Lifelong absence of microglia alters hippocampal glutamatergic networks but not synapse and spine density

Microglia sculpt developing neural circuits by eliminating excess synapses in a process called synaptic pruning, by removing apoptotic neurons, and by 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 by deletion of the fms-intronic regulatory element (FIRE) in the Csf1r locus. Surprisingly, young adult Csf1r Delta FIRE/Delta FIRE mice display no changes in excitatory and inhibitory synapse number and spine density of CA1 hippocampal neurons compared with Csf1r + /+ littermates. However, CA1 neurons are less excitable, receive less CA3 excitatory input and show altered synaptic properties, but this does not affect novel object recognition. Cytokine profiling indicates an anti-inflammatory state along with increases in ApoE levels and reactive astrocytes containing synaptic markers in Csf1r Delta FIRE/Delta FIRE mice. Notably, these changes in Csf1r Delta FIRE/Delta FIRE mice closely resemble the effects of acute microglial depletion in adult mice after normal development. Our findings suggest that microglia are not mandatory for synaptic pruning, and that in their absence pruning can be achieved by other mechanisms. Microglia-deficient mouse brains develop with normal hippocampal synapse numbers and pyramidal cell spine density, but deficits in the full maturation of glutamatergic networks, suggesting that microglia are dispensable for synaptic pruning but not for fine-tuning excitatory transmission.Excitatory and inhibitory synapse number and spine density of CA1 pyramidal cells in adult Csf1r Delta FIRE/Delta FIRE mice lacking microglia at all developmental stages are unaltered. Microglial absence causes deficits in CA3 - CA1 excitatory neurotransmission and pre- and postsynaptic function, without alterations in hippocampal-related behavior. Anti-inflammatory cytokines are increased and reactive astrocytes characterized by higher levels of GFAP and MEGF10 in the hippocampus of Csf1r Delta FIRE/Delta FIRE mice. Microglia-deficient mouse brains develop with normal hippocampal synapse numbers and pyramidal cell spine density, but deficits in the full maturation of glutamatergic networks, suggesting that microglia are dispensable for synaptic pruning but not for fine-tuning excitatory transmission.