Cross-site reproducibility of social deficits in group-housed BTBR mice using automated longitudinal behavioural monitoring

Social withdrawal is associated with a variety of neuropsychiatric disorders, including neurodevelopmental disorders. Rodent studies provide the opportunity to study neurobiological mechanisms underlying social withdrawal, however, homologous paradigms to increase translatability of social behaviour between human and animal observation are needed. Standard behavioural rodent assays have limited ethological validity in terms of number of interaction partners, type of behaviour, duration of observation and environmental conditions. In addition, reproducibility of behavioural findings in rodents is further limited by manual and subjective behavioural scoring. Using a newly developed automated tracking tool for longitudinal monitoring of freely moving mice, we assessed social behaviours (approach, sniff, follow and leave) over seven consecutive days in colonies of BTBR and of C57BL/6J mice in two independent laboratories. Results from both laboratories confirmed previous findings of reduced social interaction in BTBR mice revealing a high level of reproducibility for this mouse phenotype using longitudinal colony assessments. In addition, we showed that detector settings contribute to laboratory specific findings as part of the behavioural data analysis procedure. Our cross-site study demonstrates reproducibility and robustness of reduced social interaction in BTBR mice using automated analysis in an ethologically relevant context

The reverse translation of a quantitative neuropsychiatric framework into preclinical studies:Focus on social interaction and behavior

Following the Research Domain Criteria (RDoC) concept, major brain circuits are conserved in evolution and malfunctioning of a brain circuit will lead to specific behavioral symptoms. Reverse translation of patient-based findings from Alzheimer’s disease (AD), schizophrenia (SZ) and major depression (MD) patients to preclinical models accordingly can be a starting point for developing a deeper understanding of the functional circuit biology and contribute to the validation of new hypotheses for therapeutic intervention in patients. In the context of the EU funded PRISM project, a preclinical test battery of tasks has been selected and aligned with the clinical test battery. It allows for assessment of social functioning, sensory processing, attention and working memory and is designed for validation of biological substrates from human molecular landscaping of social withdrawal. This review will broadly summarize the available literature on tasks for studying social behavior in rodents and outline the development of a preclinical test battery for the PRISM project by reverse translation

RFID-supported video tracking for automated analysis of social behaviour in groups of mice

BACKGROUND: Deficits in social behaviour, e.g. social withdrawal, appear as an early sign of many neuropsychiatric disorders. Investigation of the biological basis of social withdrawal and development of new targets for treatment requires reliable quantification methods of social behaviour. NEW METHOD: In order to study behavioural deficits in preclinical rodent models, we developed a tracking and analysis tool for behavioural observations in groups of mice. RFID-Assisted SocialScan is based on video tracking supported by radio-frequency identification (RFID). For this purpose, mice were labelled with RFID tags providing unique animal identity and location in the arena. An integrated software package enables automatic detection of predefined behavioural events, which are extracted from video recordings. We designed a social arena that can be flexibly adapted for various behavioural experiments. RESULTS: We demonstrate the utility of our newly developed tracking tool by monitoring colonies of C57BL/6 J mice. We assessed social (approach, contact, follow, leave) and locomotor activities over multiple days. COMPARISON WITH OTHER EXISTING METHODS: RFID-Assisted SocialScan is an automated tracking and analysis tool for long-term behavioural observations of multiple freely moving mice housed in ethologically relevant environment. CONCLUSIONS: Here, we demonstrate the performance of a newly developed behavioural tracking system that can be used for long-term translational studies of social behaviour in groups of freely moving mice