Microglia shape hippocampal networks but are dispensable for pruning of synapses during development

Abstract

Microglia, the brain-resident macrophages, are believed to sculpt developing neural circuits by eliminating excess synapses in a process called synaptic pruning, removing apoptotic neurons, and promoting neuronal survival. To elucidate the role of microglia during embryonic and postnatal brain development, we used a mouse model deficient in microglia throughout life as a consequence of deletion of the fms-intronic regulatory element (FIRE) in the Csf1r locus. Surprisingly, young adult Csf1r{Delta}FIRE/{Delta}FIRE mice displayed no changes in excitatory synapse number and spine density of CA1 hippocampal neurons compared to Csf1r+/+ littermates. However, CA1 neurons were less excitable, received less CA3 Schaffer collateral-mediated excitatory input and showed altered synaptic properties, but this did not affect novel object recognition. Cytokine profiling indicated an anti-inflammatory state along with increases in ApoE levels and astrocyte reactivity in brains of Csf1r{Delta}FIRE/{Delta}FIRE mice. Notably, these morphological and functional changes in Csf1r{Delta}FIRE/{Delta}FIRE mice closely resemble the effects of acute microglial depletion in adult mice that had undergone normal development. Thus, our findings challenge the prevailing view that microglia are indispensable for the establishment of neural networks during development.