Rôle(s) des motivations naturelles dans la prise décision (bases neurobiologiques et comportementales)

La prise de décision est un processus indispensable et vital pour les mammifères. Elle permet à l individu de s adapter aux changements qui s opèrent dans son environnement et résulte de l intégration d informations sensorielles, émotionnelles, motivationnelles et exécutives (qui peuvent être internes ou externes à l individu). Des études, à la fois chez le sujet humain (sujet sain, patients cérébrolésés ou atteints de pathologies psychiatriques), et sur les modèles animaux singe, rats ou souris, ont permis d identifier le cortex préfrontal comme acteur crucial dans ces processus exécutifs complexes. La mise en place au sein de notre laboratoire d un test d interaction sociale permettant de générer des prises de décision rapides et adaptées en présence d un congénère nouveau, nous a permis d étudier les bases neurobiologiques et comportementales sous-jacentes à la prise de décision et à la flexibilité comportementale. Il est connu que les rongeurs émettent des USVs dont le rôle et les mécanismes motivationnels et/ou émotionnels restent largement inconnus à ce jour. Mon travail de thèse repose principalement sur l identification des acteurs cérébraux de cette interaction sociale, et sur le rôle putatif des USVs. D autre part, je me suis employé à comprendre comment les motivations naturelles (telles que la nourriture, l exploration d objet ou de l environnement, et l interaction avec un congénère) sont intégrées au canevas de prise de décision et comment elles l influencent.Dans un premier temps, en utilisant des procédures d imagerie cellulaire basée sur l expression de gènes précoces (c-fos), et ce, à la fois chez des animaux contrôles et chez des animaux présentant des troubles des comportements sociaux (b2KO), nous avons pu mettre en évidence l implication différentielle de sous-parties du cortex préfrontal chez la souris. Par la suite, la mise en place d un logiciel spécifique d analyse, ainsi que la modulation de l état de motivation de l animal lors de la tâche d interaction sociale, nous a permis de mieux comprendre l établissement de comportements adaptés lors de l interaction sociale. Pour finir, en variant les contextes comportementaux, nous avons montré qu il existe une relation étroite entre état émotionnel et motivationnel de l animal et émission d USVs. Notamment, les USVs semblent porter une information spécifique lors de l interaction sociale qui reste encore largement à déterminer.Decision-making is one of the most essential process for mammals. It allows the individual to adapt to environmental changes by the integration of sensory, emotional, motivational and executive information. Numerous studies, in human subject (healthy or not), and on animal models like monkey, rats or mice, have allowed the identification of a major actor in these complex processes: the prefrontal cortex. In our laboratory, we set up a new test, called the social interaction task -SIT-, to generate quick and adapted decision-making in presence of a new congener. This task was used to dissect neural and behavioral bases underlying decision-making and behavioral flexibility during social interaction. It is well known now that rodents emit ultrasonic vocalizations -USVs-, of which roles and mechanisms (motivational or emotional) remain largely unknown. My work was devoted to the identification of brain structures that allow flexible social interactions, and to the unraveling of the putative role(s) of USVs during SIT. I also tried to understand how natural motivations (like social interaction, exploration, and food consumption) take part in the decision-making process.First, by using cellular imaging procedure based on the expression of immediate early genes (c-fos): we were able to highlight the differential involvement of sub-areas of the prefrontal cortex in mice. Subsequently, the development of a new specific software, and the ability to modulate the motivational state of the animal, enabled us to understand better the establishment of adapted behaviors during the SIT. Finally, by varying behavioral contexts, we found a tight relationship between emotional/motivational states and USVs emissions. Notably, USVs appear to carry specific information in social interaction, and this point largely remains to be determined.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

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

Roles of natural motivations in decision-making : neurobiological and behavioral bases

La prise de décision est un processus indispensable et vital pour les mammifères. Elle permet à l’individu de s’adapter aux changements qui s’opèrent dans son environnement et résulte de l’intégration d’informations sensorielles, émotionnelles, motivationnelles et exécutives (qui peuvent être internes ou externes à l’individu). Des études, à la fois chez le sujet humain (sujet sain, patients cérébrolésés ou atteints de pathologies psychiatriques), et sur les modèles animaux singe, rats ou souris, ont permis d’identifier le cortex préfrontal comme acteur crucial dans ces processus exécutifs complexes. La mise en place au sein de notre laboratoire d’un test d’interaction sociale permettant de générer des prises de décision rapides et adaptées en présence d’un congénère nouveau, nous a permis d’étudier les bases neurobiologiques et comportementales sous-jacentes à la prise de décision et à la flexibilité comportementale. Il est connu que les rongeurs émettent des USVs dont le rôle et les mécanismes motivationnels et/ou émotionnels restent largement inconnus à ce jour. Mon travail de thèse repose principalement sur l’identification des acteurs cérébraux de cette interaction sociale, et sur le rôle putatif des USVs. D’autre part, je me suis employé à comprendre comment les motivations naturelles (telles que la nourriture, l’exploration d’objet ou de l’environnement, et l’interaction avec un congénère) sont intégrées au canevas de prise de décision et comment elles l’influencent.Dans un premier temps, en utilisant des procédures d’imagerie cellulaire basée sur l’expression de gènes précoces (c-fos), et ce, à la fois chez des animaux contrôles et chez des animaux présentant des troubles des comportements sociaux (β2KO), nous avons pu mettre en évidence l’implication différentielle de sous-parties du cortex préfrontal chez la souris. Par la suite, la mise en place d’un logiciel spécifique d’analyse, ainsi que la modulation de l’état de motivation de l’animal lors de la tâche d’interaction sociale, nous a permis de mieux comprendre l’établissement de comportements adaptés lors de l’interaction sociale. Pour finir, en variant les contextes comportementaux, nous avons montré qu’il existe une relation étroite entre état émotionnel et motivationnel de l’animal et émission d’USVs. Notamment, les USVs semblent porter une information spécifique lors de l’interaction sociale qui reste encore largement à déterminer.Decision-making is one of the most essential process for mammals. It allows the individual to adapt to environmental changes by the integration of sensory, emotional, motivational and executive information. Numerous studies, in human subject (healthy or not), and on animal models like monkey, rats or mice, have allowed the identification of a major actor in these complex processes: the prefrontal cortex. In our laboratory, we set up a new test, called the social interaction task -SIT-, to generate quick and adapted decision-making in presence of a new congener. This task was used to dissect neural and behavioral bases underlying decision-making and behavioral flexibility during social interaction. It is well known now that rodents emit ultrasonic vocalizations -USVs-, of which roles and mechanisms (motivational or emotional) remain largely unknown. My work was devoted to the identification of brain structures that allow flexible social interactions, and to the unraveling of the putative role(s) of USVs during SIT. I also tried to understand how natural motivations (like social interaction, exploration, and food consumption) take part in the decision-making process.First, by using cellular imaging procedure based on the expression of immediate early genes (c-fos): we were able to highlight the differential involvement of sub-areas of the prefrontal cortex in mice. Subsequently, the development of a new specific software, and the ability to modulate the motivational state of the animal, enabled us to understand better the establishment of adapted behaviors during the SIT. Finally, by varying behavioral contexts, we found a tight relationship between emotional/motivational states and USVs emissions. Notably, USVs appear to carry specific information in social interaction, and this point largely remains to be determined

Rôle(s) des motivations naturelles dans la prise décision : bases neurobiologiques et comportementales

Decision-making is one of the most essential process for mammals. It allows the individual to adapt to environmental changes by the integration of sensory, emotional, motivational and executive information. Numerous studies, in human subject (healthy or not), and on animal models like monkey, rats or mice, have allowed the identification of a major actor in these complex processes: the prefrontal cortex. In our laboratory, we set up a new test, called the social interaction task -SIT-, to generate quick and adapted decision-making in presence of a new congener. This task was used to dissect neural and behavioral bases underlying decision-making and behavioral flexibility during social interaction. It is well known now that rodents emit ultrasonic vocalizations -USVs-, of which roles and mechanisms (motivational or emotional) remain largely unknown. My work was devoted to the identification of brain structures that allow flexible social interactions, and to the unraveling of the putative role(s) of USVs during SIT. I also tried to understand how natural motivations (like social interaction, exploration, and food consumption) take part in the decision-making process.First, by using cellular imaging procedure based on the expression of immediate early genes (c-fos): we were able to highlight the differential involvement of sub-areas of the prefrontal cortex in mice. Subsequently, the development of a new specific software, and the ability to modulate the motivational state of the animal, enabled us to understand better the establishment of adapted behaviors during the SIT. Finally, by varying behavioral contexts, we found a tight relationship between emotional/motivational states and USVs emissions. Notably, USVs appear to carry specific information in social interaction, and this point largely remains to be determined.La prise de décision est un processus indispensable et vital pour les mammifères. Elle permet à l’individu de s’adapter aux changements qui s’opèrent dans son environnement et résulte de l’intégration d’informations sensorielles, émotionnelles, motivationnelles et exécutives (qui peuvent être internes ou externes à l’individu). Des études, à la fois chez le sujet humain (sujet sain, patients cérébrolésés ou atteints de pathologies psychiatriques), et sur les modèles animaux singe, rats ou souris, ont permis d’identifier le cortex préfrontal comme acteur crucial dans ces processus exécutifs complexes. La mise en place au sein de notre laboratoire d’un test d’interaction sociale permettant de générer des prises de décision rapides et adaptées en présence d’un congénère nouveau, nous a permis d’étudier les bases neurobiologiques et comportementales sous-jacentes à la prise de décision et à la flexibilité comportementale. Il est connu que les rongeurs émettent des USVs dont le rôle et les mécanismes motivationnels et/ou émotionnels restent largement inconnus à ce jour. Mon travail de thèse repose principalement sur l’identification des acteurs cérébraux de cette interaction sociale, et sur le rôle putatif des USVs. D’autre part, je me suis employé à comprendre comment les motivations naturelles (telles que la nourriture, l’exploration d’objet ou de l’environnement, et l’interaction avec un congénère) sont intégrées au canevas de prise de décision et comment elles l’influencent.Dans un premier temps, en utilisant des procédures d’imagerie cellulaire basée sur l’expression de gènes précoces (c-fos), et ce, à la fois chez des animaux contrôles et chez des animaux présentant des troubles des comportements sociaux (β2KO), nous avons pu mettre en évidence l’implication différentielle de sous-parties du cortex préfrontal chez la souris. Par la suite, la mise en place d’un logiciel spécifique d’analyse, ainsi que la modulation de l’état de motivation de l’animal lors de la tâche d’interaction sociale, nous a permis de mieux comprendre l’établissement de comportements adaptés lors de l’interaction sociale. Pour finir, en variant les contextes comportementaux, nous avons montré qu’il existe une relation étroite entre état émotionnel et motivationnel de l’animal et émission d’USVs. Notamment, les USVs semblent porter une information spécifique lors de l’interaction sociale qui reste encore largement à déterminer

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

Making choice between competing rewards in uncertain versus safe social environment role of neuronal nicotinic receptors of acetylcholine.

International audienceIn social environments, choosing between multiple rewards is modulated by the uncertainty of the situation. Here, we compared how mice interact with a conspecific and how they use acoustic communication during this interaction in a three chambers task (no social threat was possible) and a Social Interaction Task, SIT (uncertain situation as two mice interact freely). We further manipulated the motivational state of the mice to see how they rank natural rewards such as social contact, food, and novelty seeking. We previously showed that beta2-subunit containing nicotinic receptors-β2(*)nAChRs- are required for establishing reward ranking between social interaction, novelty exploration, and food consumption in social situations with high uncertainty. Knockout mice for β2(*)nAChRs-β2(-/-)mice- exhibit profound impairment in making social flexible choices, as compared to control -WT- mice. Our current data shows that being confronted with a conspecific in a socially safe environment as compared to a more uncertain environment, drastically reduced communication between the two mice, and changed their way to deal with a social conspecific. Furthermore, we demonstrated for the first time, that β2(-/-) mice had the same motivational ranking than WT mice when placed in a socially safe environment. Therefore, β2(*)nAChRs are not necessary for integrating social information or social rewards per se, but are important for making choices, only in a socially uncertain environment. This seems particularly important in the context of Social Neuroscience, as numerous animal models are used to provide novel insights and to test promising novel treatments of human pathologies affecting social and communication processes, among which Autistic spectrum disorders and schizophrenia

A Foxp2 mutation implicated in human speech deficits alters sequencing of ultrasonic vocalizations in adult male mice

Development of proficient spoken language skills is disrupted by mutations of the FOXP2 transcription factor. A heterozygous missense mutation in the KE family causes speech apraxia, involving difficulty producing words with complex learned sequences of syllables. Manipulations in songbirds have helped to elucidate the role of this gene in vocal learning, but findings in non-human mammals have been limited or inconclusive. Here we performed a systematic study of ultrasonic vocalizations (USVs) of adult male mice carrying the KE family mutation. Using novel statistical tools, we found that Foxp2 heterozygous mice did not have detectable changes in USV syllable acoustic structure, but produced shorter sequences and did not shift to more complex syntax in social contexts where wildtype animals did. Heterozygous mice also displayed a shift in the position of their rudimentary laryngeal motor cortex layer-5 neurons. Our findings indicate that although mouse USVs are mostly innate, the underlying contributions of FoxP2 to sequencing of vocalizations are conserved with humans

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

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

Interpretative schema of involvement of calls in motivational/emotionnal process.

<p>Proposition of the link between parameters of the calls and motivational/emotionnal processes in adult male mice.</p