Typical development of synaptic and neuronal properties can proceed without microglia

Author:

O’Keeffe Mary,Booker Sam A,Walsh Darren,Li Mosi,Henley Chloe,de Oliveira Laura Simões,Liu Mingshan,Wang Xingran,Banqueri-Lopez Maria,Ridley Katherine,Dissanyake Kosala,Martinez-Gonzales Cristina,Craigie Kirsty,Vasoya Deepali,Leah Tom,He Xin,Hume David A,Duguid Ian,Nolan Matthew F,Qiu Jing,Wyllie David J. A.,Dando Owen R,Gonzales-Sulsar Alfredo,Gan Jian,Pridans Clare,Kind Peter C,Hardingham Giles EORCID

Abstract

AbstractBrain-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 (Csf1rΔFIRE/ΔFIRE) we find that neuronal physiology, synapse number and synaptic maturation are largely normal in CA1 of the hippocampus and somatosensory cortex during development. Seizure susceptibility and hippocampal-prefrontal cortex coherence in awake behaving animals, processes disrupted in mice deficient in microglia- enriched genes, are also normal. Similarly, segregation of eye-specific inputs into the lateral geniculate nucleus proceeds normally in the absence of microglia. Furthermore, transcriptomic analysis did not uncover substantial perturbation due to neurons and astrocytes due to microglial absence. Thus, in the absence of microglia, the brain retains the capacity to execute developmental synaptic refinement, maturation and connectivity.

Publisher

Cold Spring Harbor Laboratory

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