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Cracking the Olfactory Code

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Cracking the Olfactory Code

Oct 27, 2015

We’re all familiar with the power of smell: a Thanksgiving turkey roasting in the oven may lure you into the kitchen, while the stench of rotting trash can cause you to run the other way. However little is known about how odors can trigger very different neurological responses and behaviors. Matt Wachowiak, USTAR professor of neurobiology and anatomy at the University of Utah is collaborating with a large, interdisciplinary team to crack the olfactory code. Wachowiak explains the barriers he and his team are facing, how they are approaching the problem, and what they hope to accomplish.

Episode Transcript

Interviewer: Cracking the olfactory code up next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Interviewer: I'm talking with Dr. Matt Wachowiak, a USTAR professor of neurobiology and anatomy at the University of Utah. Cracking the olfactory code. What does that mean?

Dr. Wachowiak: The goal is to really understand how the brain figures out what it is that we're smelling. What's happening in the brain when the animal smells that odor, and how does that get translated into some sort of perception and some sort of behavioral output.

Interviewer: Give me some examples. What are some smells that might trigger very different reactions?

Dr. Wachowiak: The smell of good food or the smell of wine generally triggers some positive emotions, some positive responses. We want to drink, we want to eat. Kind of another side of that would be the smell of smoke for example or the smell of rotting food. We get a very different visceral response to that kind of odor.

We want to basically go in the other direction. That's one of the most simple dichotomies that we can make about odors. Of course odors are very, very complex in terms of their perception. There's a huge amount of information that we take out of odor beyond just good and bad.

Interviewer: Why do you think it's important to understand this code?

Dr. Wachowiak: Just in terms of using this as a system to understand how the brain processes information I think it's really important to understand olfaction because it's so complex as a sensory problem. It's very different from any other sensory modality, for example vision or touch or hearing, simply because we're detecting molecules from the air and they come in a huge range of different structures. They're not organized in a very clear way the way light for example is or sound.

It's just a very different problem that the brain has to solve and we don't understand much about how the brain solves that problem. Just as a way of getting new insights into how the brain processes complicated information, I think it's really important to study olfaction.

Interviewer: Give me a sense of the scale of the problem you're facing.

Dr. Wachowiak: This is really one of the challenges with olfaction and why it's one of the most complex senses and still one of the least understood, mammals like mice and rats which have very well developed sense of smell. They have about a thousand receptors. It's actually the largest gene family in the genome. Odorant receptors make up around 3% of the entire genome.

Interviewer: Wow. Really?

Dr. Wachowiak: Yes. But the real problem is what we don't know. We can identify these genes by looking in the genome, but what we actually still don't know for any given gene what odors the receptors actually detect. This is the major problem. So this is one of the goals of our group is to actually do what's called "deorphanization" which is to identify for every receptor what are the odor molecules that that receptor best detects.

It's been a really hard problem just for technical reasons. So one part of our group has really made some important breakthroughs in the last couple of years in terms of being able to screen receptors for many, many odors and be able to identify the odors that are activating particular receptors. That's one important part of the project.

Interviewer: I imagine it's not that there's one odor for one receptor.

Dr. Wachowiak: The receptors can be activated by many odors, another big part of this problem is that there are so many potential odors out there in the environment. The number of compounds that smell, that we can smell is easily in the thousands. There have been some estimates that are orders of magnitudes higher than that in the millions. That's debatable, but the number of compounds that are volatile that receptors might be able to detect is huge.

Another ambitious part of this project is to really screen a fairly large number of compounds. We're going to screen 1,000 different odors across all the receptors. The goal is to first deorphanize all the receptors using this panel of 1,000 odors.

So then we'll have for a given receptor not just one compound that might activate that receptor or one odor, but we'll be able to make or give a spectrum of tuning curve. So this odor works better than the other odor and we can put those in a response spectrum is what we would call it.

Interviewer: But you're taking it beyond that as well.

Dr. Wachowiak: What we need to know is how does the brain process that information. What does that code look like as we get in to the brain. One goal that we're going to work on is to then be able to assign the identity of the receptor to the glomeruli in the olfactory bulb and we can do this in the intact animal.

We have ways of using an imaging approach where we can literally look at fluorescent proteins that are expressed in these cells in the brain. We can look in the intact animal and watch activity happen basically with imaging and so then we can follow what happens as we go from sensory neurons into this first stage of the brain.

Interviewer: Are you tracking behaviors as well?

Dr. Wachowiak: Yes. That's another part of the project. Right now we can identify odors that seem to be intrinsically aversive that the animals will avoid. A great example is the odor for mice, a great example is the odor of predators. Big cats for example. Urine of big cats they will avoid intrinsically. Even a mouse who has never encountered a cat. And of course they're attracted to compounds that are coming from other mice for example. We can map this behavior.

We're studying the olfactory bulb. Certainly the information from the bulb goes farther into the brain into parts of the olfactory cortex and the part of the brain called the amygdala which is thought in many different contexts to be really important in emotional responses and to all kinds of stimuli.

A hope would be we could then look at a given odor or maybe look at a given pattern of activity. Look at a given receptor even and be able to predict what's going to be the innate behavioral response to that and maybe even what's the pattern of activity going to look like in the brain.

The goal is to understand how does the brain understand information. How does it generate behaviors. We need to look at all aspects of that. Again, olfaction is one of the most important senses for driving behaviors in most animals even in most mammals. We're really trying to use that system to get some insight there.

Announcer: Interesting. Informative. And all in the name of better health. This is The Scope Health Sciences Radio.