Impact Of Gestational Immune Activation On The Female Brain

Under the influence of surging hormones, the female brain undergoes substantial rearrangements on the brain during pregnancy to ensure behavioral adaptations of the mother after birth, which promote infant care. At the same time, these extensive reorganizations render the female brain malleable and especially susceptible to external influences. Maternal immune activation (MIA) is one of the most common complications during pregnancy, predominantly evoked by viral infection. We have recently shown in the mouse model that MIA disrupts mother-to-offspring bonding and maternal care behavior postpartum, together with alterations in the hypothalamus of the brain. However, the temporal trajectory of changes in the female brain in response to the immune challenge and its impact on the physiological neural adaptations during pregnancy remain unknown. Here we will probe the time course of structural and functional gestational rearrangements in the female brain and characterize the deviations induced by MIA in a longitudinal, preclinical study design. We seek to capture the dynamic changes in female brain anatomy and physiology, spanning a period from prior to conception until post-partum and to relate the neural consequences of MIA to dysfunctional maternal care behavior. To this end we will stimulate pregnant female mice with a substance mimicking viral infection (Poly I:C). In-vivo functional and structural magnetic resonance imaging (MRI) scans will be performed before mating, during pregnancy and on postnatal day in control and MIA mothers. Maternal behavior will be assessed in the pup retrieval assay on day 6 after birth. Animals will then be sacrificed and perfused for high-resolution post-mortem anatomical scans This project is first to assess how gestational infection derails the dynamic changes in neural connectivity and anatomy during pregnancy and in the perinatal period to give rise to a significant disruption of maternal care behavior post-partum.