Viral Vector Induction of CREB Expression in the Periaqueductal Gray Induces a Predator Stress-Like Pattern of Changes in pCREB Expression, Neuroplasticity, and Anxiety in Rodents

Predator stress is lastingly anxiogenic. Phosphorylation of CREB to pCREB (phosphorylated cyclic AMP response element binding protein) is increased after predator stress in fear circuitry, including in the right lateral column of the PAG (periaqueductal gray). Predator stress also potentiates right but not left CeA-PAG (central amygdala-PAG) transmission up to 12 days after stress. The present study explored the functional significance of pCREB changes by increasing CREB expression in non-predator stressed rats through viral vectoring, and assessing the behavioral, electrophysiological and pCREB expression changes in comparison with handled and predator stressed controls. Increasing CREB expression in right PAG was anxiogenic in the elevated plus maze, had no effect on risk assessment, and increased acoustic startle response while delaying startle habituation. Potentiation of the right but not left CeA-PAG pathway was also observed. pCREB expression was slightly elevated in the right lateral column of the PAG, while the dorsal and ventral columns were not affected. The findings of this study suggest that by increasing CREB and pCREB in the right lateral PAG, it is possible to produce rats that exhibit behavioral, brain, and molecular changes that closely resemble those seen in predator stressed rats

Gaze Behaviour During Collision Avoidance Between Walkers: A Preliminary Study to Design an Experimental Platform

International audienceWhen walking, vision is the main source of information that allows us to navigate safely by detecting potential collisions with other walkers. In order to gain a better understanding of the relationship between gaze activity and kinematics of motion during pedestrian interactions, we present in this paper a preliminary study towards designing a more comprehensive experimental platform. In this study, participants are asked to avoid collisions with an upcoming virtual character using a joystick, while we measure their gaze behaviours using an eye-tracker. As we are interested in the effects of potential collisions on gaze activity, i.e., where and when participants look to avoid potential future collisions, we display in our experiment a virtual character for which we vary the initial Time To Closest Approach (ttca) and Distance of Closest Approach (dca) values, to change its risk of collision with our participant. We then measure participant trajectory adjustments and gaze activity during the interaction. Our preliminary results show which type of data this platform produces, and demonstrate the interest of designing more comprehensive experiences and tools to analyze both gaze activity and kinematics

HDAC6 Regulates Glucocorticoid Receptor Signaling in Serotonin Pathways with Critical Impact on Stress Resilience

Genetic variations in certain components of the glucocorticoid receptor (GR) chaperone complex have been associated with the development of stress-related affective disorders and individual variability in therapeutic responses to antidepressants. Mechanisms that link GR chaperoning and stress susceptibility are not well understood. Here, we show that the effects of glucocorticoid hormones on socioaffective behaviors are critically regulated via reversible acetylation of Hsp90, a key component of the GR chaperone complex. We provide pharmacological and genetic evidence indicating that the cytoplasmic lysine deacetylase HDAC6 controls Hsp90 acetylation in the brain, and thereby modulates Hsp90–GR protein–protein interactions, as well as hormone- and stress-induced GR translocation, with a critical impact on GR downstream signaling and behavior. Pet1-Cre-driven deletion of HDAC6 in serotonin neurons, the densest HDAC6-expressing cell group in the mouse brain, dramatically reduced acute anxiogenic effects of the glucocorticoid hormone corticosterone in the open-field, elevated plus maze, and social interaction tests. Serotonin-selective depletion of HDAC6 also blocked the expression of social avoidance in mice exposed to chronic social defeat and concurrently prevented the electrophysiological and morphological changes induced, in serotonin neurons, by this murine model of traumatic stress. Together, these results identify HDAC6 inhibition as a potential new strategy for proresilience and antidepressant interventions through regulation of the Hsp90–GR heterocomplex and focal prevention of GR signaling in serotonin pathways. Our data thus uncover an alternate mechanism by which pan-HDAC inhibitors may regulate stress-related behaviors independently of their action on histones

Crowd Navigation in VR: exploring haptic rendering of collisions

International audienceVirtual reality (VR) is a valuable experimental tool for studying human movement, including the analysis of interactions during locomotion tasks for developing crowd simulation algorithms. However, these studies are generally limited to distant interactions in crowds, due to the difficulty of rendering realistic sensations of collisions in VR. In this work, we explore the use of wearable haptics to render contacts during virtual crowd navigation. We focus on the behavioural changes occurring with or without haptic rendering during a navigation task in a dense crowd, as well as on potential after-effects introduced by the use haptic rendering. Our objective is to provide recommendations for designing VR setup to study crowd navigation behaviour. To this end, we designed an experiment (N=23) where participants navigated in a crowded virtual train station without, then with, and then again without haptic feedback of their collisions with virtual characters. Results show that providing haptic feedback improved the overall realism of the interaction, as participants more actively avoided collisions. We also noticed a significant after-effect in the users' behaviour when haptic rendering was once again disabled in the third part of the experiment. Nonetheless, haptic feedback did not have any significant impact on the users' sense of presence and embodiment

Port-en-Bessin-Huppain, Commes – Le Mont Castel

Depuis quatre ans, le site du Mont Castel fait l’objet de fouilles archéologiques programmées à la fin de l’été. En 2018 la fouille a concerné l’étude d’un vaste horreum et l’étude des abords du rempart, à proximité de l’habitat de l’âge du Bronze. C’est dans ce secteur qu’a été mis au jour, en début de campagne, un dépôt du Bronze final 3a comportant une trentaine d’objets en bronze dans un vase en céramique. Ce dépôt est une découverte de premier plan au niveau national puisque intègre et e..

The Front-End of the NOEMA Interferometer

The IRAM Plateau de Bure Interferometer (PdBI) is being upgraded to a new powerful millimeter-wave radio astronomy facility called the NOrthern Extended Millimeter Array (NOEMA) which will double the number of the 15-m diameter antennas from six to 12. All antennas will be equipped with a new generation of dual-polarization Front-End covering the 72-373-GHz frequency range with four independent receivers integrated into a single cryostat. All receivers utilize sideband separating (2SB) superconductor-insulator-superconductor (SIS) mixers, each of which delivers two ~7.7-GHz-wide intermediate frequency (IF) outputs per polarization channel, thus increasing the total IF bandwidth which can be processed with a single setting of the interferometer from 8 GHz (2 × 4 GHz delivered by the existing PdBI Front-End) to ~31 GHz (4 × 7.7 GHz delivered by the NOEMA Front-End). The first of the new NOEMA antennas (Ant. 7) has recently been completed and the first NOEMA Front-End successfully developed and installed in it. For the coming years, our goal is to upgrade all of the Front-Ends currently installed on the six existing PdBI antennas to the new NOEMA standard and to build six additional ones (plus one spare) for the new NOEMA antennas. In this paper, we describe the design, fabrication, and assembly of the Front-End we have developed for NOEMA Antenna 7. The instrument has state-of-the-art performance and sets a new standard in the post-ALMA generation technology

Port-en-Bessin-Huppain – Le Mont Castel

Depuis trois ans, le site du Mont Castel fait l’objet de fouilles archéologiques programmées à la fin de l’été. Cette année, c’est principalement l’occupation de la fin de l’indépendance gauloise qui a fait l’objet d’un travail de fond. Il est désormais possible de dresser dans ces grandes lignes les modalités d’occupation du site. Nous rappellerons toutefois, avant de présenter l’occupation de La Tène D2b, que le site est fortifié et occupé dès le Bronze final IIIa et fait l’objet durant le ..

Chronic Citalopram Administration Causes a Sustained Suppression of Serotonin Synthesis in the Mouse Forebrain

BACKGROUND:Serotonin (5-HT) is a neurotransmitter with important roles in the regulation of neurobehavioral processes, particularly those regulating affect in humans. Drugs that potentiate serotonergic neurotransmission by selectively inhibiting the reuptake of serotonin (SSRIs) are widely used for the treatment of psychiatric disorders. Although the regulation of serotonin synthesis may be an factor in SSRI efficacy, the effect of chronic SSRI administration on 5-HT synthesis is not well understood. Here, we describe effects of chronic administration of the SSRI citalopram (CIT) on 5-HT synthesis and content in the mouse forebrain. METHODOLOGY/PRINCIPAL FINDINGS:Citalopram was administered continuously to adult male C57BL/6J mice via osmotic minipump for 2 days, 14 days or 28 days. Plasma citalopram levels were found to be within the clinical range. 5-HT synthesis was assessed using the decarboxylase inhibition method. Citalopram administration caused a suppression of 5-HT synthesis at all time points. CIT treatment also caused a reduction in forebrain 5-HIAA content. Following chronic CIT treatment, forebrain 5-HT stores were more sensitive to the depleting effects of acute decarboxylase inhibition. CONCLUSIONS/SIGNIFICANCE:Taken together, these results demonstrate that chronic citalopram administration causes a sustained suppression of serotonin synthesis in the mouse forebrain. Furthermore, our results indicate that chronic 5-HT reuptake inhibition renders 5-HT brain stores more sensitive to alterations in serotonin synthesis. These results suggest that the regulation of 5-HT synthesis warrants consideration in efforts to develop novel antidepressant strategies

In vivo actions of the selective 5-HT1A receptor agonist BAY x 3702 on serotonergic cell firing and release

We investigated the effects of the novel 5-HT1A receptor agonist BAY x 3702 on the serotonergic function in rat brain using single unit recordings in the dorsal raphe nucleus (DR) of anesthetized rats and in vivo microdialysis in freely moving rats. The administration of BAY x 3702 (0.25-4 microg/kg i.v.) suppressed the firing activity of 5-HT neurones. This effect was antagonized by a low dose of the selective 5-HT1A receptor antagonist WAY 100635 (5 microg/kg i.v.). In microdialysis experiments, BAY x 3702 (10-100 microg/ kg s.c.) reduced dose-dependently the 5-HT output in the dorsal and median raphe (MnR) nucleus, dorsal hippocampus (DHPC) and medial prefrontal cortex (mPFC) in a regionally selective manner. Maximal effects were observed in the MnR and mPFC, with reductions to approximately 15% of baseline at a dose of 0.1 mg/kg s.c. The decrease in 5-HT output produced in the DR and DHPC was more moderate, to 45% of baseline at 0.1 mg/kg s.c. BAY x 3702. WAY 100635 (0.3 mg/kg s.c.) completely antagonized the effect of BAY x 3702 (30 microg/kg s.c.). The application of BAY x 3702 in the DR (1-100 microM) reduced the local 5-HT output to 25% of baseline. In rats implanted with two dialysis probes (in DR and mPFC) the application of BAY x 3702 (30 microM) in the DR reduced the 5-HT output in the DR and that in mPFC. These effects were significantly antagonized by the co-perfusion of WAY 100635 (100 microM) in the DR. Overall, these results indicate that the systemic administration of BAY x 3702 reduces the 5-HT release with high potency through the activation of midbrain 5-HT1A receptors.Work supported by grants from BAYER S.A. and the Fondo de Investigación Sanitaria (FIS 98/0697). O. Berton was recipient of a postdoctoral fellowship from INSERM (France)Peer reviewe

Eye-Gaze Activity in Crowds: Impact of Virtual Reality and Density

International audienc