Scientists in America have created the first detailed map of the smell receptors in the nose. The study builds on similar achievements in sight, hearing, and touch, and the findings – which have been published in the journal Cell – may in the future help develop better therapies for people with loss of their sense of smell – anosmia – or damage to it, a state called parosmia. Bob Datta is a neurobiologist at Harvard Medical School, and he’s been speaking with Chris Smith…
Bob – Odours are small, volatile chemicals that we sense through our noses, and they’re detected by specialised molecules called odour receptors. And so, you can think of odour receptors as being like locks and odours as being keys. And so, when a key matches to its lock, it turns and the receptor will become activated and that allows the nose and eventually the brain to know what it is you’re smelling. And the question we really wanted to understand was, are there different patterns of receptor expression in your nose creating a map for smell?
Chris – Did previously people think it was just a sort of mosaic then that these receptors that detect things just randomly scattered all over the top of the nose where we do smelling and when a certain smell goes up your nose, those receptors fire off and you say, oh, I can smell that. Or did we have some insight, an instinct that perhaps there would be clustering of molecules that detect this group of smells or in one place versus molecules that detect other or receptors that detect other smells are in this place? What did we think?
Bob – Yes. So the initial sense from the 35 years of work that people have done trying to figure out whether there’s a pattern of receptor expression in the nose, largely supported the model in which receptors were kind of randomly scattered about in your nose. I think that’s important to realise is that we have a lot of these receptors. In humans, we have about 400 different receptors. And in mice, the subject of our study and the organism in which I work, there are about a thousand different receptors. And so there’s so many of these receptors, no one thought it was possible to even build a map out of so many different things. And so people thought that maybe the sensory neurones in your nose, the cells that are responsible for detecting smells were just kind of randomly choosing which receptor to express. And so there was a kind of random mosaic, which means that my nose fundamentally is organised slightly differently from your nose.
Chris – How then have you pursued this to try and work out what the map if it’s there might be?
Bob – Modern technologies let us look at which receptors and other genes are expressed in single olfactory sensory neurones, cells in your nose that allow you to smell. And taking advantage of that technology, along with new mapping technologies that let us look at where receptors are in different tissues, we were able to map spatial positions of all 1,000 of these receptors very precisely in the mouse nose. And that revealed a surprising map.
Chris -So, there is a pattern?
Bob-There is a pattern. It turns out the pattern is going from the top to the bottom of your nose, there are a thousand different stripes, which have precise positions. And each one of these stripes corresponds to a particular odour receptor. So the odour receptors that are at the top of your nose are very different from the odour receptors that are in the middle and different from the ones that are at the bottom. And critically, the ordering of these thousand stripes was the same across all 350 mouse samples that we looked at. And so, what that means is that it’s very likely that my nose is actually organised in the same way as yours.
Chris – It’s good to know – or nose. But how is that achieved then? And why does nature go to the trouble of doing that? What’s the advantage of organising stripes of different zones of chemical detection like that?
Bob – No one believed that the nervous system was capable of organising a thousand things so precisely. So, the fact that it does is a kind of miracle in and of itself. Then, given that we have this map now, the question is why is the map organised the way it is? I can tell you many possibilities, all of which we’re working on in the lab today. One possibility is that maybe different aspects of odour chemistry are encoded in this map. So maybe alcohol molecules, like in beer, maybe those are detected at the top. And maybe sulphur molecules, like in natural gas, maybe those are at the bottom. Another possibility is that maybe odour categories are organised in space. Maybe citrus is at the top, and meat is at the bottom. Or maybe odour meaning is organised in the map. Maybe things you like are at the top and smells you hate are at the bottom. Any one of those things is possible. We’ve just begun to scratch the surface of this map. We think that some aspects of odour chemistry may live in this map. There’s a lot of work left to do before we really understand what the map means.
Chris – The other intriguing thing is that different molecules that are very good at binding onto their receptors versus ones that are not very good at binding onto their receptors, they’re better detected when air goes faster or slower. So, does the positioning of the receptors also get dictated by how fast the air is moving or how much air is moving over that patch of the nose that does the smelling for those molecules?
Bob – Oh, that’s such a wonderful question and actually one of the things that we’re looking at. Another way you can think about what you just said is that there’s some lighter molecules, some odours that are really light and volatile, like ammonia, and there’s some heavier odour molecules, like the scent of fat, for example, and maybe based upon airflow and the weight of odour molecules, different receptors are differently positioned to optionally detect molecules of different weights and volatilities in the context of airflow and that’s definitely something we’re looking at right now.
Chris – So if I compare, say, a dog, which a dog’s sense of smell is way beyond the resolution of ours. Obviously, that’s why we use dogs to go and find things and people and so on. When you add more resolution like that and more smelling ability, have they basically got the same pattern, but it’s just got more receptors or a wider spectrum of receptors or is the organisation different, do you think?
Bob – So I think it’s probably true that the organisation itself is a little bit different. Humans have 400 receptors, mice have 1,000. Many dog species have 2,000 different types of receptors so they really do have much more resolution over the odour world when compared to us or even mice and so it’s likely that they not only have more receptors but those receptors are placed in a different order in their nose and that might help them detect different types of smells and organise information about smells a little more effectively than in us.