Geoffrey Goodhill, PhD, professor of developmental biology and neuroscience at Washington University School of Medicine in St. Louis, has received a two-year, $675,000 grant to enhance the capabilities of light field microscopy for brain imaging. The funds, awarded by the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative at the National Institutes of Health, will go toward establishing an improved approach to visualizing cellular activity throughout the brains of larval zebrafish as they swim and hunt prey.
The system will improve on existing techniques by allowing brain imaging of freely moving zebrafish in a relatively unconstrained environment. “The system we’re setting up is a better representation of natural behavior,” Goodhill says.
Light field microscopy, a new approach developed only in the last 15 years, allows for three-dimensional, high-resolution imaging of fluorescent samples over time. Its ability to capture an entire volume of brain activity rapidly is a major advantage over other microscopy techniques. The challenge is that the field of view up to now has been small in relation to what Goodhill wants to study: the hunting behavior of developing fish.
Larval zebrafish are a favorite among neuroscientists for their transparent bodies, and at about five days post-fertilization they begin hunting their prey—in the lab setting, that’s paramecia. Using calcium indicators that signal when neurons are active, scientists have used light field microscopy to monitor all 100,000 neurons in the larval brain simultaneously as the fish swim. To do so, they developed a microscope stage that shifts location in response to the fish’s movement and thereby keeps the subject within sight. But with a field of view about 1 mm, and hunting movements that span several millimeters, Goodhill needs a bigger lens.
The R34 grant from the BRAIN Initiative will support the development of a light field microscope using a lens with a 5 mm field of view that will minimize the movements of the stage. “The fish can accelerate very rapidly,” says Goodhill. “Now we don’t have to keep up with it while it does that.”
Goodhill’s investigations of neural activity during behavior seek to answer how the brain develops neural circuitry to compute sensory input and generate behaviors. In a study in Current Biology last year, for instance, his team discovered that the progression of neural patterns during development—marked by greater cellular activity and more coordinated patterns among cells in the main visual processing center of the zebrafish brain—predicts how well an individual fish captures prey.
The light field microscopy project is a collaboration including Goodhill, James Fitzpatrick, PhD, professor of neuroscience and cell biology and physiology at WashU, and a team at Northwestern University led by the grant’s co-PI, Oliver Cossairt, PhD, associate professor of computer science and electrical and computer engineering.