Green for go and eat synapses (Image: Gerry Shaw/Wikimedia)

USE it or lose it: a class of immune cell demolishes idle circuits and connections in the brain, even a healthy one. Understanding more about the process could help prevent the onset of degenerative brain diseases.

Until now, microglia have been dismissed as simple immune cells that do little more than protect brain cells from damage and tidy up in the aftermath of disease.

“The idea they can clean up brain debris has been well established in studies of brain disease,” says Beth Stevens of Boston Children’s Hospital. “But now, even without damage, we’ve found them to respond to subtle changes in synaptic function.”


Stevens and her colleagues manipulated mice to make one eye more active than the other, creating a disparity in activity between the two neural circuits linking the eyes to the brain.

With the help of dyes to distinguish the signals from the left and right eyes, they saw in post-mortems that microglia had preferentially pruned the connections, or synapses, from circuits serving the underactive eye. Synapses were marked out for destruction through labelling with an immune chemical called C3 (Neuron, DOI: 10.1016/j.neuron.2012.03/026).

“We think C3 is an ‘eat me’ signal,” says Stevens.

Finding out why some synapses but not others are earmarked for elimination could point to ways of preventing degenerative brain diseases.

“Early synapse loss is a feature of many neurodegenerative diseases,” says Stevens. “So there’s lots of excitement about finding out what the trigger is.”

“Microglia were considered to be just garbage collectors,” says Francesca Peri of the European Molecular Biology Laboratory in Heidelberg, Germany. “They are turning out to be far more interesting – but before we can understand their role in disease, we need to understand what these cells do normally.”