Deep behavioral phenotyping of mouse autism models using open-field behavior

Abstract

AO_SCPLOWBSTRACTC_SCPLOWAutism is noted for both its genotypic and phenotypic diversity. Repetitive action, resistance to environmental change, and motor disruptions vary from individual to individual. In animal models, conventional behavioral phenotyping captures such fine-scale variations incompletely. Here we use advances in computer vision and deep learning to develop a framework for characterizing mouse behavior on multiple time scales using a single popular behavioral assay, the open field test. We observed male and female C57BL/6J mice to develop a dynamic baseline of adaptive behavior over multiple days. We then examined two rodent models of autism, a cerebellum-specific model, L7-Tsc1, and a whole-brain knockout model, Cntnap2. Both Cntnap2 knockout and L7-Tsc1 mutants showed forelimb lag during gait. L7-Tsc1 mutants showed complex defects in multi-day adaptation, lacking the tendency of wild-type mice to spend progressively more time in corners of the arena. In L7-Tsc1 mutant mice, failure-to-adapt took the form of maintained ambling, turning, and locomotion, and an overall decrease in grooming. Adaptation in Cntnap2 knockout mice more broadly resembled that of wild-type. L7-Tsc1 mutant and Cntnap2 knockout mouse models showed different patterns of behavioral state occupancy. Our automated pipeline for deep phenotyping successfully captures model-specific deviations in adaptation and movement as well as differences in the detailed structure of behavioral dynamics.