Microglia filmed shaping synapses for the first time.

Acting as natural computers, our brains contain trillions of cells to store memory and control the body’s functions and emotions.  Around one in ten of the countless cells in the human brain are microglia, regulating the first and main contact in the central nervous system’s active immune defense as well as guiding healthy brain development. Researchers have proposed microglia pluck off and eat synapses, connections between brain cells, as an essential step in the pruning of connections during early circuit refinement.  However, until now, no one has seen them do it.  Now, a study from researchers at EMBL captures microglia ‘nibbling’ on brain synapses. The team states their findings show specialized glial cells help synapses grow and rearrange, demonstrating the essential role of microglia in brain development.  The opensource study is published in the journal Nature Communications.

Previous studies have shown microglia are highly motile glial cells hypothesized to mediate synaptic pruning during neuronal circuit formation. Disruption of signaling between microglia and neurons is known to lead 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 with fundamental questions remaining regarding the precise synaptic structures and phagocytic mechanisms involved.  The current study shows microglia directly engulf and eliminate synaptic material via trogocytosis, or ‘nibbling’, at synaptic structures.

The current study combines electron microscopy and light-sheet fluorescence microscopy to make the first movie of microglia eating synapses.  Results show around half of the time microglia contact a synapse, the synapse head sends out thin projections, known as filopodia, to greet them. In one case the group witnessed fifteen synapse heads extended filopodia toward one single microglia as it picked on a synapse, meaning that microglia actually induce their growth most of the time.

The lab states microglia might underly the formation of double synapses, where the terminal end of a neuron releases neurotransmitters onto two neighboring partners instead of one. They go on to add this process can support effective connectivity between neurons and shows microglia are broadly involved in structural plasticity, possibly inducing the rearrangement of synapses, a mechanism underlying learning and memory.

The team surmises their findings allow them to propose a mechanism for the role of microglia in the remodeling and evolution of brain circuits during development.  For the future, the researchers plan to investigate the role of microglia in brain development during adolescence and the possible link to the onset of schizophrenia and depression.

Source: European Molecular Biology Laboratory (EMBL)

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