The Neuroscience of Following Your Nose

Keck Professor Gautam Agarwal’s Nature article reveals how part of the brain draws on sense of smell to create spatial maps

Claremont, Calif. (January 4, 2022)—Assistant Professor of Neuroscience Gautam Agarwal seeks to make sense of complex interrelationships in the brain. His latest article, “Spatial maps in piriform cortex during olfactory navigation,” sheds new light on an under-explored region of the brain and its role in odor-guided navigation. Co-authored with Cindy Poo, Niccolò Bonacchi, and Zachary Mainen of the Champalimaud Centre for the Unknown in Portugal, the article was recently published in the scientific journal Nature.

Neurons in the primary olfactory cortex create an odor-spatial map. Credit: Diogo Matias, Champalimaud Foundation

“Odor molecules do not inherently carry spatial information. However, animals in the wild use odors for spatial navigation and memory, which allow them to locate valuable resources such as food,” said Cindy Poo, the study’s first author, in a Champalimaud Centre press release. “We wanted to understand the neural basis of these behaviors, and so we decided to study how the brain combines olfactory and spatial information.”

Agarwal, who teaches at the W.M. Keck Science Department of Pitzer, Scripps, and Claremont McKenna Colleges, and his co-authors studied the primary olfactory (piriform) cortex, which is tucked deep in the brain. Part of the olfactory tract, the piriform cortex has been thought to be dedicated to encoding odor identity, essentially linking mental associations with specific smells.

When you smell something, the odor activates the olfactory bulb, which Agarwal says is to smelling as the retina is to seeing. The olfactory bulb shoots info on the odor directly to the piriform cortex—unlike other senses, smell has no intermediatory like the thalamus between it and the cortex.  

Agarwal, who is a computational neuroscientist, partnered with experimental neuroscientist Cindy Poo at the Champalimaud Centre in Lisbon to analyze data on the posterior piriform cortex she collected through a series of experiments with rats.

The posterior piriform cortex sits next to the hippocampus, a centerpiece of the brain that plays a critical role in memory and learning as well as navigation and a sense of where you are in space. Given its position deep in the central folds of the brain, the posterior piriform has been explored less than other regions—“The deeper you get in the brain, the less you know about what’s going on,” Agarwal said.

To figure out what’s going on, Poo used “neural ensemble recordings in freely moving rats performing a novel odor-cued spatial choice task”—essentially, she created an experiment in which rats poked their nose in one of four ports of a plus-shaped maze. The port would then release one of four odors, and each odor pointed the animal to a specific destination where it could collect a reward. Over time, the animal had to learn which smell indicated which destination port.

“It’s a hybrid between an olfactory task and a navigation task,” Agarwal said.

Agarwal, who uses mathematical tools, including machine learning, to analyze huge data sets, joined forces with Poo to try to make sense of the “zoo of data” she had collected from almost one thousand cells in the brains of three rats. They wanted to find out how well this brain region responds to odors, and how well it responds to space.

What they discovered in the data surprised them and other scientists—and intrigued Nature, considered one of the leading peer-reviewed scientific journals in the world.

“The initial surprise was that the sense of space is more prominent in this brain region than the sense of odors,” Agarwal said. “That’s weird, because it’s part of the olfactory stream and part of the brain region that is nominally connected to olfactory bulb.”

Why would a part of the sensory cortex be so involved in navigating space? Because it’s sitting next to the hippocampus, its next-door neighbor that influences our sense of spatial relations.

While it was surprising to find evidence that this olfactory brain region cares about space, the results fit with a relatively recent understanding of how the brain works, Agarwal said. Instead of thinking of brain regions being predominately driven by external stimuli—an odor hits the olfactory bulbs, which “lights up” cells in the olfactory brain region—neuroscientists are seeing brain regions as carrying on a dialogue between what’s coming in from the outside world and our mental models of the world.

In the brain region they studied, the authors put it this way in the Nature article: “Ensembles of piriform neurons concurrently represented odor identity as well as spatial locations of animals, forming an ‘olfactory-place map.’ Our results reveal a previously unknown function for piriform cortex in spatial cognition and suggest that it is well-suited to form odor-place associations and guide olfactory cued spatial navigation.”

How does this translate into the way we move through the world? When using smells in navigation, animals usually follow their nose to get to the source—from A (the smell) to B (the cheese). This brain region seemed to be doing something slightly different.

“This brain region might be responsible for a different kind of olfactory navigation: following your inner concepts of where a given odor is coming from,” Agarwal said. “Unlike the hippocampus which has a general map of space, this map seems to really care most about the sources of odors and the sources of rewards associated with the odors.”

If you get a whiff of baking cookies, Agarwal said, you know that cookie is being made in the kitchen, even if you don’t follow your nose to the source. You’ve learned from previous experience cookies are baked in the kitchen.

“There’s a conceptual map that associates different odors with different sources.”

There are still a lot of unknowns and more work to be done, Agarwal said, but these findings shed light on a largely uncharted territory in the brain. In this area of research, scientists are essentially “spelunking” into a new brain region to try to make sense of what’s going on there, Agarwal said.

“So that’s exactly what this study represents—going into a new brain region that is currently uncharacterized,” he said. “We’re in a very new and exciting field.”

Professor Gautam Agarwal
Gautam Agarwal, assistant professor of neuroscience, Keck Science Department

Gautam Agarwal joined the Keck Science Department in 2021. Originally focused on experimental neuroscience, he switched to computational neuroscience to explore how we can use the formal language of math and aspects of machine learning to gain deeper insight into how the brain works. Agarwal earned his BS in molecular biology and computer science at the University of Texas at Austin and his PhD in neuroscience from UC Berkeley. He completed his postdoctoral work at the Redwood Center for Theoretical Neuroscience at UC Berkeley and the Champalimaud Centre in Lisbon, where he developed a video game to study the structure of insight-driven problem solving and its diversity across human populations. 

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