Motherhood and Infant Contact Regulate Neuroplasticity in the Serotonergic Midbrain Dorsal Raphe

The adult brain shows remarkable neuroplasticity in response to hormones and the socioemotional modifications that they influence. In females with reproductive and maternal experience, this neuroplasticity includes the birth and death of cells in several forebrain regions involved in maternal caregiving and postpartum affective state. Such plasticity in midbrain sites critical for these behavioral and emotional processes has never been examined, though. By visualizing bromodeoxyuridine (BrdU) to label mitotic cells, NeuroD for neuronal precursors, and TUNEL to identify dying cells, we found that the midbrain dorsal raphe nucleus (DR, the source of most ascending serotoninergic projections) exhibited significant neuroplasticity in response to motherhood. Specifically, BrdU analyses revealed that DR newborn cell survival (but not proliferation) was regulated by reproductive state, such that cells born early postpartum were less likely to survive 12 days to reach the late postpartum period compared to cells born during late pregnancy that survived 12 days to reach the early postpartum period. Many of the surviving cells in the DR were NeuN immunoreactive, suggesting a neuronal phenotype. Consistent with these findings, late postpartum rats had fewer NeuroD-immunoreactive DR cells than early postpartum rats. Maternal experience contributed to the late postpartum reduction in DR newborn cell survival because removing the litter at parturition increased cell survival as well as reduced cell death. Unlike cytogenesis in the maternal hippocampus, which is reduced by circulating glucocorticoids, DR newborn cell survival was unaffected by postpartum adrenalectomy. These effects of reproductive state and motherhood on DR plasticity were associated with concurrent changes in DR levels of serotonin's precursor, 5-HTP, and its metabolite, 5-HIAA. Our results demonstrate for the first time that cytogenesis occurs in the midbrain DR of any adult mammal, that DR plasticity is influenced by female reproductive state and maternal experience, and that this plasticity is accompanied by changes in DR serotonergic function. Because serotonin is critical for postpartum caregiving behaviors and maternal affective state, plasticity in the DR may contribute to the neurochemical changes necessary for successful motherhood.