The National Institutes of Health (NIH) has given Tim Holy, Ph.D., an NIH Director’s Pioneer Award — one of only 18 given this year — to develop innovative ways to monitor the activity of many neurons simultaneously.
The NIH Director’s Pioneer Award funds “individual scientists of exceptional creativity who propose pioneering – and possibly transforming approaches – to major challenges in biomedical and behavioral research,” according to an NIH Web site.
Holy, associate professor of neurobiology at Washington University School of Medicine in St. Louis, studies how the male mouse brain responds to female mice pheromones, which are chemical signals related to mating. He uses what he learns to build a foundation for understanding how pattern recognition and learning take place in the much more complex human brain.
Holy has previously won recognition for his innovative approaches to monitoring neurons. In 2008, he received the McKnight Endowment Fund for Neuroscience’s Technological Innovations in Neuroscience Awards for development of an approach known as objective-coupled planar illumination microscopy (OCPI).
“The challenge at that time was that neurons do their computations on millisecond time scales, and our techniques for monitoring those computations in more than one or two neurons were taking about a second,” says Holy.
To create OCPI, Holy’s lab devised a new way to shine laser light that only illuminated the neurons of interest, allowing scientists to monitor the activities of many neurons much more rapidly.
Many techniques for monitoring nerve cell activity, including OCPI, add dyes to the neurons that fluoresce in response to laser light. With the Pioneer Award’s support, Holy hopes to find a way to take the dyes out of the picture.
“When we look at the same neurons over and over again, which many scientists want to do, we run a risk of what’s called photobleaching,” Holy explains. “Not only do the dyes start to lose their ability to fluoresce in response to the laser, there’s also a danger the reactions that drive fluorescence will create free radicals that can damage or destroy the cells or important proteins inside them.”
Holy says scientists already are considering several signals not linked to the addition of fluorescent dyes that could be used to monitor nerve cells. But new approaches are needed to be able to image those signals in intact brain tissue.
“The advantage of what we’re hoping to achieve would be to be able to monitor the activity of large populations of neurons at high speed for long periods of time,” he says. “It won’t give us the same level of detail as other techniques that only focus on one or two neurons, but it will allow us to develop a much better picture of how communities of nerve cells work together.”
The award will provide Holy with $500,000 annually over five years.
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.