AUTOMATED ANALYSIS OF RODENT BEHAVIOR USING INTELLIPROFILLER: A POTENTIAL TOOL FOR STUDYING NEURODEVELOPMENTAL DISORDER-LIKE MODEL MICE

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder (NDD) characterized by deficits in social communication and repetitive behaviors. With an increased number of children diagnosed with ASD, the need to understand the mechanisms and symptoms of NDDs is growing to develop effective treatments and interventions. Animal models have been instrumental in studying NDDs, employing classical behavioral paradigms such as the open field test and the social interaction test.

However, obtaining consistent results is still challenging due to the handling effects of experimenters. To address this issue, we have developed a novel system, IntelliProfiler, enabling automated analysis of rodent behavior. IntelliProfiller allows us to analyze the relative distances between individual mice and the travel distances of multiple mice, each embedded with a transponder, without image analysis. The system provides a unique opportunity to evaluate the relative social distance between individuals and groups, which could indicate affinity to others or anxiety in a social environment. Our preliminary analysis using IntelliProfiler revealed pronounced differences in social interaction between wild-type (WT) littermates and a mouse model of ASD (Pax6 heterozygous mutant; Pax6Sey/+). Notably, our previous study did not observe these differences in the three-chamber test (Yoshizaki et al., 2016). Additionally, Pax6Sey/+ female mice exhibited hyperactive behavior and sleep disturbance, suggesting potential comorbidity with attention deficit hyperactivity disorder (ADHD). Our previous research using Pax6rSey2/+ female rats also supports these findings, which exhibited reduced vocal communication and decreased brain volume (Umeda et al., 2010; Hiraoka et al., 2016). Our data suggest that Pax6Sey/+ female mice may serve as a valuable model for studying severe sex-biased ASD-like features, potentially with concomitant ADHD. The application of IntelliProfiller in studying neuropsychiatric behaviors in NDD model mice holds significant promise, offering several advantages over classical behavior analyses. These advantages include 1) the ability to conduct long-term studies of basal activity in a non-contact setting and 2) quantitative analyses of anxiety in social environments using multiple animals.

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