Arg1+ microglia are critical for shaping cognition in female mice

Diversity within microglia, the resident brain immune cells, is reported. Whether microglial subsets constitute different subtypes with intrinsic properties and unique functions has not been fully elucidated. Here, we describe a microglial subtype characterized by the expression of the enzyme Arginase-1, i.e. Arg1+microglia, which is found predominantly in the cholinergic neuron-rich forebrain region during early postnatal development. Arg1+ microglia are frequently observed in close apposition to neurons and exhibit a distinct molecular signature including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3 and Mgl2. Arg1-knockout in microglia results in a deficient cholinergic innervation along with impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, impaired long-term potentiation and cognitive behavioural deficiencies in female mice. Our results expand on microglia diversity and provide insights into distinctive spatiotemporal functions exerted by microglial subtypes.