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Nat Commun. 2018 Mar 26;9(1):1228. doi: 10.1038/s41467-018-03566-5.

Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction.

Author information

1
Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00015, Monterotondo, Italy.
2
Electron Microscopy Core Facility, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117, Heidelberg, Germany.
3
Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117, Heidelberg, Germany.
4
Department of Neurobiology and Biophysics, Life Science Center, Vilnius University, Sauletekio al. 7, Vilnius, 10257, Lithuania.
5
Carl Zeiss Microscopy GmbH, ZEISS Group, Carl-Zeiss-Strasse 22, 73447, Oberkochen, Germany.
6
Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00015, Monterotondo, Italy. gross@embl.it.

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.

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PMID:
29581545
PMCID:
PMC5964317
DOI:
10.1038/s41467-018-03566-5
[Indexed for MEDLINE]
Free PMC Article

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