Microglia · Grey Matter

Microglia are the brain's resident immune cells, which patrol the tissue, clear debris and dying cells, and remove synapses that are tagged for elimination, so they keep the wiring tidy as well as defending it.

Microglia. Microglia are the brain's resident immune cells, which patrol the tissue, clear debris and dying cells, and remove synapses that are tagged for elimination, so they keep the wiring tidy as well as defending it.

They make up roughly a tenth of the cells of the brain (estimates range from about 5 to 12 % depending on region). Unlike the other glia they come from the immune system: their ancestors enter the brain from the embryonic yolk sac early in development and then renew themselves locally. In healthy tissue each microglial cell holds a territory and keeps extending and retracting its fine branches, sampling its surroundings every few minutes. When it detects injury or infection it changes shape, moves to the site, engulfs what it finds and releases signalling molecules (cytokines) that recruit other cells.

They prune synapses. During development, weak or unused synapses are tagged with complement proteins such as C3, and microglia carrying the matching receptor (CR3) engulf them; mice lacking these molecules keep too many synapses.

Their response can harm. Prolonged activation, with its inflammatory signals, is part of the picture in many neurodegenerative diseases and after injury, and inflammatory signals also raise neuronal excitability.

They talk with astrocytes and neurons. Neurons signal through molecules that hold microglia back (CD200, fractalkine), and the balance between these signals decides how aggressive microglia become.

Microglia are the gardeners of the synapse as well as its guards.

The same engulfing machinery that clears infection is used to cut connections the circuit no longer uses.

Questions: How do microglia decide which synapses to remove? During development, weak or little-used synapses become coated with complement proteins (C1q, then C3), the same tags the immune system uses to mark bacteria for destruction. Microglia carry the matching receptor, CR3, and engulf the tagged terminals; in the developing visual thalamus of mice, fragments of retinal terminals end up inside microglial lysosomes, and inputs that are less active are removed preferentially. Mice lacking C3 or CR3 keep too many synapses. Signals on healthy synapses that hold microglia back, such as CD47, protect the connections the circuit uses.