The development of social behaviors in C57BL/6J and BALB/cJ mice

Autism spectrum disorders (ASD) are marked by impairments in social interactions, including reduced sociability (reduced tendency to seek social interactions) beginning in early childhood, but the neurobiology of sociability is poorly understood. Mouse models provide a powerful tool by which to investigate the underlying neurobiology and genetics of sociability. Sociability can be measured quantitatively in mice using the Social Choice Test, in which a test mouse is allowed to investigate an unfamiliar stimulus mouse, whose movement about the testing arena is highly restricted. We tested hypotheses about the most reliable and valid measures of sociability in the social choice test, the development of sociability and brain, and the effects of serotonin on sociability. Our data indicate that the amount of investigation of the stimulus mouse by the test mouse is the most reliable and ecologically valid sociability measurement in the Social Choice Test. During prepubescence mice of the BALB/cJ inbred strain are less sociable than mice of C57BL/6J inbred strain. This strain difference diminishes or disappears by adulthood. A similar pattern manifests for passive, but not active, social behaviors with littermates in home cage environments, in which social behaviors are more naturalistic than in the Social Choice Test. The two genetically-divergent strains also show differential effects of environmental and developmental factors on sociability. C57BL/6J mice born into litters with a smaller perinatal litter size or a greater perinatal ratio of females to males tend to be more sociable across prepubescence, pubescence, and adulthood. These litter characteristics evidently do not affect BALB/cJ sociability, but unlike C57BL/6J mice, BALB/cJ mice with smaller brains tend to be less sociable, at least at 30 days of age. Both sets of these results are of interest because perinatal testosterone and altered brain size may influence the social impairments found in ASD patients. Additionally, ASD patients often display abnormalities of the serotonergic system, and acute pharmacological manipulation of the serotonergic system in prepubescent C57BL/6J and BALB/cJ mice influences their sociability. Further study of litter characteristics, brain size, and serotonin will further illuminate the biological mechanisms that influence the typical development and the impairment of social behaviors.