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Spencer Smith

UNC neuroscientist earns NSF grant to build a better way to explore the brain

UNC School of Medicine neuroscientist Spencer Smith, PhD, received a $300,000 National Science Foundation Early Concept Grant for Exploratory Research (EAGER) to develop a two-photon microscope capable of recording the activity of individual neurons in multiple areas of the brain at the same time.

The technology will allow Smith, an assistant professor of cell biology and physiology, to observe active neural circuitry in the visual cortical areas of living animals. It will allow scientists to see which neurons – and which kinds of neurons – fire as a result of visual stimuli or specific behaviors of the animals.

“If you want to understand how the brain works, we have to be able to look at a more systems-level view of neural activity.”

“Right now, we don’t really have a good idea how that happens,” said Smith, a member of the UNC Neuroscience Center. “If you want to understand how the brain works, we have to be able to look at a more systems-level view of neural activity. We think it’s this type of technology that will give us the insights we need to advance our understanding of how brain circuitry actually works, not only in normal circumstances but in disease states.”

For instance, scientists have made significant advances in understanding the pathology of certain brain disorders by linking a gene to a molecule and then to the faulty activity of synapses between neurons. But, Smith said, what happens to neural circuitry throughout the brain during these diseases remains poorly understood.

“Down the line, we hope to address this with this new technology,” Smith said.

Smith, whose most recent research was featured in the journal Nature, is not new to designing microscopes. His first two-photon microscope allowed him to view individual neurons firing in the brain of a mouse over an area of 1.4 millimeters. His team then designed a system to view individual neurons firing over a span of 3.5 mm.

“But we really need to optimize the optics on that microscope before we can use it,” Smith said. “This is what the NSF grant is supporting.”

Typically, when scientists want to build a microscope, they buy the lenses off the shelf. Smith, though, couldn’t find what he needed. “And the custom design process was extremely slow and expensive,” he said. “I figured we’d see if we could do this ourselves.”

He enlisted the help of Jeffrey Stirman, PhD, a postdoctoral fellow and bioengineer in his lab, and Mike Kudenov, PhD, an optics expert at NC State. The team designed precisely what Smith knew he’d need to increase his field of view in the visual cortex while also improving the resolution of the images of the neurons. Smith’s lab is currently building the new microscope, including developing custom optical systems.

“It’s as if you’re developing a high performance car; typically you’d find a nice engine to put in it,” Smith said. “You wouldn’t think about buying a hunk of aluminum and start drilling to make the entire thing from scratch. But that’s sort of what we did to make the objectives for the microscope – the actual glass lenses that we needed in order to get the performance out of the microscope that we want.”

Smith plans on finishing the construction of the microscope in the next two years with the new grant support.

The NSF issued 36 EAGER grants to researchers working to create technologies that will allow scientists to better understand how complex human behaviors result from neural activity inside the brain. The grants, totaling $10.8 million, were made in support of President Barrack Obama’s BRAIN Initiative, a multi-agency endeavor with the goal of creating new neurotechnologies to help scientists open new areas of investigation into how the brain works.

Read more about the NSF EAGER grants.