ISDN2014_0326: Developmental trajectories of deep gray matter structures in healthy children and adults

own fmr1 genotype, suggesting that maternal factors other than fmr1 transmission have substantial effects on offspring behavior. Here we asked whether the maternal genotype affects offspring social behavior, a phenotype of particular interest given its pervasiveness in numerous psychiatric conditions including autism spectrum disorder. We found that reduced maternal fmr1 expression was sufficient to induce altered social behaviors in both fmr1-/y (knockout; KO) and fmr1+/y (wildtype; WT) offspring, with WT animals exhibiting an intermediate level of enhanced approach and reduced avoidance behaviors. We observed no differences in olfactory discrimination, indicating that abnormal odorant cue processing is an unlikely cause of the observed social phenotype. To narrow down the developmental period sensitive to the maternal genotype effect, we crossfostered pups between WT and H females and found that exposure to either prenatal or postnatal H maternal environment is sufficient to induce the abnormal social phenotype. Furthermore, crossfostering to a postnatal WT environment fails to rescue the behavioral effect of a prenatal H maternal environment. Taken together, our data shows that the abnormal social phenotype, like hyperactivity, is dependent in part on the maternal fmr1 genotype and that this intergenerational effect is not mediated by genetic transmission. Although it is well established that prenatal and/or postnatal maternal factors including malnutrition, infections and stress can alter behaviors associated with autism and schizophrenia, additional studies are needed to identify the specific fmr1-associated maternal factor/s responsible for inducing the effects reported here.