The role of microglia in the second and third postnatal weeks of life in rat hippocampal development and memory

Microglia are resident immune cells of the central nervous system (CNS). In adulthood they are involved in surveillance and responses to pathogens and injury and prenatally they play a role in brain development. However, the role of microglia during the early postnatal period and how they impact development long-term remains poorly understood. Here, to investigate the specific role of microglia in postnatal development, we used a Cx3cr1-Dtr transgenic Wistar rat model to acutely ablate microglia from either postnatal day (P) 7 or 14. We specifically assessed how transient microglial ablation affected astrocytes and neurons acutely, during the juvenile period, and in adulthood. Hippocampal microglial numbers remained low at P21 in the P7-ablated animals and complexity remained reduced after P14-ablation. This protracted effect on these key immune cells led to a small but significant increase in CA1 mature neuron numbers and a significant increase in astrocyte density in the subgranular dentate gyrus in adults that had their microglia ablated at P14. However, these histological differences were small, and spatial and recognition memory in novel objection and place recognition tests were not affected. Overall, our data reveal for the first time that the transient depletion of microglia during the neonatal period impacts briefly on the brain but that the long-lasting effects are minimal. Neonatal microglia may be dispensable in the establishment of hippocampal brain function. These data also imply that novel therapeutic anti-inflammatories that cross the blood-brain barrier to inhibit microglia are unlikely to have long-term negative consequences if administered in the neonatal period.