Neuroscience’s Michelle Olsen using NIH grant to study one of the final frontiers: the brain

19 Mar 2021

Michelle Olsen, wearing a COVID mask, red blouse, and gray blazer, poses for a photograph inside the Life Sciences 1 building on campus.

Of all the worlds still to be explored, among the most mysterious may be closest to home. Indeed, it may be right between your ears.

A type of cell called the astrocyte accounts for more than 25 percent of the human brain, yet a small percentage of how this cell function contributes to brain function is actually understood.

Virginia Tech neuroscientist Michelle Olsen seeks to change that through a new five-year, $1.6 million grant from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health. She hopes her work will one day allow scientists to more deeply understand how this cell develops and functions in the healthy brain so that they can better treat neurodevelopmental disorders and neurological disease.

“There is so much about the brain that is still to learn,” said Olsen, an associate professor in the School of Neuroscience, part of the Virginia Tech College of Science, and director of the director of the recently approved neuroscience Ph.D. program. “We’re really at the bottom of an exponential learning curve.”

Astrocytes appear, or are born, late in the third trimester of fetal development, well after their more well-studied neighbors, the neurons. Astrocytes produce long tentacles or cell processes that appear to wrap around many points of contact, or synapses, between neurons, protecting and stabilizing these vital connections. But so far scientists know little about what “recruits” these astrocytic processes to neuronal synapses.

Yet, Olsen and her lab may have identified an important molecular player in that process. Scientists have long known that neurons release at the synapse a protein, “brain-derived neurotrophic factor” or BDNF, to aid in neuron-to-neuron communication, growth and function. Astrocytes produce the protein TrkB — that’s short for Tropomyosin receptor kinase B — a receptor for BDNF. Olsen suspects this BDNF/TrkB pathway facilitates neuron-to-astrocyte communication — a disruption of which could alter the development of astrocytes and, ultimately, the brain itself.

“We may have been missing a good part of the story by focusing on this pathway only in neurons,” she said. “It may turn out that this signaling pathway, which is critical for early brain development, is just as important in astrocytes. You can imagine if the cells do not develop properly then they don’t ever really normalize.”

The research is much too new to even hypothesize about potential medical benefits, Olsen added: “This is very basic science, really just trying to understand how the brain works normally. How does the astrocyte know where it needs to go?”

Beatriz Torres, a neuroscience doctoral student who works in Olsen’s lab, added, “I am very excited about the grant and the projects that it has outlined. Not very much is known about what actually draws an astrocyte process to a synapse in the first place. Understanding what these cues are could offer us novel therapeutic targets for neurodevelopmental and neuropsychiatric disorders.”

Scientific and technological advancements have been a major driver behind Olsen’s discoveries. The current study will be conducted in the mouse, a mammalian model system often used in neuroscience research. Olsen, and researchers like her, take advantage of the ability to manipulate the genome of this animal, allowing for specific manipulation of the BDNF/TrkB pathway only in the astrocytes.

The NIH grant allows Olsen’s team to use a new serial block-face scanning microscope at the Fralin Biomedical Research Institute at VTC in Roanoke to perform a very high-resolution microscopy of those tiny astrocyte projections that enwrap the synapses. “This new microscope will allow us to acquire a large number of images in a short time period to really dig into the questions in the study,” Olsen said.

Olsen will collaborate with two Virginia Tech researchers on this project: neuroscientists Susan Campbell, a research assistant professor in the Department in Animal and Poultry Sciences in the College of Agriculture and Life Sciences and an affiliated faculty member in neuroscience, and Michael Fox, a professor in and director of the School of Neuroscience, and a professor with the Fralin Biomedical Research Institute at VTC.

“Dr. Olsen’s work on the molecular signals that drive astrocyte maturation and the formation of synaptic astrocyte processes is fundamental to our understanding of how these specialized cells contribute to synaptic function in health and disease,” Fox said. “Her expertise in glial and synaptic biology, in cell and molecular biology, in electrophysiology, and in high-resolution imaging uniquely positions her to solve this complex question.”

It’s an expertise Olsen has developed since her first days as a neuroscience graduate student at the University of Alabama-Birmingham.

“This is where I began my lifelong love of astrocytes,” she said. “Astrocytes are the unsung heroes of the brain. They perform many underappreciated functions, but they’re fundamental to how the brain works.”

Written by Michael Hemphill

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