April 21, 2014—Before you have thought, take a step, or open your mouth to speak, thousands of neurons in your brain have talked to one another. But each of those neurons is different, Associate Professor of Biology Maria Donoghue says, and understanding more about each neuron could give us insight into a variety of neurological disorders.
In collaboration with Professor Stefano Vicini of the Georgetown University School of Medicine, Donoghue’s research lab recently published a paper in the Proceedings of the National Academy of Sciences to explain one molecule’s role in neuron development.
“The way neurons operate is one cell will send a signal to another cell [and on] to another cell, which will eventually result in a behavior,” Donoghue explained. But you should think of these cells as individuals, Donoghue says, each serving a particular role in its own part of the brain. “This paper asked how do cells attain a shape that is specific to who they are? And then, how does that shape help a cell to function properly?”
Donoghue and her collaborators found that one molecule, ephA7, had a significant effect on a neuron’s shape and function. A neuron looks a bit like a tree, with branches on the end called dendrites or dendritic arbors. “The more dendritic arbors a neuron has, the more capable it is of listening to signals from its environment,” Donoghue continued.
To learn what impact ephA7 had on a neuron, Donoghue and her team had to ask the cells what was happening when ephA7 was present or absent. And that’s where Professor Vicini and his lab came in. As an electrophysiologist, Vicini can interpret the electrical activities of a cell. The firing pattern of a cell is the distinct way it communicates with other cells. Changes in the cells’ firing patterns told the team what was going on when they added or removed the ephA7 molecule.
“First, ephA7 is guiding the branching of the dendrites,” Carrie Leonard, a doctoral student in the interdisciplinary program in neuroscience, said. “[But] it has a later role to facilitate communications with neurons,” she continued.
Donoghue and Leonard study the formation of neurons in order to better understand disorders like autism, dyslexia, and schizophrenia, which may occur due to improper brain development.
“The issue with neurological disorders is that the brain largely forms during embryonic life, but the consequences of improper function may not manifest for a while,” Donoghue said. “So it’s really hard to figure out how to approach [a disorder] because what we need to do is impact a molecule’s function before you know that it’s not functioning well.”
But the more we know about these important molecules, the better equipped we are to tackle certain neurological disorders.
This paper is the product of years of research by a team of 12 authors, including professors, doctoral students, and undergraduate students.
For Alex Russo (C’11), this research project served as a path to finding a passion and a career. Russo thought her love of science would lead to medical school, but one summer of research in Donoghue’s lab changed that, she says. After a two-year fellowship at the National Institutes of Health, Russo is now a doctoral student in neuroscience at Washington University in St. Louis. She considers the work she did on the ephA7 project as an essential part of her undergraduate education.
“From a scientific perspective, working closely with experienced and talented scientists gives an undergrad access to a kind of scientific knowledge that goes beyond memorizing names and structures,” Russo said. “I learned the fundamentals of neuroscience working in Dr. Donoghue’s lab, but I also learned how to think about neuroscience and how to critically analyze my own work and the work of others. A textbook simply can’t tell you how to do that.”
While many of the undergraduate authors have gone on to new careers, the work is not over, Donoghue says. Doctoral students like Leonard will continue related lines of research to learn more about ephA7. And those now alumni will take this research into their own careers in neuroscience and medicine.
“Any good paper raises more new questions than it answers,” Donoghue said. “And that’s the flow of science.”