9458101 Berger-Sweeney The proposed studies will examine mechanisms that underlie sexual dimorphism of cerebral cortical structure and cognitive functions in mice. More specifically, the studies will focus on how cortically-projecting neurons in the basal forebrain (BF) influence the developing cortex and cognition in the two sexes. A BF lesion model will grow to adulthood. Previous studies show that a neonatal BF lesion leads to persistent alterations in cortical morphology and to cognitive deficits in adulthood. Recent studies show that lesion-induced structural and functional deficits are more pronounced in male than in female mice. For the proposed studies, a combination of neurochemical, anatomical and behavioral methods will be used to examine mechanisms that underlie these sex differences. Critical questions to be addressed include: Does the BF influence cortical maturation at different times in males and females? What neurotransmitters are responsible for morphological and behavioral differences between the sexes? Do gonadal hormones differentially interact with the developing BF system in the two sexes? Answers to these questions will provide exciting insights into how sex differences in cortical maturation may relate to sex-specific cognitive development.
