Scientists win grant to study brain's role in tracking odors

Seeking to unravel the mystery of how animals follow scent, a team of scientists from the University of Colorado Anschutz Medical Campus, the University of Colorado Boulder and Columbia University, have won a grant to peer deeply inside the brain as the process takes place.

The $ 2,990,152 award is the second that the group has received. The two grants total $5,984,351 and are part of the National Science Foundation and National Institutes of Health's BRAIN Initiative, an effort to better understand the intricacies of brain function.

In this case, scientists hope to divine the neural circuitry underpinning the often-extraordinary ability of some animals to track scent.

Despite vigorous research, the algorithms used by organisms to navigate the odor plume remain mysterious. Exactly how the brain solves this complex sensorimotor task that is key to escaping, mating and eating is unknown."

Diego Restrepo, PhD, Neuroscientist at CU Anschutz

Diego Restrepo leads the team that won the grant.

Studying this in the natural environment is challenging due to the vastly different scales on which animals use their sense of smell. Everything from microbes to mammals follow scent plumes to some degree.

So the scientists formed the Odor Plume Neurophotonics (OPeN) interdisciplinary team, encompassing engineering, environmental science, computational science and neuroscience to better understand how it works.

CU Boulder Environmental Engineering Professor John Crimaldi, PhD, will design a portable device to measure odorant concentration at the nostrils as the animal tracks the odor plume in the dark.

Emily Gibson, PhD an associate professor in Bioengineering at CU Anschutz, developed a three-photon microscope that uses longer wavelength near-infrared light to allow much greater imaging depth in living tissue.

Now Gibson, together with Professor Victor Bright, PhD, and Associate Professor Juliet Gopinath, PhD, of CU Boulder and Professor Ionnis Kymissis, PhD, of Columbia University will develop a miniature fiber-coupled, three-photon microscope. It will fit atop a live mouse's head and record neural activity from multiple deep brain areas including the hippocampus and cerebellum as the mouse navigates the odor plume.

The microscope uses a unique liquid lens, called an electrowetting lens, to achieve dynamic focusing in deep tissue for 3D images.

"The electrowetting technology enables a truly adaptive, compact miniature microscope," said Bright and Gopinath.

Professor Restrepo and Associate Professor Abigail Person, PhD, of CU Anschutz, will use this information to test the hypothesis that as animals navigate odor plumes in the dark, the cells in the cerebellum and hippocampus develop a map of space and odor location with information that can predict a mouse's approach to the source of the odor.

Restrepo believes the results will reveal new aspects of brain function and lead to further studies into more complex natural environments with multisensory cues and moving odor sources.

"There is so much we don't know," he said. "How does a dog sniff out explosives? How does the brain solve this? Here we will be able to watch neurons firing as the animals navigate toward the source of the odor and use computational analysis to put it all into perspective."

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