Continuous behavioral phenotyping in socially housed mice using the IntelliCage

Abstract

Introduction – Classical behavioral assays in mice often require repeated handling, short test sessions, social isolation during testing, and sequential assessment of individual animals. These factors can introduce experimenter-associated disturbance and limit the temporal resolution with which behavioral dynamics are observed. Automated home-cage systems provide an alternative approach by enabling standardized, long-term behavioral monitoring under less disruptive conditions. The IntelliCage combines RFID-based individual identification with computer-controlled operant corners, allowing behavioral phenotyping of group-housed mice in a digitally controlled environment.

Description – We used the IntelliCage as a semi-naturalistic platform to assess behavioral dynamics in socially housed mice. Animals freely interacted with operant corners in a self-paced manner, while individual visits, nosepokes, licking behavior, corner preferences, and reward-related actions were recorded continuously. As examples, we present place learning and place reversal experiments probing reward-based spatial memory, as well as stress paradigms assessing depression-like phenotypes through changes in hedonic behavior. These paradigms allow long-term quantification of activity, exploration, reward seeking, spatial learning, behavioral flexibility, and stress-related behavioral changes with minimal experimenter interference. Where appropriate, IntelliCage monitoring can also be combined with defined experimental interventions and cellular readouts within the same longitudinal study design.

Conclusion – The IntelliCage enables behavioral performance to be analyzed as a longitudinal trajectory rather than as a set of isolated test outcomes. By preserving social housing conditions, reducing repeated handling, and recording behavior continuously over days to weeks, automated home-cage systems provide a scalable and refinement-oriented framework for behavioral phenotyping. This approach supports high-throughput testing, facilitates the translation of classical behavioral paradigms into self-paced home-cage protocols, and allows experimentally controlled manipulations to be linked to adaptive behavior under more naturalistic conditions.

Acknowledgement – We especially thank the DZNE Animal Research Facility for their close collaboration, coordination, and continuous support, which made the IntelliCage experiments at our institute possible. We also thank the DZNE Light Microscope Facility for technical support. The stress-related behavioral phenotyping experiments were performed within the NEURON-funded MicroSynDep project and we kindly thank our collaborators: Igor Branchi, Maciej Lalowski, Bozena Kaminska, and Marie-Eve Tremblay.

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