Microglia Pruning Brain Synapses Captured on Film For The First Time

Source: European Molecular Biology Laboratory

Summary: For the first time, researchers in a study found that the special glial cells help synapses grow and rearrange and demonstrated the essential role of microglia in brain development.

Microglia are glial cells that are around one in 10 brain cells. Cousins of macrophages, they act as the first and main contact in the central nervous system’s active immune defense. They also guide healthy brain development. For the first time, researchers from the European Molecular Biology Laboratory (EMBL) have captured microglia pruning synaptic connections between brain cells. Their findings show that the special glial cells help synapses grow and rearrange and demonstrated the essential role of microglia in brain development. They have proposed that microglia prune synapses as an essential step during early circuit refinement. The study findings were published in the journal Nature Communications.

Glial cells

Multiple synapse heads send out filopodia (green) converging on one microglia (red), as seen by focused ion beam scanning electron microscopy (FIBSEM). Credit: L. Weinhard, EMBL Rome

The research team at EMBL set out on a massive imaging study to observe this process in action in the mouse brain. Around half of the time, microglia contact a synapse, and the synapse head sends out thin projections called filopodia to contact them. It turns out that microglia might underly the formation of double synapses, in which the terminal end of a neuron releases neurotransmitters onto two neighboring partners instead of one. This process can support effective connectivity between neurons. By combining correlative light and electron microscopy (CLEM) and light sheet fluorescence microscopy the team was able to make the first movie of microglia eating synapses.

Senior scientist, Cornelius Gross said, “This is what neuroscientists have fantasized about for years, but nobody had ever seen before”, “These findings allow us to propose a mechanism for the role of microglia in the remodeling and evolution of brain circuits during development.”

More information: Laetitia Weinhard et al, “Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction”, Nature Communications (2018). doi:10.1038/s41467-018-03566-5

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