A novel social proximity test suggests patterns of social avoidance and gaze aversion-like behavior in BTBR T+ tf/J mice

Abstract

The BTBR T+tf/J (BTBR) inbred mouse strain displays a low sociability phenotype relevant to the first diagnostic symptom of autism, deficits in reciprocal social interactions. Previous studies have shown that BTBR mice exhibit reduced social approach, juvenile play, and interactive behaviors. The present study evaluated the behavior of the BTBR and C57BL/6J (B6) strains in social proximity. Subjects were closely confined and tested in four experimental conditions: same strain male pairs (Experiment 1); different strain male pairs (Experiment 2); same strain male pairs and female pairs (Experiment 3); and same strain male pairs treated with an anxiolytic (Experiment 4). Results showed that BTBR mice displayed decreased nose tip-to-nose tip, nose-to-head and upright behaviors and increased nose-to-anogenital, crawl under and crawl over behaviors. These results demonstrated avoidance of reciprocal frontal orientations in the BTBR, providing a parallel to gaze aversion, a fundamental predictor of autism. For comparative purposes, Experiment 3 assessed male and female mice in a three-chamber social approach test and in the social proximity test. Results from the three-chamber test showed that male B6 and female BTBR displayed a preference for the sex and strain matched conspecific stimulus, while female B6 and male BTBR did not. Although there was no significant interaction between sex and strain in the social proximity test, a significant main effect of sex indicated that female mice displayed higher levels of nose tip-to-nose tip contacts and lower levels of anogenital investigation (nose-to-anogenital) in comparison to male mice, all together suggesting different motivations for sociability in males and females. Systemic administration of the anxiolytic, diazepam, decreased the frequency of two behaviors associated with anxiety and defensiveness, upright and jump escape, as well as crawl under behavior. This result suggests that crawl under behavior, observed at high levels in BTBR mice, is elicited by the aversiveness of social proximity, and possibly serves to avoid reciprocal frontal orientations with other mice.

Mecp2 Truncation in Male Mice Promotes Affiliative Social Behavior

“…The social proximity task was designed to differentiate close-quarter differences in social interactions (Defensor et al 2011). In the current study, Mecp2 308/Y mice showed elevated frequencies and/or durations of crawl-under, crawl-over behaviors, and nose-to-face investigation.…”

“…Social proximity testing was conducted in a clear rectangular chamber (7 ×14 × 30 cm H) constructed of acrylic plastic according to previously reported parameters (Defensor et al 2011). The dimensions of this arena were identical to that used for analyses of individual autogrooming behavior.…”

“…This permitted the assessment of adult mice prior to the onset of severe sleep, neurological, and musculo-skeletal deficits. The tests used were designed to reveal subtle and overt distinctions in social interactions and repetitive behavior, which have proven to be relevant variables for mouse models of neurodevelopmental disorders (Arakawa et al 2007; Defensor et al 2011; Moy et al 2004; Pearson et al 2010, 2011; Pobbe et al 2010). …”

Sex differences in animal models of psychiatric disorders

“…In particular, male BTBR mice show social deficits that are not evident in female BTBR mice (Defensor et al, 2011). However, both male and female juvenile and adult BTBR mice exhibited deficits in social interactions when paired with novel partners of different strains.…”

Co-learning facilitates memory in mice: A new avenue in social neuroscience

“…BTBR T þ tf/J (BTBR) is a reliable mouse model of autism with deficient social affiliation, social transmission of food preference, ultrasonic vocalizations in response to social cues, high repetitive self-grooming and gaze aversion-like behaviors (McFarlane et al, 2008;Scattoni et al, 2008Scattoni et al, , 2011Defensor et al, 2011). In parallel, BTBR mice also show a severe contextual fear memory deficit (MacPherson et al, 2008).…”