# ARG1-expressing microglia show a distinct molecular signature and modulate postnatal development and function of the mouse brain

## TL;DR

A specific type of brain immune cell, ARG1-expressing microglia, plays a unique role in brain development and cognitive function in mice.

## Contribution

Identifies a novel microglial subtype with distinct molecular and functional roles in postnatal brain development.

## Key findings

- ARG1+ microglia are enriched in phagocytic inclusions and show a unique gene expression profile.
- ARG1 knockdown impairs hippocampal cholinergic innervation and spine maturation in mice.
- ARG1+ microglia influence cognitive behavior in a sex-dependent manner.

## Abstract

Molecular diversity of microglia, the resident immune cells in the CNS, is reported. Whether microglial subsets characterized by the expression of specific proteins constitute subtypes with distinct functions has not been fully elucidated. Here we describe a microglial subtype expressing the enzyme arginase-1 (ARG1; that is, ARG1+ microglia) that is found predominantly in the basal forebrain and ventral striatum during early postnatal mouse development. ARG1+ microglia are enriched in phagocytic inclusions and exhibit a distinct molecular signature, including upregulation of genes such as Apoe, Clec7a, Igf1, Lgals3 and Mgl2, compared to ARG1– microglia. Microglial-specific knockdown of Arg1 results in deficient cholinergic innervation and impaired dendritic spine maturation in the hippocampus where cholinergic neurons project, which in turn results in impaired long-term potentiation and cognitive behavioral deficiencies in female mice. Our results expand on microglia diversity and provide insights into microglia subtype-specific functions.

The molecular diversity of microglia has been described. Here the authors show that ARG1-expressing microglia are enriched in phagocytic inclusions and are involved in hippocampal innervation and spine maturation in mice. ARG1-expressing microglia also modulate cognition in a sex-dependent manner.