Influence of Partner Cues On Social Behaviors in the BTBR Mouse Model of Autism

Background: BTBR T+ tf/J (BTBR) is an inbred strain that exhibits low sociability in our three-chambered social approach task and low reciprocal social interactions in a neutral arena (Bolivar et al., 2007; McFarlane et al., 2008). Previous findings demonstrated that the social deficits in BTBR are not attributable to postnatal maternal care or to circadian phase, and their absence of corpus callosum is unlikely to be the primary cause (Yang et al., 2009). 

Objectives: The present study tests specific features of a novel social animal that may deter BTBR from approaching other mice. Experiment 1 compares social approach behaviors elicited by a salient social olfactory cue vs. a live behaving mouse.  Experiment 2 compares the subject’s social scores when the partner is a highly social C57BL/6J (B6) which frequently initiate social interactions, versus when the partner is a low sociability BTBR.
Methods: Experiment 1: To test for social approach behaviors towards a live animal, a novel mouse was placed under an inverted wire cup located in one side chambers, and an control empty cup was placed in the other side chamber. To test for approach behaviors elicited by social olfactory cues, soiled bedding obtained from unfamiliar cages of group-housed mice was placed under the cup in one side chamber, and clean bedding was placed under the control cup in the other side chamber.
Experiment 2: Social interactions in three types of social pairs were tested:  a) pairs of two B6, b) pairs of two BTBR, and c) pairs of one B6 and one BTBR. A juvenile cohort was tested on postnatal day 21 and an adult cohort was tested between 8-16 weeks of age. The same testing procedure was used for the juvenile and the adult test. After a 1 hour isolation period, two age- and sex-matched non-littermates were simultaneously placed in a neutral arena and their interactions were videotaped for 10 min.

Results: Experiment 1 revealed that BTBR displayed strong approach behaviors towards olfactory social cues, but low approach to a live, awake novel mouse. A previous report showed that B6 mice exhibit high social approach towards soiled nesting material from novel mice (Ryan et al., 2008).  In our study, BTBR spent as much time with the novel home cage odors as did B6 in the Ryan study. Experiment 2 found that BTBR exhibited low reciprocal social interactions when paired with either highly social B6 partners or low sociability BTBR partners, generally do not reciprocate when approached or solicited.  In contrast, B6 exhibited high sociability to both B6 and BTBR partners, maintaining high levels of social interests even when the BTBR did not reciprocate.  Similar results were obtained from juvenile and adult pairs, and from male pairs and female pairs.

Conclusions: Our results support the interpretation that BTBR are interested in social olfactory cues, but avoid contact with novel mice, independent of any strain-specific behavioral or olfactory cues emitted by the novel mice. These findings might have face validity to the description that some autistic individuals recognize components of social cues, but avoid or respond inappropriately to direct social contact.