Cell proliferation and survival in the maternal dorsal raphe

DESCRIPTION (provided by applicant): The profound behavioral changes associated with pregnancy and the postpartum period include reduced anxiety and increased maternal caregiving. While most postpartum women experience decreased anxiety compared to pregnant and nonpregnant women, an estimated 10-20% of peripartum women report levels of anxiety reaching diagnostic criteria. Mood dysregulation during the peripartum period can derail bonding between mothers and offspring and impair offspring emotional and cognitive development. The proposed projects examine a novel neuroplastic feature that I discovered in the midbrain of peripartum rats, which may underlie emotional and behavioral changes associated with the peripartum period. Specifically, this research will focus on cell proliferation and survival in the maternal dorsal raphe (DR). The DR is the source of nearly all brain-derived serotonin, a neurotransmitter critically involved in both anxiety and maternal caregiving behaviors. The proposed projects include three Specific Aims designed to test the hypothesis that cells added to the DR during pregnancy and postpartum modulate the serotonergic system in ways critical for normal peripartum maternal and emotional behaviors. Aim 1 will determine when during the female reproductive cycle (early pregnancy, late pregnancy, lactation, and postweaning) DR cell proliferation and survival are increased above virgin levels. Aim 2 will define the neuronal or glil phenotype of newly added DR cells, as well as whether or not new neurons produce serotonin. Aim 3 will directly test the function of the newly added cells by preventing cell proliferation during pregnancy with an antimitotic agent and investigating several likely behavioral outcomes. Understanding the neural underpinnings of the dramatic behavioral and emotional changes occurring across the peripartum period will allow more efficient diagnosis and treatment of emotional disorders in mothers, thus improving their capacity for mothering and infant development.