Reproducible social phenotyping of 5xFAD mice in the Agora maze (Sociobox)

Abstract

Neuropsychiatric (depression, schizophrenia, etc.) and neurological disorders (Alzheimers disease, AD, Parkinsons disease) are characterized by disruptions in cognition including social interaction and recognition. Developing tools for the assessment of social behaviour in mouse models and its relevance is essential to further advance our understanding of social impairments in these diseases. In the Agora maze for rodents, stranger mice confined into cubicles around the perimeter of the open square mirror the agora (marketplace) in ancient cities. Up to 5 social interaction partners are presented and can be freely selected for interaction (exposure). In the discrimination phase one novel mouse (SNew) is presented while 4 familiar partners remain. Interaction time is recorded via video observation. In Exp 1, we validated the test with different strains of wild-type male mice (C57BL/6J, Balb/c, NMRI) that were able to readily identify SNew and spent significantly more time in zones adjacent to their cubicle; only NMRI mice did not prefer SNew. Exp. 2 explored 5xFAD Alzheimer mice and showed normal exploration and discrimination when aged 6 and 8 months old. Repeat of the experiment in a second cohort confirmed robustness of this phenotype, but also reproducibility of the behavioural paradigm. The Agora task allows semi-automated evaluation of preference for social novelty in a more complex paradigm by expanding the number of social interaction partners from 2 (three-chamber test) to 5 (or more), while still avoiding physical approaches and aggressive episodes. Thus, Agora provides a more physiological behavioural paradigm which is highly robust and reproducible. HighlightsO_LIMore comprehensive behavioural test bed for social recognition C_LIO_LIMale wild-type mice can identify a stranger mouse amongst 5 social interaction partners C_LIO_LINo deficit in amyloid-based Alzheimer model 5xFAD aged 6-8 months. C_LIO_LIRepeat of experiments returned highly robust and reproducible results. C_LI