Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction

TLDR

Microglia are motile glial cells implicated in synaptic pruning, but direct phagocytosis of synapses has not been reported, leaving questions about which synaptic structures are targeted and how the process occurs. The study aims to propose a mechanism for microglia’s facilitatory role in synaptic circuit remodeling and maturation. Using light‑sheet fluorescence microscopy and correlative light‑electron microscopy in developing organotypic hippocampal cultures, the authors tracked microglia–synapse interactions. They observed selective partial phagocytosis (trogocytosis) of presynaptic elements and microglia‑induced postsynaptic spine‑head filopodia.

Abstract

Abstract Microglia are highly motile glial cells that are proposed to mediate synaptic pruning during neuronal circuit formation. Disruption of signaling between microglia and neurons leads to an excess of immature synaptic connections, thought to be the result of impaired phagocytosis of synapses by microglia. However, until now the direct phagocytosis of synapses by microglia has not been reported and fundamental questions remain about the precise synaptic structures and phagocytic mechanisms involved. Here we used light sheet fluorescence microscopy to follow microglia–synapse interactions in developing organotypic hippocampal cultures, complemented by a 3D ultrastructural characterization using correlative light and electron microscopy (CLEM). Our findings define a set of dynamic microglia–synapse interactions, including the selective partial phagocytosis, or trogocytosis ( trogo -: nibble), of presynaptic structures and the induction of postsynaptic spine head filopodia by microglia. These findings allow us to propose a mechanism for the facilitatory role of microglia in synaptic circuit remodeling and maturation.