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Schafer Lab works to unlock mystery of microglia function

UMMS researcher studying brain cells for greater understanding of central nervous system development

By Megan Bard and Bryan Goodchild

UMass Medical School Communications

November 02, 2015

Dorothy Schafer, PhD, is in search of a deeper understanding of microglial cells, which make up nearly 10 percent of brain cells and play a crucial role in providing the first line of immunity defense of the nervous system, but have been largely ignored by neurobiologists until recently.

“As neuroscientists, we still don’t understand how the brain is wired,” said Dr. Schafer, assistant professor of neurobiology, who established her lab at UMass Medical School in January. “I’m really interested in teasing out how these microglia regulate the development of the nervous system and brain wiring.”

Schafer’s work and expertise have been highlighted in articles that recently appeared in Scientific American, and Nature

Understanding the role of microglia could give scientists significant insight into devastating psychiatric disorders that have neurodevelopmental underpinnings, such as autism and schizophrenia, she said.

“We know that microglia are abnormal in these neurological disorders, but at this point we have no idea if there is a connection with abnormalities in brain wiring and behavior,” Schafer said.

Prior to establishing her lab at UMMS, Schafer studied neuroscience and behavior at Mount Holyoke College and earned a PhD from the University of Connecticut where she studied neuron-glia interactions in the Matthew Rasband lab. She continued her postdoc work at Boston Children’s Hospital in 2008 in Beth Steven’s lab where she became intrigued with microglia.

“I realized that microglia were relatively understudied in the field and were present at the right time and place to help shape the developing brain,” Schafer said. “I saw an opportunity to contribute to the field in a significant way and be on the ground floor of something that could potentially be very important in multiple contexts.”

Schafer’s work resulted in one of the first studies to demonstrate that microglia can actively participate in the remodeling of circuits in brain wiring over the course of healthy nervous system development.

“As the nervous system develops, you have way more synaptic connections between neurons than you need. We found that microglia were actually sculpting this immature connectivity by eating or engulfing less active synaptic connections,” Schafer said. She said the discovery was exciting and opened the field to the possibility that microglia may be performing a broad range of functions throughout the central nervous system.

Using mouse models in her lab at UMMS, Schafer and colleagues are focused on the role of microglia in synapse development and plasticity in the healthy and diseased nervous system.

“We are now imaging interactions between fluorescently labeled microglia and neural circuits while mice are awake and behaving and combining this with molecular genetic approaches to identify underlying mechanisms,” Schafer said.

By studying microglia-neural circuit interactions on a cellular and molecular level, Schafer hopes to gain a greater understanding of the basic science underlying the development of neural circuits and apply these mechanisms to understand how abnormalities in microglia function could underlie complicated neurological disorders.