Adult Male Mice Emit Context-Specific Ultrasonic Vocalizations That Are Modulated by Prior Isolation or Group Rearing Environment

Social interactions in mice are frequently analysed in genetically modified strains in order to get insight of disorders affecting social interactions such as autism spectrum disorders. Different types of social interactions have been described, mostly between females and pups, and between adult males and females. However, we recently showed that social interactions between adult males could also encompass cognitive and motivational features. During social interactions, rodents emit ultrasonic vocalizations (USVs), but it remains unknown if call types are differently used depending of the context and if they are correlated with motivational state. Here, we recorded the calls of adult C57BL/6J male mice in various behavioral conditions, such as social interaction, novelty exploration and restraint stress. We introduced a modulator for the motivational state by comparing males maintained in isolation and males maintained in groups before the experiments. Male mice uttered USVs in all social and non-social situations, and even in a stressful restraint context. They nevertheless emitted the most important number of calls with the largest diversity of call types in social interactions, particularly when showing a high motivation for social contact. For mice maintained in social isolation, the number of calls recorded was positively correlated with the duration of social contacts, and most calls were uttered during contacts between the two mice. This correlation was not observed in mice maintained in groups. These results open the way for a deeper understanding and characterization of acoustic signals associated with social interactions. They can also help evaluating the role of motivational states in the emission of acoustic signals

L'inhibition de l'époxyde hydrolase soluble‎ : un futur traitement de l'atteinte vasculaire cutanée de la sclérodermie

La sclérodermie est une pathologie auto-immune, touchant majoritairement les femmes. Ses symptômes les plus fréquents sont cutanés. La peau apparaît comme épaissie, dure, ce qui a d'ailleurs donné son nom à cette maladie. En cas de sclérodermie systémique, les atteintes au niveau des organes internes peuvent être gravissimes et le pronostic vital du patient peut être engagé. Les traitements actuels ne permettent que de réduire les symptômes, au mieux de stabiliser l'évolution de la maladie. Des études cliniques sont en cours afin de traiter la sclérodermie par anticorps monoclonaux. Parmi les atteintes fréquentes de la sclérodermie, on retrouve les atteintes vasculaires périphériques, ayant des retentissements au niveau cutané. Les EETs, des phospholipides ayant un rôle vasodilatateur et protecteur au niveau vasculaire, sont naturellement présents dans l'organisme et dégradés par une enzyme nommée l'époxyde hydrolase soluble, ou sEH. Le fait d'inhiber cette enzyme permet de maintenir une concentration en EETs suffisamment importante pour que des effets bénéfiques soient constatables. Des études cliniques sont par ailleurs en cours pour évaluer l'intérêt des inhibiteurs de sEH

Interaction entre prise de décision et gestion des motivations chez la souris (bases neurobiologiques et comportementales)

La flexibilité comportementale se définit par la capacité à prendre une décision adaptée en fonction de ses motivations internes et des changements qui peuvent survenir dans l environnement. L objectif de cette thèse est d explorer dans le contexte incertain d une tâche d interaction sociale, les processus comportementaux et neurobiologiques à la base des prises de décision flexibles chez la souris. L utilisation de souris mutantes nulles pour la sous-unité b2 des récepteurs nicotiniques à l acétylcholine et la réexpression par lentivirus de cette sous-unité dans le cortex préfrontal nous ont permis de démontrer son rôle crucial dans la flexibilité des comportements lors de situations présentant un conflit entre plusieurs motivations. Nous avons également, par des expériences de lésion et d imagerie régionale d'expression de la protéine c-Fos, précisé l importance de l aire prélimbique du cortex préfrontal dans la prise de décision adaptée. Par ailleurs, nous avons constaté que les souris impulsives montrent une atteinte de la flexibilité des comportements lorsqu elles doivent opérer un choix entre exploration, interaction sociale et consommation de nourriture, trois motivations naturelles fondamentales. Enfin, l analyse des vocalisations ultrasoniques dans différents contextes comportementaux a mis en évidence que le nombre, le type et les propriétés acoustiques des vocalisations reflètent à la fois l'état émotionnel et motivationnel des souris. L ensemble des travaux, tant comportementaux que neurobiologiques, a, en outre, conduit au développement et à la validation d outils appropriés à l étude de l impulsivité motrice et des interactions sociales chez la sourisPARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF

Beta 2-containing neuronal nicotinic receptors as major actors in the flexible choice between conflicting motivations.

International audienceBeside a critical role in nicotine addiction, the role of nicotinic receptors in cognitive or emotional processes remains difficult to elucidate, mostly because of a lack of specificity of compounds and because they up or down regulate easily. Using knockout mice may be one key to elucidate the role of nicotinic receptors stimulated by their endogenous ligand acetylcholine. We and others have previously explored the behaviour of mice knockout for the beta2-subunit containing nicotinic receptor - β2*nAChRs - β2(-/-) mice. These mice exhibit a particular kind of hyperactive locomotion, with profound deficits in cognitive and social interaction tasks, only when they have to show flexible choices. We wonder here whether the latter is due to a lack of motor control - i.e. motor impulsivity, a lack of estimation of reward value - i.e. cognitive impulsivity, and/or a lack of appropriate ranking or choice between different motivations. We designed behavioural tasks allowing the study of these distinct processes in mice. Our current results highlight the important role of β2*nAChRs in flexible behaviours in conflicting situations, such as social contact, spatial exploration and food consumption. They also show that the cognitive deficits exhibited by β2(-/-) mice cannot be explained by impaired inhibitory behaviours. Although social cognition is considerably enriched in humans as compared to rodents, we provide here novel data for the neurobiology of flexible social behaviours that could ultimately be useful for humans. Indeed, the ability to show flexible behaviours and to display adapted social interactions is profoundly impaired in a myriad of psychiatric disorders

Prefrontal nicotinic receptors control novel social interaction between mice.

International audienceSocial behavior is a defining mammalian feature that integrates emotional and motivational processes with external rewarding stimuli. It is thus an appropriate readout for complex behaviors, yet its neuronal and molecular bases remain poorly understood. In this study, we investigated the role of the mouse prefrontal area, particularly the involvement of β2-subunit nicotinic receptors (β2*-nAChRs) in a paradigm of social behavior with concurrent motivations. We previously observed that mice lacking β2*-nAChRs (β2(-/-)) display increased time in social contact and exaggerated approach movements toward the novel conspecific. Here, combining behavioral analysis, localized brain lesions, and lentiviral gene rescue, we found that c-Fos expression is specifically activated in the prelimbic (PrL) area of the prefrontal cortex (PFC) of mice exposed to a novel conspecific; lesions of the PrL area in wild-type mice produce the same social pattern as in β2(-/-) mice; and virally mediated reexpression of the β2-subunit in the PrL area of β2(-/-) mice rescues behavioral components in the social interaction task up to normal levels. Together, these data reveal that social interactions particularly mobilize the PrL area of the mouse PFC and that the presence of functional PrL β2*-nAChRs is necessary for this integrated behavior to emerge

Computerized video analysis of social interactions in mice.

International audienceThe study of social interactions in mice is used as a model for normal and pathological cognitive and emotional processes. But extracting comprehensive behavioral information from videos of interacting mice is still a challenge. We describe a computerized method and software, MiceProfiler, that uses geometrical primitives to model and track two mice without requiring any specific tagging. The program monitors a comprehensive repertoire of behavioral states and their temporal evolution, allowing the identification of key elements that trigger social contact. Using MiceProfiler we studied the role of neuronal nicotinic receptors in the establishment of social interactions and risk-prone postures. We found that the duration and type of social interactions with a conspecific evolves differently over time in mice lacking neuronal nicotinic receptors (Chrnb2-/-, here called β2(-/-)), compared to C57BL/6J mice, and identified a new type of coordinated posture, called back-to-back posture, that we rarely observed in β2(-/-) mice

Number of calls and vocal repertoire uttered in five behavioral contexts.

<p>A- Calls were recorded during social interaction task, novelty exploration, and restraint stress and analyzed off line. B- Total number of calls emitted in 4 minutes: SIT-isolated (n = 17), SIT-grouped (n = 8), EXPLO-isolated (n = 15), EXPLO-grouped (n = 8) and RESTRAINT (n = 16). C- Distribution and <b>s</b>pectrograms of the ten call types typically emitted by adult male mice. Data not shown, proportion of “other” calls: 1.4±0.8% in SIT-isolated, 4.5±1.3% in SIT-grouped, 9.5±4.1% in EXPLO-grouped, 3.1±1.3% in EXPLO-isolated and 16.3±3.1% in Restraint stress. (Time and frequency criterion were used to distinguish these categories, <i>see methods</i>). Data are presented as means ± SE. *: p<0.005; **: p<0.0001 for chi-square and Mann-Whitney paired comparisons.</p

Acoustic characteristics of calls emitted in five behavioral contexts.

<p>A- Calls durations in all conditions. B- Calls durations for all call types in all conditions. C- Frequency features (“min”, “max”, “start” and “end” frequencies) of calls in all conditions. Data are presented as means ± SE. *: p<0.005; **: p<0.0001 for Mann-Whitney paired comparison.</p

Correlation between behavioral contexts and calls emission.

<p>Correlation between the number of calls of the 3 main categories (“Short”, “Jump” and “Upward”) and duration of contact during social interaction in isolated or non-isolated mice. **: p = 0.005 for Spearman rank correlation test and NS: p>0.05.</p