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de Chaumont, F.

Publications and source records attributed to de Chaumont, F..

8 recordsLinked to original sources

Female C57BL/6J mice perform distinctive urination behaviour accompanied by ultrasonic vocalisations sequences with a stereotypic temporal organisation.

Ultrasonic vocalisations (USVs) are largely studied in mice as a marker of social communication. These USVs are usually recorded during short social encounters in unfamiliar test cages. In the present study, we explored how freely interacting pairs of C57BL/6J adult female mice spontaneously use USVs over long-term monitoring. In this situation, we discovered that these mice display a previously undescribed behaviour: they emit specific USV sequences while depositing a large quantity of urine in a corner of the cage. The most striking feature of USVs accompanying this vocalised urination behaviour was the stereotyped duration of the inter-USV intervals. The variability in the frequency of occurrence of this behaviour was important between pairs. Interestingly, when accompanied by the specific USV sequence, urination was correlated with a significant increase in locomotor activity in both the emitter and the cage mate, in contrast with urination without USVs. Altogether, the observation and description of this vocalised urination behaviour argue for exploring mouse vocalisations at the sequence level to understand the USV-behaviours interactions.

animal behavior and cognition↗

Complex social behaviour during an extended period of time in a valproic acid animal model of autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a progressive neurodevelopmental disorder characterized mainly by deficits in social communication and stereotyped and restricted interests. Deficits in social interactions in ASD animal models are generally analysed using the three chambers test paradigm that is simple to implement and use but fails to detect subtle social deficits or complex social behavior on an extended period of time within a group of mice. Here, we set up a novel procedure entitled the Live Mouse Tracker (LMT) that detects a great number of complex social behaviours that we recorded continuously for up to three days in groups of 4 mice. This was performed in the valproic acid (VPA) mouse model where VPA (450 mg/kg) was injected to pregnant females at E12.5. Studies were performed with a special focus on females given that ASD is 3-4 times more diagnosed in males than in females and that several ASD models failed to detect major social deficits in females, contrary to males. Comparisons were made within groups of 4 female animals with same treatment or within groups of different treatments (saline versus VPA). We report that VPA females show several types of social deficits and that are different in nature and magnitude in relation with time (from 1 hour to 3 days). These deficits were also different when VPA mice were tested together compared to when they were mixed with saline treated mice. Indeed, while social behavior was improved in VPA mice with the presence of saline mice that of saline mice was negatively affected by the presence of VPA mice. This study indicates that female VPA mice show several social deficits, contrary to the common knowledge. It further implies that ASD related behavior alters normal behavior in a mixed group of mice.

neuroscience↗

A 16p11.2 deletion mouse model displays quantitatively and qualitatively different behaviours in sociability and social novelty over short- and long-term observation.

BackgroundAutism spectrum disorders affect more than one percent of the population, impairing social communication and increasing stereotyped behaviours. A micro-deletion of the 16p11.2 BP4-BP5 chromosomic region has been identified in one percent of patients also displaying intellectual disabilities. In mouse models generated to understand the mechanisms of this deletion, learning and memory deficits were pervasive in most genetic backgrounds, while social communication deficits were only detected in some models. MethodsBased on previous study (Arbogast et al. 2016 PLoS genetics), we itemized the social deficits in the mouse model of 16p11.2 deletion on a hybrid C57BL/6NxC3H.Pde6b+ genetic background. We examined whether behavioural deficits were visible over long-term observation periods, to parallel everyday-life assessment of patients. We recorded the individual and social behaviours of 16p11.2 Del/+ mice and their wild-type littermates from both sexes in long-term (over two and three consecutive nights) social interactions of familiar mixed-genotype quartets of males and of females, and of same-genotype unfamiliar female pairs. ResultsWe observed that Del/+ mice of both sexes increased significantly their locomotor activity compared to wild-type littermates over long-term monitoring. In the social domain, Del/+ mice of both sexes displayed widespread deficits over long-term monitoring, even more so in males than in females in quartets of familiar individuals. In pairs, significant perturbations of the organisation of the social communication and behaviours appeared in Del/+ females. DiscussionAltogether, this suggests that, over long recording periods, the phenotype of the 16p11.2 Del/+ mice was differently affected in the locomotor activity and the social domains and between the two sexes. These findings confirm the importance of testing models in long-term conditions to provide a comprehensive view of their phenotype that will refine the study of cellular and molecular mechanisms and complement pre-clinical targeted therapeutic trials.

animal behavior and cognition↗

Deep learning-based system for real-time behavior recognition and closed-loop control of behavioral mazes using depth sensing

Robust quantification of animal behavior is fundamental in experimental neuroscience research. Systems providing automated behavioral assessment are an important alternative to manual measurements avoiding problems such as human bias, low reproducibility and high cost. Integrating these tools with closed-loop control systems creates conditions to correlate environment and behavioral expressions effectively, and ultimately explain the neural foundations of behavior. We present an integrated solution for automated behavioral analysis of rodents using deep learning networks on video streams acquired from a depth-sensing camera. The use of depth sensors has notable advantages: tracking/classification performance is improved and independent of animals coat color, and videos can be recorded in dark conditions without affecting animals natural behavior. Convolutional and recurrent layers were combined in deep network architectures, and both spatial and temporal representations were successfully learned for a 4- classes behavior classification task (standstill, walking, rearing and grooming). Integration with Arduino microcontrollers creates an easy-to-use control platform providing low-latency feedback signals based on the deep learning automatic classification of animal behavior. The complete system, combining depth-sensor camera, computer, and Arduino microcontroller, allows simple mapping of input-output control signals using the animals current behavior and position. For example, a feeder can be controlled not by pressing a lever but by the animal behavior itself. An integrated graphical user interface completes a user-friendly and cost-effective solution for animal tracking and behavior classification. This open-software/open-hardware platform can boost the development of customized protocols for automated behavioral research, and support ever more sophisticated, reliable and reproducible behavioral neuroscience experiments.

animal behavior and cognition↗

Excessive self-grooming of Shank3 mutant mice is associated with gene dysregulation and imbalance between the striosome and matrix compartments in the striatum

Autism is characterised by atypical social communication and stereotyped behaviours. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are detected in 1-2% of patients with autism and intellectual disability (ID), but the mechanisms underpinning the symptoms remain largely unknown. Here, we characterised the behaviour of Shank3{Delta}11/{Delta}11 mice from three to twelve months of age. We observed decreased locomotor activity, increased stereotyped self-grooming and modification of socio-sexual interaction compared to wild-type littermates. We then used RNAseq on four brain regions of the same animals to identify differentially expressed genes (DEG). DEGs were identified mainly in the striatum and were associated with synaptic transmission (e.g. Grm2, Dlgap1), G-protein-signalling pathways (e.g. Gnal, Prkcg1, and Camk2g), as well as excitation/inhibition balance (e.g. Gad2). Downregulated and upregulated genes were enriched in the gene clusters of medium-sized spiny neurons expressing the dopamine 1 (D1-MSN) and the dopamine 2 receptor (D2-MSN), respectively. Several DEGs (Cnr1, Gnal1, Gad2, and Drd4) were reported as striosome markers. By studying the distribution of the glutamate decarboxylase GAD65, encoded by Gad2, we showed that the striosome compartment of Shank3{Delta}11/{Delta}11 mice was enlarged and displayed much higher expression of GAD65 compared to wild-type mice. Altogether, these results indicate altered gene expression in the striatum of SHANK3-deficient mice and strongly suggest, for the first time, that the impairment in behaviour of these mice are related to an imbalance striosomes/matrix.

neuroscience↗

Cell Tracking Profiler: a user-driven analysis framework for evaluating 4D live cell imaging data

Accurate measurements of cell morphology and behaviour are fundamentally important for understanding how disease, molecules and drugs affect cell function in vivo. Using muscle stem cell (muSC) responses to injury in zebrafish as our biological paradigm we have established a ground truth for muSC cell behaviour. This revealed that variability in segmentation and tracking algorithms from commonly used programs are error-prone, leading us to develop a fast semi-automated image analysis pipeline that allows user defined parameters for segmentation and correction of cell tracking. Cell Tracking Profiler (CTP) operates through the freely available Icy platform, and allows user-managed cell tracking from 3D time-lapsed datasets to provide measures of cell shape and movement. Using dimensionality reduction methods, multiple correlation and regression analyses we identify myosin II-dependent parameters of muSC behaviour during regeneration. CTP and the associated statistical tools we have developed thus provide a powerful framework for analysing complex cell behaviour in vivo from 4D datasets. SummaryAnalysis of cell shape and movement from 3D time-lapsed datasets is currently very challenging. We therefore designed Cell Tracking Profiler for analysing cell behaviour from complex datasets and demonstrate its effectiveness by analysing stem cell behaviour during muscle regeneration in zebrafish.

cell biology↗

Dlx5 and Dlx6 expression in GABAergic neurons controls behavior, metabolism, healthy aging and lifespan.

Dlx5 and Dlx6 encode two homeobox transcription factors expressed by developing and mature GABAergic interneurons. During development Dlx5/6 are important for the differentiation of Parvalbumin (Pvalb)-expressing neurons. Perinatal lethality of homozygous mice in which Dlx5/6 have been constitutively deleted has, so far, hindered the study of the function of these genes in adult neurons. We first show that Dlx5 and Dlx6 are expressed by all subclasses of adult cortical GABAergic neurons. Then we analyse Vgat{Delta}Dlx5-6 mice in which Dlx5 and Dlx6 are simultaneously inactivated in all GABAergic interneurons. Vgat{Delta}Dlx5-6 mice present a behavioral pattern suggesting reduction of anxiety and obsessive-compulsive activities. They rapidly access and spend more time in the central region of an open field, bury few marbles in the marble burying test and show little interest in nest building. Male and female 20-month-old Vgat{Delta}Dlx5-6 animals have the same size as their normal littermates, but present a 25% body weight reduction associated with a marked decline in white and brown adipose tissue. Remarkably, both Vgat{Delta}Dlx5-6/+ and Vgat{Delta}Dlx5-6 mice present a 33% longer median survival than their control littermates. Hallmarks of biological aging such as motility, adipose deposition and coat conditions are improved in mutant animals. Our data imply that GABAergic interneurons can regulate mammalian healthspan and lifespan through Dlx5/6-dependent mechanisms. Understanding these regulations can be an entry point to unravel the processes through which the brain affects body homeostasis and, ultimately, longevity and healthy aging.\n\nSIGNIFICANCE STATEMENTDlx5 and Dlx6 are transcription factors controlling several developmental processes, including GABAergic neuronal migration and differentiation. To study their function in adult brain, we selectively inactivated both genes in GABAergic interneurons (Vgat{Delta}Dlx5-6 mice). Mutant mice have reduced anxiety-like and obsessive-compulsive behaviors. Interestingly, Vgat{Delta}Dlx5-6 mice have a 25% body weight reduction and about 70% less white and brown adipose tissue; their general health status is excellent. Vgat{Delta}Dlx5-6 mice have a median survival about 33% longer than their control littermates and hallmarks of biological aging are improved. Dlx5/6-dependent regulations in GABAergic neurons could be an entry point to understand how the brain determines the psychophysiological status of the body and, ultimately, longevity and healthy aging.

physiology↗

Live Mouse Tracker: real-time behavioral analysis of groups of mice

Preclinical studies of psychiatric disorders require the use of animal models to investigate the impact of environmental factors or genetic mutations on complex traits such as decision-making and social interactions. Here, we present a real-time method for behavior analysis of mice housed in groups that couples computer vision, machine learning and Triggered-RFID identification to track and monitor animals over several days in enriched environments. The system extracts a thorough list of individual and collective behavioral traits and provides a unique phenotypic profile for each animal. On mouse models, we study the impact of mutations of genes Shank2 and Shank3 involved in autism. Characterization and integration of data from behavioral profiles of mutated female mice reveals distinctive activity levels and involvement in complex social configuration.

animal behavior and cognition↗