By Ed Stannard, New Haven Register
Posted: 10/29/15, 1:19 PM EDT
NEW HAVEN >> Understanding the sense of smell could help in building robots to do things we rely on animals to do today, such as locating people under the rubble of an earthquake, locating illegal drugs or finding a bomb.
That’s the quest of a study at the John B. Pierce Laboratory and Yale School of Medicine, one of three underwritten by the National Science Foundation, part of President Barack Obama’s BRAIN Initiative (BRAIN stands for Brain Research through Advancing Innovative Neurotechnologies).
“There have been some studies on this problem of understanding olfaction,” said Justus Verhagen, associate fellow at the Pierce Lab and professor in neurobiology in the School of Medicine. However, “a single lab can only look at so much.”
In fact, we know “close to nothing” about the sense of smell in mammals, he said.
The team at the Pierce lab, which is affiliated with the School of Medicine, has “a mathematician, three neuroscientists. We have an evolutionary behaviorist. We have a physicist on board who actually images odor plumes,” Verhagen said.
The study will use animals such as snails, flies, mice and dogs to see how they react to an “odor plume,” which is “the concept of what an odor source looks like in space and in time,” Verhagen said.
As an odor emanates from a flower, for example, it enlarges in space and gets more diffuse, but not in a regular pattern. “It’s a little like crumpled-up paper [with] a lot of voids” where there is no odor at all.
While rats and dogs are used to find survivors underneath a collapsed building or to locate drugs in a school locker, they’re “highly unreliable,” according to Verhagen. Another application is tracing chemical pollutants in a body of water, he said.
The animals in the study will range from snails to dogs and their movements will be measured as they follow virtual odor plumes, which are created in the lab to simulate actual odors. “For example, a mouse will run on a trackball suspended on air to trace its movements and measure its brain activity as it tries to find the source of a virtual odor plume,” Verhagen said.
Also, the mice’s brains will be stimulated by light to detect how the olfactory centers in the brain respond to odors.
The projects arose from an intense workshop held in June at the Janelia Research Campus in Virginia, a farm that is part of the Howard Hughes Medical Institute. A total of 140 scientists competed for the projects funded by the National Institutes of Health.
“If you understand the problem in biology you can really apply this for the good of humankind,” Verhagen said.
Justus V. Verhagen, associate fellow at the John B. Pierce Laboratory, and Yale neurobiologist, is one of 17 researchers nationwide to receive grants totaling $15 million from the National Science Foundation to study how the brain processes and identifies odors.
The grants announced September 21, 2015 are an outgrowth of the President’s Brain Initiative and will fund three separate multi-disciplinary research efforts. Dr. Verhagen and colleagues from five other institutions will study how animals – from flies to humans – use olfaction to find resources, such as food and mates. They hope to understand how such different creatures, with such different brains, all share this ability to odor navigate.
They will use odor plume physics, neurocomputation, and behavioral neuroscience to tackle this long-standing problem. Verhagen will pioneer a virtual odor navigation task coupled with optical imaging and optogenetics.
“Olfaction is both an important and tractable problem in neuroscience,” said James Olds, assistant director of the Biological Sciences Directorate. “By using the olfactory system, which is an ancient system, as a model for neural circuits, we can gain insights into the fundamental principles underlying neural activity and complex behaviors.”
Dr. Justus Verhagen and other Neuroscientists from the John B. Pierce Laboratory and Yale School of Medicine have discovered that mice can detect minute differences in the temporal dynamics of the olfactory system, according to research published in the open access journal PLOS Biology.
The research team used light to precisely control the activity in the olfactory bulbs in mice performing a discrimination task. These “light-smelling” mice were able to detect differences as small as 13 milliseconds between the dynamics of these “virtual odors”. This approach to controlling neural activity, called optogenetics, allows for much more precise control over the activity of neurons of the olfactory system than is possible by using chemical odors.
Because olfactory bulbs exhibit dynamic neural activations in the range of many tens of milliseconds, the 13 millisecond detection limit suggested that mice should be able to discriminate these dynamics. The researchers tested this hypothesis by recording brief “movies” of the dynamic activity in the olfactory bulbs of one group of mice and projecting them back onto the olfactory bulbs of another group of naïve mice. The naïve mice were indeed able to discriminate between the movies, demonstrating that the neural dynamics of the bulb contain fundamental information about odors.
“This data is very exciting as it shows for the first time that the temporal dynamics of bulbar neural activity are meaningful to the animal”, remarked Associate Professor Justus Verhagen, the lead author on the paper. “Before optogenetics arrived as a new tool we had no means to test if this was true, we could read out the dynamic activity but could not impose it back on the brain and ask questions about its role in odor discrimination “.
These new findings build upon earlier evidence that olfactory processing in mice included temporal information about sniffs. “We knew from prior work by the team of Dr. Dima Rinberg that mice could accurately determine when their olfactory system was stimulated relative to the timing of sniffs. We now know that mice can also obtain this information directly by comparing the timing of activities among neurons. We hence think that the neural population dynamics are important for the sense of smell both independently of and relative to sniffing. Thus, a sniff can be the “start” signal from which the brain begins to analyze the times at which different neurons turn on, but the brain can also do this independently of the sniff by using the earliest neural activations themselves as “start” signals. Combined these mechanisms provide for a very robust means for the brain to use time information. But we don’t yet know how these two forms of temporal information may interact”.
Dr. Verhagen’s lab is one of several at Yale and the John B. Pierce Laboratory that are studying the neurobiology of food and flavor perception. His lab is unique in applying the power of optogenetics in mice to study the spatio-temporal capabilities of the olfactory neural circuitry that underlies these vital perceptual functions.
Source of article: PLOS Biology