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Reproducible social phenotyping of 5xFAD mice in the Agora maze (Sociobox)
Sheila Sanchez-Garcia1, Bettina Platt1, Gernot Riedel1
1Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Abstract:
Neuropsychiatric (depression, schizophrenia, etc.) and neurological disorders (Alzheimer's disease, AD, Parkinson's 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, PLBWT) 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 5 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.
Insights
The Agora task assesses social novelty preference in mice, crucial for understanding neurological and neuropsychiatric disorders. This robust behavioral paradigm accurately identifies social recognition in mouse models.
Area of Science:
- Neuroscience
- Behavioral Science
- Animal Models
Background:
- Neuropsychiatric and neurological disorders disrupt cognition, particularly social interaction and recognition.
- Developing reliable tools to assess social behavior in mouse models is vital for understanding these impairments.
- Existing methods like the three-chamber test have limitations in the number of social partners and potential for aggression.
Purpose of the Study:
- To validate the Agora task, a novel behavioral paradigm for assessing social novelty preference in mice.
- To evaluate the robustness and reproducibility of the Agora task across different mouse strains and in a disease model.
- To establish a more complex and physiologically relevant method for studying social deficits.
Main Methods:
- The Agora task involves presenting up to five social interaction partners in cubicles, allowing mice to choose interaction partners.
- A discrimination phase introduces a novel mouse (SNew) among familiar ones, with interaction time recorded via video observation.
- Experiments included validation with wild-type mouse strains (C57BL/6J, Balb/c, NMRI, PLBWT) and testing in 5xFAD Alzheimer's disease mice.
Main Results:
- Wild-type mice, except NMRI, demonstrated a preference for social novelty (SNew) by spending more time near their cubicles.
- 5xFAD Alzheimer's mice showed normal social exploration and discrimination at 5 and 8 months of age.
- The Agora task proved robust and reproducible across experiments and cohorts.
Conclusions:
- The Agora task is a validated, robust, and reproducible behavioral paradigm for assessing social novelty preference in mice.
- It offers a more complex and physiologically relevant alternative to existing social interaction tests.
- This paradigm can advance the study of social impairments in neurological and neuropsychiatric disorders.
