As a master's degree student in Belgium in both chemical and biomedical engineering, Koen Vervaeke combined both disciplines to investigate the heart. In one project, he designed a bioreactor to grow heart valves by using the cartilage framework from a pig and a patient's own cells. The chamber mimicked the flow and pressure of blood coursing through the valve. However, he found the cardiovascular system uninspiring.
"It's basically just pumps and tubes," he says, simple engineering of this well-characterized system. "The most interesting questions in biomedical science are trying to understand the brain, the most enigmatic part of the body." So, he turned to the subject of neuroscience for his doctorate at the University of Oslo. There and as a postdoc at University College London, Vervaeke probed the building blocks of individual neurons, focusing on the ion channels that let them fire a nerve impulse and measuring how single neurons compute an input or an output—all in the confines of the petri dish.
"But I had this nagging feeling that I wanted to do things in vivo, in the intact animal. To really answer questions about how an animal senses stimuli, you have to study the brain when it is doing things it normally does," he says.
Now a Janelia junior fellow, Vervaeke uses mice to understand inhibitory interneurons, networks that act like traffic regulators of the brain, and how they are modulated by attention. Attention is part of "top-down" processing in the brain--when the brain uses things like expectations and previous experience to fill in the holes in what's happening or being seen and make sense of it. For example, if you are walking along a crowded street and see a friend, attention allows you to screen out the jumble of other, irrelevant inputs in your visual field and focus on this person's features and recognize her.
"Top-down processing is one of these things that somehow lets us interact with our environment in a much quicker manner than if we processed all the sensory information coming in through our eyes, ears, and touch," says Vervaeke.
Vervaeke wants to know how paying more or less attention to a task changes the way inhibitory neurons behave. "If information in the brain gets relayed through networks of excitatory neurons, then the inhibitory neurons are like traffic cops that can block these signals, divert them, or coordinate them."
To see how attention affects these neurons, Vervaeke has trained mice to detect a metal pole in one of two positions solely by using their whiskers--one of the mouse's most sensitive sensory organs. While the mice fix their attention on doing the task to get a reward, Vervaeke directly observes the neurons involved in the mouse's brain by peering through a microscope. The activated neurons light up with fluorescence because they harbor genetically encoded calcium activators: the more active the neuron, the higher the level of fluorescence.
He will design experiments that require either more attention to the task (e.g. the two positions of the pole are very close together) or less attention (far apart) to track where attention comes into play in the barrel cortex of the mouse brain, the area that processes sensory information coming in from the whiskers.
Vervaeke hypothesizes that the interneurons are modified by attention and figuring out how attention changes the perception of sensory information could lead long-term to a better understanding of disease states with disrupted attention, such as Alzheimer's disease, dementia, and attention deficit disorders.
"Very few people study attention on the cellular or circuit level," he says. "To show a link between attention and the properties of cells requires specialized technology such as the fluorescent calcium activators that only a few labs in the world have." He calls Janelia Farm "the best possible place" to do his research. "The whole institute is focused on the level of the brain I'm interested in and scientists here have developed the technologies needed to get at these questions."
