Social Choice in the BTBR Mouse Model of ASD

Background: The social approach test examines sociability in mice that have a choice between interacting with a stranger mouse or a novel object. Most mice spend more time with the stranger mouse which is interpreted as normal sociability, for example the C57BL/6J (B6) mice. The BTBR T+tj/J (BTBR) strain of mice do not spend more time with the stranger mouse, which appears to be independent of partner strain (Yang et al. 2012 Physiol & Behavior 107:649).  There is evidence that olfactory cues are sufficient to provide a social cue in this test in the B6 mice (Ryan et al. 2008 Beh Brain Res 193:235).  It is unclear if the BTBR mice will prefer to spend time with more social (B6) mice or the less social (BTBR) mice or what aspects of the stranger mice determine preference in the BTBR mice.

Objectives:  To test the social preference of these different strains of mice, the subject mouse given a choice between two stranger mice, one with “normal” (see above) sociability or one with lower sociability (BTBR).  The preference of the subject mouse for a stranger mouse or dirty bedding from the stranger mouse cage was also tested.

Methods: The three chambered social approach apparatus was used very similarly to previous studies. The modifications were during the sociability phase. For the first experiment, there was a mouse placed in each side chamber – a B6 on one side and a BTBR mouse on the other counterbalanced across subject mice. For the second experiment, each side chamber contained either a stranger mouse or bedding from the stranger mouse cage, counterbalanced across subject mice. All stranger mice were the same sex as the subject mice.

Results: The B6 mice did not show a preference for any partner strain while the BTBR mice preferred the B6 mice. Results from the bedding experiment were more complex with males and females having different profiles. Male B6 mice did not show a preference between the stranger mouse and bedding, while the male BTBR preferred the bedding regardless of stranger mouse strain.  Female B6 and BTBR mice preferred bedding when the stranger strain was different, no preference was observed with the stranger strain was the same.

Conclusions: BTBR mice have low sociability in general, prefer to spend time with the more social B6 mice when given a choice. This suggests that there is a perceptible difference between the strains that guides the choice of the BTBR mice into preferring the more social stranger mice. In the choice between bedding and a stranger mouse, behavior of the female mice was dependent on the stranger mouse strain (same or different from subject mouse strain). The male mice had a different pattern, the B6 mice investigated both the stranger mouse and stranger mouse bedding similarly regardless of the strain of the stranger mouse. Male BTBR mice spent more time with the bedding which may indicate some social anxiety associated with the awake moving stranger versus the similarly smelling bedding.