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Mirella Telles Salgueiro Barboni, André Maurício Passos Liber, Anneka Joachimsthaler, Amel Saoudi, Aurélie Goyenvalle, Alvaro Rendon, Jérome E Roger, Dora Fix Ventura, Jan Kremers, Cyrille Vaillend

Altered visual processing in the mdx52 mouse model of Duchenne muscular dystrophy

Neurobiol Dis. 2021 May;152:105288. doi: 10.1016/j.nbd.2021.105288

The mdx52 mouse model of Duchenne muscular dystrophy (DMD) is lacking exon 52 of the DMD gene that is located in a hotspot mutation region causing cognitive deficits and retinal anomalies in DMD patients. This deletion leads to the loss of the dystrophin proteins, Dp427, Dp260 and Dp140, while Dp71 is preserved. The flash electroretinogram (ERG) in mdx52 mice was previously characterized by delayed dark-adapted b-waves. A detailed description of functional ERG changes and visual performances in mdx52 mice is, however, lacking. Here an extensive full-field ERG repertoire was applied in mdx52 mice and WT littermates to analyze retinal physiology in scotopic, mesopic and photopic conditions in response to flash, sawtooth and/or sinusoidal stimuli. Behavioral contrast sensitivity was assessed using quantitative optomotor response (OMR) to sinusoidally modulated luminance gratings at 100% or 50% contrast. The mdx52 mice exhibited reduced amplitudes and delayed implicit times in dark-adapted ERG flash responses, particularly in their b-wave and oscillatory potentials, and diminished amplitudes of light-adapted flash ERGs. ERG responses to sawtooth stimuli were also diminished and delayed for both mesopic and photopic conditions in mdx52 mice and the first harmonic amplitudes to photopic sine-wave stimuli were smaller at all temporal frequencies. OMR indices were comparable between genotypes at 100% contrast but significantly reduced in mdx52 mice at 50% contrast. The complex ERG alterations and disturbed contrast vision in mdx52 mice include features observed in DMD patients and suggest altered photoreceptor-to-bipolar cell transmission possibly affecting contrast sensitivity. The mdx52 mouse is a relevant model to appraise the roles of retinal dystrophins and for preclinical studies related to DMD.

Beatriz Rebollo, Bartosz Telenczuk, Alvaro Navarro-Guzman, Alain Destexhe, Maria V Sanchez-Vives

Modulation of intercolumnar synchronization by endogeneous electric fields in cerebral cortex

Science Advances 7: eabc7772, 2021. doi: 10.1126/sciadv.abc7772

Neurons synaptically interacting in a conductive medium generate extracellular endogenous electric fields (EFs) that reciprocally affect membrane potential. Exogenous EFs modulate neuronal activity, and their clinical applications are being profusely explored. However, whether endogenous EFs contribute to network synchronization remains unclear. We analyzed spontaneously generated slow-wave activity in the cerebral cortex network in vitro, which allowed us to distinguish synaptic from nonsynaptic mechanisms of activity propagation and synchronization. Slow oscillations generated EFs that propagated independently of synaptic transmission. We demonstrate that cortical oscillations modulate spontaneous rhythmic activity of neighboring synaptically disconnected cortical columns if layers are aligned. We provide experimental evidence that these EF-mediated effects are compatible with electric dipoles. With a model of interacting dipoles, we reproduce the experimental measurements and predict that endogenous EF-mediated synchronizing effects should be relevant in the brain. Thus, experiments and models suggest that electric-dipole interactions contribute to synchronization of neighboring cortical columns.

Boudjema Imarazene, Séverine Beille, Elodie Jouanno, Adéle Branthonne, Violette Thermes, Manon Thomas, Amaury Herpin, Sylvie Rétaux, Yann Guiguen

Primordial Germ Cell Migration and Histological and Molecular Characterization of Gonadal Differentiation in Pachón Cavefish Astyanax mexicanus

Sexual Development 2021 Mar 10;1-18. doi: 10.1159/000513378

The genetic regulatory network governing vertebrate gonadal differentiation appears less conserved than previously thought. Here, we investigated the gonadal development of Astyanax mexicanus Pachón cavefish by looking at primordial germ cells (PGCs) migration and proliferation, gonad histology, and gene expression patterns. We showed that PGCs are first detected at the 80% epiboly stage and then reach the gonadal primordium at 1 day post-fertilization (dpf). However, in contrast to the generally described absence of PGCs proliferation during their migration phase, PGCs number in cavefish doubles between early neurula and 8-9 somites stages. Combining both gonadal histology and vasa (germ cell marker) expression patterns, we observed that ovarian and testicular differentiation occurs around 65 dpf in females and 90 dpf in males, respectively, with an important inter-individual variability. The expression patterns of dmrt1, gsdf, and amh revealed a conserved predominant male expression during cavefish gonadal development, but none of the ovarian differentiation genes, i. e., foxl2a, cyp19a1a, and wnt4b displayed an early sexually dimorphic expression, and surprisingly all these genes exhibited predominant expression in adult testes. Altogether, our results lay the foundation for further research on sex determination and differentiation in A. mexicanus and contribute to the emerging picture that the vertebrate sex differentiation downstream regulatory network is less conserved than previously thought, at least in teleost fishes.

Samira Souffi, Christian Lorenzi, Chloé Huetz, Jean-Marc Edeline

La robustesse des réponses neuronales au bruit est une propriété distribuée et prédictible dans tout le système auditif

Robustness to Noise in the Auditory System: A Distributed and Predictable Property. eNeuro, 2021 Feb 25. doi: 10.1523/ENEURO.0043-21.2021

L’Homme et toutes les espèces animales possèdent la faculté de discriminer des sources sonores en présence de bruits environnementaux importants. Ces dernières années, de nombreuses études effectuées chez l’Homme ou l’animal, ont popularisé l’idée que cette capacité reposait essentiellement sur la robustesse des réponses du cortex auditif ; le réseau cortical supposé extraire la source sonore cible au milieu du flux sonore qui nous atteint à chaque instant. Paradoxalement, très peu de travaux ont été réalisés pour déterminer la robustesse des réponses sous-corticales à des sons de communication masqués par du bruit.

Linda Tirou, Mariagiovanna Russo, Hélène Faure, Giuliana Pellegrino, Clément Demongin, Mathieu Daynac, Ariane Sharif, Jeremy Amosse, Soazig Le Lay, Raphaël Denis, Serge Luquet, Mohammed Taouis, Yacir Benomar, Martial Ruat

Sonic Hedgehog receptor Patched deficiency in astrocytes enhances glucose metabolism in mice

Molecular Metabolism, 2021, 26 January. doi: 10.1016/j.molmet.2021.101172

Astrocytes are glial cells proposed as the main Sonic Hedgehog (Shh)-responsive cells in the adult brain. Their roles in mediating Shh functions are still poorly understood. In the hypothalamus, astrocytes support neuronal circuits implicated in the regulation of energy metabolism. Here, we investigated the impact of genetic activation of Shh signaling on hypothalamic astrocytes and characterized its effects on energy metabolism.

Mehdi Belmaati Cherkaoui, Ophélie Vacca, Charlotte Izabelle, Anne‐Cécile Boulay, Claire Boulogne, Cynthia Gillet, Jean‐Vianney Barnier, Alvaro Rendon, Martine Cohen‐Salmon, Cyrille Vaillend

Dp71 contribution to the molecular scaffold anchoring aquaporine-4 channels in brain macroglial cells

Glia 2020, 28 November. doi: 10.1002/glia.23941

Intellectual disability in Duchenne muscular dystrophy has been associated with the loss of dystrophin‐protein 71, Dp71, the main dystrophin‐gene product in the adult brain. Dp71 shows major expression in perivascular macroglial endfeet, suggesting that dysfunctional glial mechanisms contribute to cognitive impairments. In the present study, we investigated the molecular alterations induced by a selective loss of Dp71 in mice, using semi‐quantitative immunogold analyses in electron microscopy and immunofluorescence confocal analyses in brain sections and purified gliovascular units. In macroglial pericapillary endfeet of the cerebellum and hippocampus, we found a drastic reduction (70%) of the polarized distribution of aquaporin‐4 (AQP4) channels, a 50% reduction of β‐dystroglycan, and a complete loss of α1‐syntrophin. Interestingly, in the hippocampus and cortex, these effects were not homogeneous: AQP4 and AQP4ex isoforms were mostly lost around capillaries but preserved in large vessels corresponding to pial arteries, penetrating cortical arterioles, and arterioles of the hippocampal fissure, indicating the presence of Dp71‐independent pools of AQP4 in these vascular structures. In conclusion, the depletion of Dp71 strongly alters the distribution of AQP4 selectively in macroglial perivascular endfeet surrounding capillaries. This effect likely affects water homeostasis and blood–brain barrier functions and may thus contribute to the synaptic and cognitive defects associated with Dp71 deficiency.

Coralie Hérent , Séverine Diem, Gilles Fortin , Julien Bouvier

Absent phasing of respiratory and locomotor rhythms in running mice

Elife 2020. 9:e61919 doi: 10.7554/eLife.61919

Examining whether and how the rhythms of limb and breathing movements interact is highly informative about the mechanistic origin of hyperpnoea during running exercise. However, studies have failed to reveal regularities. In particular, whether breathing frequency is inherently proportional to limb velocity and imposed by a synchronization of breaths to strides is still unclear. Here, we examined respiratory changes during running in the resourceful mouse model. We show that, for a wide range of trotting speeds on a treadmill, respiratory rate increases to a fixed and stable value irrespective of trotting velocities. Respiratory rate was yet further increased during escape-like running and most particularly at gallop. However, we found no temporal coordination of breaths to strides at any speed, intensity, or gait. Our work thus highlights that exercise hyperpnoea can operate, at least in mice and in the presently examined running regimes, without phasic constraints from limb movements.

PubMed or Website : Elife, 1 décembre 2020
Flaria El-Khoury, Jérôme Bignon, Jean-René Martin

Un nouveau petit ARN nucléolaire humain impliqué dans le contrôle de la prolifération cellulaire, jouvence

jouvence, a new human snoRNA involved in the control of cell proliferation. BMC Genomics 21, 817 (2020). doi: 10.1186/s12864-020-07197-3

Les petits ARNs nucléolaires (snoRNAs) sont des ARN-non-codant conservés des archaebactéries au mammifères. Ils sont associés, dans le nucléole, avec des protéines pour former les ribonucléoprotéines. Ils sont subdivisés en deux catégories, les boîtes C/D et les boîtes H/ACA, et servent généralement à modifier les ARN-ribosomaux. Les boîtes H/ACA convertissent l’uridine en pseudouridine. Chez l’humain, certaines pathologies ont été associées à des snoRNAs, alors que plusieurs snoRNAs ont été impliqués dans différents cancers. Récemment, l’équipe de Jean-René Martin (NeuroPSI) a identifié, chez la Drosophile, un nouveau snoRNA, nommé jouvence, et montré que ce dernier, requis dans l’épithélium de l’intestin, est impliqué dans la détermination de la durée de vie. Sa surexpression augmente la durée de vie et protège contre les effect délétères dus au vieillissement, dont notamment les lesions neurodégératives. Comme les snoRNAs sont très conservés au cours de l’évolution, tant structurellement que fonctionnellement, l’orthologue de jouvence a été identifié chez l’humain (il n’était pas annoté dans le génome).

PubMed or Website : BMC Genomics, 23 novembre 2020
Maryline Blin, Julien Fumey, Camille Lejeune, Maxime Policarpo, Julien Leclercq, Stéphane Père, Jorge Torres-Paz, Constance Pierre, Boudjema Imarazene, Sylvie Rétaux

Diversity of olfactory responses and skills in Astyanax mexicanus cavefish populations inhabiting different caves

Diversity 2020, 12(10), 395. doi: 10.3390/d12100395

Understanding the mechanisms of behavioral and sensory adaptation to a novel environement is at stakes both for evolutionary biology and for conservation biology. In an article published in Diversity, researchers of the NeuroPSI Institute have evaluated the olfactory skills of different populations of blind cavefish. Indeed, animals in many phyla are adapted to and thrive in the constant darkness of subterranean environments. To do so, cave animals have presumably evolved mechano- and chemosensory compensations to the loss of vision, as is the case for the blind characiform cavefish, Astyanax mexicanus. Here, we systematically assessed the olfactory capacities of cavefish and surface fish of this species in the lab as well as in the wild, in five different caves in northeastern Mexico. We have used an olfactory setup specially developed to test and record olfactory responses, during fieldwork. Overall cavefish showed lower (i.e., better) olfactory detection thresholds than surface fish. However, wild adult cavefish from the Pachón, Sabinos, Tinaja, Chica and Subterráneo caves showed highly variable responses to the three different odorant molecules they were exposed to. Pachón and Subterráneo cavefish showed the highest olfactory capacities, and Chica cavefish showed no response to the odors presented. We discuss these data, gathered during a special effort in field work in the past five years, with regard to the environmental conditions in which these different cavefish populations live. Our experiments in natural settings document the diversity of cave environments inhabited by a single species of cavefish, A. mexicanus, and highlight the complexity of the plastic and genetic mechanisms that underlie cave adaptation.

PubMed or Website : Diversity, 13 octobre 2020
Bartosz Telenczuk, Maria Telenczuk, Alain Destexhe

Une nouvelle méthode de calcul des signaux électriques cérébraux

A kernel-based method to calculate local field potentials from networks of spiking neurons. Journal of Neuroscience Methods, October 01, 2020. 344:108871. doi: 10.1016/j.jneumeth.2020.108871

Les chercheurs de l'EITN de NeuroPSI ont publié récemment un article dans le Journal of Neuroscience Methods qui propose une nouvelle méthode de calcul des signaux électriques cérébraux. Cette méthode, appelée "Kernel method", permet de calculer les potentiels électriques profonds (Local Field Potential ou LFP) et en surface (Electrocorticogramme ou EcoG) à partir de l’activité des neurones excitateurs et inhibiteurs. Cette méthode se base sur une étude précédente (Telenczuk et al. Scientific Reports 2017), ou les auteurs ont déterminé la relation statistique entre les signaux cérébraux et l’activité des neurones excitateurs et inhibiteurs chez des sujets humains. En reprenant le noyau ("kernel") de cette relation, il est donc possible de calculer ces signaux à partir de la connaissance de l’activité des neurones. Cette méthode sera intégrée dans l'infrastructure EBRAINS du Human Brain Project, pour permettre le calcul de signaux tels que l'EcoG à partir de simulations de parties du cerveau humain. A terme, elle devrait aussi permettre d'envisager le "problème inverse" d'estimer l’activité neuronale à partir de signaux tels que l'EcoG, ce qui représente une perspective intéressante pour l'imagerie de l’activité neuronale chez l'homme.

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