Peripartum plasticity in the serotonergic dorsal raphe: Implications for postpartum socioemotional behavior and physiology

PERIPARTUM PLASTICITY IN THE SEROTONERGIC DORSAL RAPHE: IMPLICATIONS FOR POSTPARTUM SOCIOEMOTIONAL BEHAVIOR AND PHYSIOLOGY By Mary A. Holschbach Postpartum rats are highly maternal and show high aggression and low anxiety compared to nulliparous rats. To promote these dramatic changes in behavior, new mothers experience equally dramatic endocrine changes that elicit widespread neural plasticity. This neural plasticity includes cell birth and death in several regions of the peripartum forebrain, but such plasticity has never been reported in the dorsal raphe (DR), a midbrain site that provides most of the forebrain’s serotonin. Because 1) postpartum lesions of the dorsal raphe reduce offspring development and survival, 2) serotonin affects postpartum social behaviors including caregiving and aggression, and 3) serotonin modulates anxiety in nulliparous males and females, I hypothesized that motherhood alters DR plasticity and serotonin synthesis/metabolism to support postpartum changes in socioemotional behaviors. To test this hypothesis, I examined effects of reproductive state and maternal experience on DR cell proliferation, newborn cell survival, cell death, and many aspects of the serotonin synthesis/metabolism pathway, then tested postpartum social and emotional behavior after lesioning the serotonergic DR. I discovered that although an equal number of cells are born in the DR of virgin, pregnant, and postpartum rats, fewer cells survived into the late postpartum period compared to cells surviving into the early postpartum period. These late postpartum females also had the highest levels of cell death within the DR. Next, I determined that interacting with the litter reduced cell survival and increased cell death in the DR of late postpartum rats. These effects were not due to high maternal corticosterone because adrenalectomized and sham-operated postpartum rats had equivalent DR cell survival. DR newborn cell survival and cell death were related to changes in serotonin synthesis and metabolism because late postpartum rats also had lower levels of serotonin’s precursor (5-HTP) and metabolite (5-HIAA) than early postpartum rats. To begin to test the functional significance of these changes in neuroplasticity and neurochemical function, I performed serotonin-specific DR lesions using a saporin-conjugated toxin targeting the serotonin transporter. Lesioning the DR altered numerous postpartum behaviors. During undisturbed observations, lesioned animals actively nursed pups (in kyphosis) more and licked pups less. Lesioning the DR did not greatly affect anxiety-like behavior, but did reduce maternal aggression. These data demonstrate that the DR is a site of significant peripartum plasticity, and that, along with this plasticity, there are concurrent changes in local serotonin synthesis and metabolism. These neurochemical changes may guide postpartum behavioral adaptations because lesioning the DR of new mothers had numerous effects on postpartum social behaviors. Taken together, these data suggest that the DR is an integral part of the maternal neural network that guides the initiation, modulation, and regression of postpartum behaviors.