Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction

Laetitia Weinhard, Giulia Bartolomei, Giulia Bolasco, Pedro Machado, Nicole L. Schieber, Urte Neniskyte, Melanie Exiga, Auguste Vadisiute, Angelo Raggioli, Andreas Schertel, Yannick Schwab and Cornelius T. Gross ()
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Laetitia Weinhard: European Molecular Biology Laboratory (EMBL)
Giulia Bartolomei: European Molecular Biology Laboratory (EMBL)
Giulia Bolasco: European Molecular Biology Laboratory (EMBL)
Pedro Machado: European Molecular Biology Laboratory (EMBL)
Nicole L. Schieber: European Molecular Biology Laboratory (EMBL)
Urte Neniskyte: European Molecular Biology Laboratory (EMBL)
Melanie Exiga: European Molecular Biology Laboratory (EMBL)
Auguste Vadisiute: European Molecular Biology Laboratory (EMBL)
Angelo Raggioli: European Molecular Biology Laboratory (EMBL)
Andreas Schertel: ZEISS Group
Yannick Schwab: European Molecular Biology Laboratory (EMBL)
Cornelius T. Gross: European Molecular Biology Laboratory (EMBL)

Nature Communications, 2018, vol. 9, issue 1, 1-14

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.

Date: 2018
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DOI: 10.1038/s41467-018-03566-5

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