Microglia: The Constant Gardeners

The work required the mind of an engineer and the hands of a surgeon. Axel Nimmerjahn had both.It was 2002 when Nimmerjahn, then a graduate student at the Max Planck Institute for Medical Research in Heidelberg, Germany, began trying to spy on the everyday activity of the mysterious brain cells known as microglia. Others had caught glimpses of the cells in their spider-like resting state, but only in slices of dead tissue. No one had been able to see them in a live brain. That's because microglia — which, unlike other cells in the brain, are part of the immune system — are extremely sensitive. Cut a nerve, or release infectious bacteria into brain tissue, and microglia spring into action, retracting their many appendages and morphing into big, round blobs that gobble up pathogens and clear away cellular wreckage.To see the cells without disturbing them, Nimmerjahn used a newly published approach for imaging a live mouse brain. After anaesthetizing the animal and peeling back its scalp, he removed the top two-thirds of the skull's thickness and shaved the bone down to just 20 micrometres — thin enough for light to penetrate, but thick enough to avoid setting off the microglia. The work progressed slowly — Nimmerjahn had to douse the surgical site with cooling fluid after realizing that even the heat from scraping could aggravate the cells. But within a few months at the bench, he was able to record some time-lapse movies.He was floored by what he saw: 'resting' microglia are anything but. Their delicate branches snake through densely packed brain tissue, constantly extending and shrinking and re-growing. “They're very dynamic, much more than any other cell in the adult brain,” says Nimmerjahn, now a biophysicist at the Salk Institute in La Jolla, California. He calculated that the cells' concerted movements could survey the entire brain every couple of hours. But it was unclear why the microglia were moving so much, Nimmerjahn says. “Why does the brain invest so much energy?”Read more at...Nature, May 2012.