How Do Our Brains Keep Smells Organized?

IRA FLATOW: This is Science Friday. I’m Ira Flatow. A sense of smell is a bit of mystery. Is it not? Even for scientists. We know what a color will look like based on its wavelength. Every color has a predictable signature.

But predicting the smell of something? That’s a bit more difficult. For example, think of a sea-breeze-smelling candle. Does it really smell like the sea? I mean, how can the ocean be in a candle? But once you sniff that candle, you are transported to the coastline and that wafting breeze, yes.

How does our brain keep track and organize the millions of scents that we sniff? That’s what a group of scientists wanted to find out. They gave mice molecules to smell and tracked what patterns were formed in the brain. Their results were published in the journal Nature, and here to talk about it is one of the authors on that study, Robert Datta. He’s an assistant professor in the Department of Neurobiology at Harvard Med School joining us to talk more about how we sniff out smells. Welcome to Science Friday.

ROBERT DATTA: Hi, how are you?

IRA FLATOW: So tell us why has the sense of smell been so elusive to scientists?

ROBERT DATTA: There’s a couple of reasons. One is that smells are really, really complicated. If you think about the odors that are coming off your morning coffee, that scent is actually made up of more than 800 separate, individual molecules, and somehow your nose recognizes all of those different molecules. And your brain synthesizes that into the delicious smell of coffee in the morning. And so because of the complexity of odors themselves, for a long time we’ve had– there have been challenges in our understanding how the brain might organize information about different odors that makes scents.

IRA FLATOW: That is really cool. You were studying mice, and you gave them some odor molecules. Give me an idea of what you were looking for in the brain afterwards.

ROBERT DATTA: So we do experiments where we use microscopes to look at neural activity in a part of the brain that’s responsible for processing information about smells, and it’s part of the brain called the piriform cortex. We as humans have a piriform cortex just like the mice, and we were looking to see what different patterns of activity emerge as we gave these mice different kinds of smells.

IRA FLATOW: And is there a definite pattern of activity, and is it located in a certain part of the brain?

ROBERT DATTA: Yes, there definitely is. Our goal in this study was to answer two main questions. So first, we wanted to understand why is it that you and I, Ira, both think that lemon and lime are similar to each other? We both agree that lemon is different from pizza.

And the second thing we wanted to understand was why is it that smell seems to be so personal? Why do we– why do I think that the way that I interact with the odor world might be a little bit different from the way that you interact with the odor world.

So the thing we want to look for first was whether the patterns of activity we saw in this smell center in the brain, called the piriform cortex, were similar in me and you. And what we discovered was that the relationships and the patterns that are evoked by similar odors themselves tended to be similar. So lemon and lime activates similar patterns of activity in my brain, and they activate similar patterns of activity in your brain. And that’s why you and I both agree that lemon and lime are two similar odors.

But if we expose a mouse to different odors, we can actually change the relationships between patterns of activity that we observe in the brain, and we change the way that animals perceive those odors. And so although you and I both agree that lemon and lime or similar based on our odor experience, the way that we interact with odors in the world, our brain is clearly flexible and plastic and capable of changing the way that it represents information about odor relationships to support our perception of different odors.

IRA FLATOW: This is all interesting, because we all have a time where it could be 10, 20, 30, who knows how many years later where suddenly you have a– you smell something you haven’t smelled for decades, and then this memory just comes right out. What’s going on there?

ROBERT DATTA: Yeah, so one of the interesting things about smell is that it was the first sense really to evolve. It’s the most ancient sense we have as mammals. And so the neural circuits that are responsible for processing smell are organized in a very different way from those of the other senses.

So if you were to ask me how many neural connections does it take to get from your retina when you see something to a part of your brain that’s involved in memory like the hippocampus, that number is really large. It’s like 10 or 20 interconnections between your eyeball and a part of your brain that’s responsible for memory or say emotion.

In olfaction, that number is two, so information about smells goes to your nose. There’s one processing station in your brain called the olfactory bulb, and then immediately it goes to parts of your brain involved in memory, while the hippocampus are involved in emotion like the amygdala.

And so there’s is very intimate brain connection between smells in the world and your emotional responses to those smells and your memories that are also associated with those smells and when you experience those smells. And part of the reason why my lab is so fascinated with smell is because of this really intimate connection between these emotional and memory centers in your brain and the world of smells around us.

IRA FLATOW: How do you train somebody to know what should something should smell like or shouldn’t?

ROBERT DATTA: So there’s really two parts to this process. One is gaining language for describing what you’re smelling. We as humans, depending on our culture, use very different language to describe different kinds of smells. And the parts of our brain that are responsible for generating language are actually very far separated from our noses, unlike our centers for emotion and memory.

So although when you smell a scent from your mom’s kitchen, it can evoke this deep memory. You’ll often have trouble finding the words to describe what you’re smelling. And so part of what training gives you is just language to accurately describe what you’re perceiving.

But it’s also quite clear that as you gain more and more experience with odors, your olfactory circuits are quite plastic. And they will readily learn to better discriminate and categorize odors. It’s actually part of what our papers about is thinking about how odor circuits discriminate and categorize odors, and it’s clear that the olfactory system is really wonderful at addressing both of those questions and those problems and is capable of learning based upon experience.

IRA FLATOW: Well then tell me– I’m bringing you– I’m bringing this back to where I started about light. If we know the certain frequency or wavelength of light, we can create the exact color we want. Can we do that with smells? Can you put a molecule together that gives you the exact smell that you want?

ROBERT DATTA: You’re asking a fabulous question, and this is really a longstanding dream of people who are interested in the olfactory system. Wouldn’t it be marvelous if we knew enough that we could construct an artificial molecule and before even smelling it, know what it was going to smell like. This is something that’s not yet possible.

We’re just beginning to learn how chemical structures relate to patterns of neural activity in the brain, which is of course part of what our study was about, and understanding our relationship, understanding how chemistry evokes different patterns in your brain. It’s really the first step towards building some sort of machine that will allow you to predict what a specific odor chemical will smell like.

And you can imagine that if you could build such a machine, that would amazing in terms of helping people make tastier foods or more attractive fragrances. And it would also allow you to virtualize smell. You can imagine that instead of just having a virtual reality being visual, you could have olfactory virtual reality, where there were machines that were in front of you that would spit out chemicals that you would smell in real time that would evoke various known odor perepts.

IRA FLATOW: Aroma therapy.

ROBERT DATTA: Exactly, exactly.

IRA FLATOW: So I’m imagining there must be some connection between our taste buds, what we taste and when we smell, because the old saw says that what you’re really tasting, you’re doing a lot of smelling.

ROBERT DATTA: Yep.

IRA FLATOW: So is it wired into your brain that way too?

ROBERT DATTA: Yeah, so flavor is thought to be the combination of smell and taste. And when you chew food up, the food gets of mushed up in your mouth, and then odors release from the food. And you detect those odors. There’s something called retronasal olfaction. That is, the stuff that’s coming off of your food goes up into the back your nose, and you smell it. And your brain then synthesizes information from your taste buds and from your olfactory neurons in your nose in a part of your brain called the insula to create perceptions of flavor. So those two things are really intimately linked, and if you lose your sense of smell, as you know, all of a sudden the flavor in your food disappears. That’s what happens when you get a cold.

IRA FLATOW: Well that brings me to the question about what’s going on with COVID-19 and losing smell. How are these things related?

ROBERT DATTA: Right, so it turns out my laboratory has also recently published a paper along with an international consortium of researchers exploring how it is that COVID might affect your sense of smell. As I just told you, odors in your nose are detected by these olfactory receptor neurons that express odor receptors. These receptors interact with the odors, and then these neurons alert your brain to what you’re smelling at any given moment in time.

And so, I think, we and many others started with a hypothesis that maybe the virus infects these olfactory sensory neurons and damages them or kills them in some way. And that’s how come when you get COVID, you’ll lose your sense of smell. But the emerging data from our lab and the labs of our many collaborators really suggests that instead what’s probably going on is that novel Coronavirus is infecting support cells that live around these olfactory sensory neurons.

And so somehow through infecting these support cells, your neurons in your nose stop functioning properly, and so you can’t smell odors anymore. And we actually think this is pretty good news, because it suggests that people with COVID who lose their sense of smell will eventually regain their sense of smell once these support cells have regenerated and heal.

IRA FLATOW: That is good news. As someone whose job, and sounds like passion, is sleuthing and smelling everything– smelling all the roses along the way, do you drive people crazy stopping to smell stuff?

ROBERT DATTA: I do. Especially when I go to– when I go shopping, I cannot stay away from the perfume counter. Some of my inner moments– some of my inner moments are discovering new smells just out in the environment. It’s fun to study a scent that I find really personally very satisfactory.

In science it’s called “mesearch.” You do research on the thing that you yourself find most interesting. And for me this has definitely been quite a bit of “mesearch.”

IRA FLATOW: That’s great that you enjoy it, and maybe someday one of these perfume companies will name something Datta after you. You never know.

ROBERT DATTA: You never know.

IRA FLATOW: Thank you, Robert. Robert Datta is one of the authors of a study in Nature about the smells. He’s also assistant professor in the Department of Neurobiology at Harvard Med School, and I want to thank you for taking time to be with us today.

ROBERT DATTA: Thank you very much.

IRA FLATOW: I’m Ira Flatow. This is Science Friday from WNYC Studio.

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