Typical development of synaptic and neuronal properties can proceed without microglia in the cortex and thalamus
Mary O’KeeffeiD, Sam A. BookeriD, Darren A. WalshiD, Mosi LiiD, Chloe Henley, Laura Simões de OliveiraiD, Mingshan LiuiD, Xingran WangiD, María BanqueriiD, Katherine RidleyiD, Kosala N. DissanayakeiD, Cristina Martinez‐GonzaleziD, Kirsty J. CraigieiD, Deepali VasoyaiD, Tom Leah, Xin HeiD, David Arthur HumeiD, Ian DuguidiD, Matthew F. NolaniD, Jing QiuiD, David J. A. WyllieiD, Owen DandoiD, Alfredo Gonzalez‐SulseriD, Jian GaniD, Clare PridansiD, , Giles E. HardinghamiD
Abstract
Brain-resident macrophages, microglia, have been proposed to play an active role in synaptic refinement and maturation, influencing plasticity and circuit-level connectivity. Here we show that a variety of neurodevelopmental processes previously attributed to microglia can proceed without them. Using a genetically modified mouse which lacks microglia (Csf1r{Delta}FIRE/{Delta}FIRE) we find that intrinsic properties, synapse number and synaptic maturation are largely normal in the hippocampal CA1 region and somatosensory cortex at stages where microglia have been implicated. Seizure susceptibility and hippocampal-prefrontal cortex coherence in awake behaving animals, processes disrupted in mice deficient in microglia-enriched genes, are also normal. Similarly, eye-specific segregation of inputs into the lateral geniculate nucleus proceeds normally in the absence of microglia. Single cell/nucleus transcriptomic analyses of neurons and astrocytes did not uncover any substantial perturbation due to microglial absence. Thus, the brain possesses remarkable adaptability to execute developmental synaptic refinement, maturation and connectivity in the absence of microglia.
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