How microglia are prompted to change their state to adapt to different areas of the brain

From everyday actions like walking and talking to feats of athletic or academic excellence, the brain is constantly acquiring and seamlessly processing information to produce these incredible behaviors. The process requires a whole orchestra of cells listening to each other and tuning their functions to harmonize together. One of the remaining, most fundamental questions in neuroscience asks how cells in the brain move, interact, and coordinate with each other to produce these activities.

In the brain, this cellular symphony includes not only neurons, but cells that normally play a role in defending the body against pathogens. One group are tiny immune cells called microglia, which researchers are increasingly learning play oversized roles in brain function, health, and disease. The cells are also gaining increased attention for their roles in assembling and maintaining neural circuits, and how they are able to change their molecular identity to match their environment. To neuroscientists, the mystery has long been how they make this change.

In a new report in Nature, a team of researchers from the lab of Golub Family Professor of Stem Cell and Regenerative Biology Paola Arlotta and from the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard come closer to answering this question. The paper, published Wednesday, shows that microglia cells “listen in” to neighboring neurons and change their molecular state to match them.

“When they were first discovered, microglia were assumed to be simply scavengers, cleaning up cell debris and helping to fight off pathogens,” said Jeffery Stogsdill, who led the study as a postdoctoral researcher in the Arlotta Lab. “Now we know that microglia can interact with neurons in very sophisticated ways that can affect neuron function.”

This discovery could one day open the door for lines of research that can target the communications between microglia and their neuron partners with pinpoint accuracy (disorders like autism and schizophrenia arise when these communications between cells go awry).

“You would no longer have to treat, for instance, microglia as one blanket cell type when trying to affect the brain,” Stogsdill continues. “We can target very specific states, or we can target very specific subtypes of neurons with the ability to change specific states of microglia. It allows us to have high-level granularity.”

The study provides unique insight into how different cell types work together in harmony.

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