They help protect the brain from harmful invaders, clear away damaged neurons, and support normal brain development. Researchers at Columbia's Zuckerman Institute have now found for the first time that human microglia, much like human neurons, mature far more slowly than comparable cells in other animals. "This slow development may help human microglia influence the human brain in ways that enable our powerful cognitive abilities," said Carlos Diaz-Salazar, PhD, the lead author of a new Neuron study on the subject, who carried out the work while in the lab of Franck Polleux, PhD.
A Human-Specific Gene With an Unusual Role The Polleux lab has spent more than 15 years studying SRGAP2, one of several dozen genes that were duplicated specifically in humans. The group's broader goal is to understand the biological features that distinguish the human brain from those of other animals. Polleux showed that human-specific copies of SRGAP2 increase the number of synapses, or connections, made by neurons while also causing those synapses to mature very slowly.
Both traits are distinctive features of human neurons among mammals. The result is a denser and stronger network of neuronal connections that may enhance the brain's ability to process and store information. Diaz-Salazar found something unexpected.
Human-specific copies of SRGAP2 were nearly 10 times more abundant in microglia than in neurons. "So the question was, 'Why on Earth is this gene so active in microglia?'" recalled Dr. Polleux, a principal investigator at the Zuckerman Institute.
Microglia Help Shape Developing Brain Circuits Over roughly the past two decades, scientists have learned that microglia do much more than fight infections and help repair brain damage. These cells, which account for 5 to 10 percent of brain cells, also help organize the developing brain. During development, microglia influence which synapses neurons retain and which ones are eliminated.
They can also make synapses more or less responsive, helping fine-tune communication within brain circuits. Experiments using mice and human cells showed that the human-specific copies of SRGAP2 dramatically slow the development of human microglia. Human microglia take about four to eight years to mature, while microglia in mice reach maturity in roughly three weeks.
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