodents.DESIGN:We designed a Bayesian classifier that automatically extracts electroencephalogram (EEG) and electromyogram (EMG) features and categorizes non-overlapping 5-s epochs into one of the three major sleep and wake states without any human supervision. This sleep-scoring algorithm is coupled online with a new device to perform selective paradoxical sleep deprivation (PSD).SETTINGS:Controlled laboratory settings for chronic polygraphic sleep recordings and selective PSD.PARTICIPANTS:Ten adult Sprague-Dawley rats instrumented for chronic polysomnographic recordings.MEASUREMENTS:The performance of the algorithm is evaluated by comparison with the score obtained by a human expert reader. Online detection of PS is then validated with a PSD protocol with duration of 72 hours.RESULTS:Our algorithm gave a high concordance with human scoring with an average κ coefficient > 70%. Notably, the specificity to detect PS reached 92%. Selective PSD using real-time detection of PS strongly reduced PS amounts, leaving only brief PS bouts necessary for the detection of PS in EEG and EMG signals (4.7 ± 0.7% over 72 h, versus 8.9 ± 0.5% in baseline), and was followed by a significant PS rebound (23.3 ± 3.3% over 150 minutes).CONCLUSIONS:Our fully unsupervised data-driven algorithm overcomes some limitations of the other automated methods such as the selection of representative descriptors or threshold settings. When used online and coupled with our sleep deprivation device, it represents a better option for selective PSD than other methods like the tedious gentle handling or the platform method