PRENATAL CORTICOSTERONE TREATMENT IMPACTS HIPPOCAMPAL DEVELOPMENT AND ADULT BEHAVIOR: A FOCUS ON AREA CA2

Prenatal stress is a risk factor for several neurodevelopmental and neuropsychiatric disorders. During heightened periods of stress, Glucocorticoids such as cortisol and corticosterone (CORT) are produced. These stress-signaling hormones bind to their receptors, the glucocorticoid and mineralocorticoid receptors, where they act as transcription factors to regulate gene expression in their target tissues, including the brain. Within the brain is the hippocampus, which is enriched with MRs beginning early in prenatal development, making it a viable target for circulating stress hormones associated with prenatal stress. Area CA2 is present in the hippocampus of many mammalian species and has the highest expression of MRs in thebrain. Interestingly, conditional genetic deletion of MRs in mice eliminates expression of CA2-specific molecular markers, alters CA2’s synaptic plasticity profile, and impairs social behavior, indicating a critical role of MR function in CA2’s identity. Yet to be determined is how prenatal treatment with the stress hormone and MR agonist, CORT, affects the expression of CA2’s molecular profile, its connectivity to other brain regions, and related behaviors. To investigate this, I treated pregnant dams with CORT or a vehicle in their home-cage drinking water and examined the resulting offspring at different developmental stages. Our findings suggest that stress experienced in the prenatal environment alters the connectivity of area CA2 to other areas of the brain. In addition, prenatal CORT disrupts the brain’s hormonal profile and impacts novelty-reactivity and anxiety-like behaviors in sex-specific ways during adulthood.