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Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction

Laetitia Weinhard1, Giulia di Bartolomei1, Giulia Bolasco1

  • 1Epigenetics and Neurobiology Unit, European Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00015, Monterotondo, Italy.

Nature Communications
|March 28, 2018
PubMed

Insights

Microglia (immune cells in the brain) nibble (trogocytosis) presynaptic structures and induce postsynaptic filopodia, facilitating synaptic maturation. This reveals dynamic microglia-synapse interactions crucial for neuronal circuit development.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Immunology

Background:

  • Microglia, the brain's resident immune cells, are implicated in synaptic pruning during neural development.
  • Impaired microglial phagocytosis of synapses is linked to abnormal synaptic connections.
  • Direct visualization and mechanistic understanding of microglia-synapse interactions have been lacking.

Purpose of the Study:

  • To directly observe and characterize the dynamic interactions between microglia and synapses during development.
  • To elucidate the specific synaptic structures involved in microglial phagocytosis.
  • To understand the mechanisms by which microglia influence synaptic maturation.

Main Methods:

  • Light sheet fluorescence microscopy was employed to track microglia-synapse interactions in real-time.
  • Correlative light and electron microscopy (CLEM) provided high-resolution 3D ultrastructural details.
  • Developing organotypic hippocampal cultures were used as the experimental model.

Main Results:

  • Defined dynamic interactions between microglia and synapses.
  • Observed selective partial phagocytosis (trogocytosis) of presynaptic structures by microglia.
  • Identified microglial induction of postsynaptic spine head filopodia.

Conclusions:

  • Microglia engage in trogocytosis of presynaptic components.
  • Microglia actively shape postsynaptic structures.
  • These interactions provide a mechanism for microglial facilitation of synaptic circuit remodeling and maturation.

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