How does smell work in the brain?

20 July 2019

Interview with 

Elisa Galliano, Cambridge University

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What actually is a smell? And how does it get into the brain? Katie Haylor sniffed out the science with neurobiologist Elisa Galliano from Cambridge University...

Elisa Smell is what we perceive in our brain. It's not so much a chemical molecule, a chemical substance; it's the way in which our brain makes sense of all the chemical substances there are in the environment around us. We need to first detect them - there is a part of our nervous system that will recognise them - but then we need to make sense of them. There is specific molecule that makes the smell of banana, for instance; from there to the concept of banana there is quite a lot of processing that needs to happen in the brain, and that's what we call a smell.

Katie - So say a bit of banana gets into the air, it floats across, it wafts around your nose... how does that actually get to your brain?

Elisa - In the nose there are specialised neurons called olfactory sensory neurons. These are very, very long neurons. They have some sort of tentacles called cilia, and this is where the bit of banana gets stuck and activates this neuron. They become overexcited and they send this information like, "look, there's banana," down into the brain. This information about banana gets processed by different brain areas. The first one is called the olfactory bulb which sits at the bottom of your brain ready to receive information from the nose, and then there are other areas in the cortex, specifically the piriform cortex. And where all these neurons in this area do their processing and their work, there in the piriform cortex is probably where the concept of banana, the idea of 'banana' starts taking place.

Katie - So in order to get these electrical impulses rocketing up into the brain, does that mean there are specific receptors for specific smells? Because there's a lot of smells...

Elisa - That's exactly right. And if you can think of smells like keys and the receptors as locks, there are lots of keys and so we're gonna need lots of locks. And those are the ones that are expressed in the epithelium in the nose. And each single person expresses a completely different set of them. So not every single nose is the same. Genetic variation and mutations, events that happen in your life, can really change the composition of your nose. So that's why the same chemical, the same substance, does not necessarily smell the same to different people.

Katie - So could that explain why for instance I love banana, but I know one of my friends detests it and will actively leave a room if someone is eating a banana?

Elisa - Absolutely. So your friend could have a different set of receptors, but also - and this is very important - the smell, being a perception, is very tightly linked to our emotion and experience of the first time that we were introduced to banana. Probably you were given banana by a teacher, or one or your parents, and they told you that it was yummy and it was quite sweet, and it was a good day. But if your friend for instance who had the same receptors as you, or similar, ate the banana and then immediately after had terrible stomach flu; and then this idea of banana becomes tightly linked to a very unpleasant feeling and the smell will bring back this unpleasant feeling.

Katie - So there's the detection of the chemical or the chemicals, and then there's how the brain interprets that information. And what you're saying is those are two different things, right?

Elisa - Very different. The detection happens in the nose by these olfactory sensory neurons, and the perception happens higher up in the brain. And because those areas in the brain are very closely related to the areas of the brain that encode for emotions, and associations, and memory... that is why odours have such powerful emotional attributes to them.

Katie - Now I believe I have a better sense of smell than anyone else in the Naked Scientists office. I've been referred to as a bloodhound, and I want you to put me to the test. So what exactly have you got, this contraption that's sitting in front of us?

Elisa - This was a task that was developed by my colleague Dan Rokni when we were both in Venki Murthy's lab at Harvard University. We do this with mice. I'm gonna ask you to smell a small bottle which contains a pure chemical, one single odour, and you're going to have to learn it and remember it. And then you're going to have to go through the rack of smaller bottles. Some of them could contain the odour I asked you to remember and some may not contain it. But to make it even more difficult, some bottles that I'm going to ask you to smell will contain only one odour. Other bottles will contain up to five. And I want to see... if you think you're a bloodhound you should be able to spot your remembered odour even in this more messy situation.

Katie - Feeling a bit intimidated now. But this is a bit like an olfactory cocktail party, right? My task is to differentiate a combination of smells - rather than voices in a loud room - and I need to pick out one particular smell from many. Is that the idea?

Elisa - Yes, that's the idea.

Katie - Okay, well I'd better smell the target smell then.

Elisa - There we go.

Katie - It's really nice! It's quite sweet. Okay, I think I've got it. It's kind of fruity and melony maybe. So this is the first test.

Elisa - It's the first small bottle. And again you don't know - because I'm not telling you - if this bottle contains the target odour or no target odour, only one, or up to five.

Katie - So this is bottle A?

Elisa - Is the target odour - the one that I just asked you to remember - in here or not?

Katie - Here goes. No, I think I know what that is. Am I allowed to say?

Elisa - You can.

Katie - I think it's DEET. I think it's an insect repellenty-type thing. I'm feeling quite confident so far.

Elisa - Let's continue with the second bottle, which is gonna be bottle C.

Katie - Oh that's nice. Smells a bit like sweets. I reckon it is in there.

Elisa - Okay halfway, two more bottles to try. Bottle E...

Katie - Hmm, bottle E I'm not sure about. I'm gonna suspend my my answer on that one.

Elisa - Okay. And then the last bottle is bottle H.

Katie - That's absolutely got it in it.

Elisa - Do you want to have a smell again of E?

Katie - Yes. On second smell, no I don't think that has got it in it.

Elisa - Alright. Here are the results. The first two bottles, as you already picked out, they were simpler and they only had one odour each. And the first bottle didn't have it, and you were correct; and the second bottle C had it. So again, the first two: both right! The following two bottles E and H had five odours each in them. So that's why it was more complicated. Again you got them both right. Maybe your colleagues have a point calling you the bloodhound of the office.

Katie - You're a smell expert so I'm going to take your word for that. Is the sense of smell capable of changing throughout our life course?

Elisa - Yes it is. Actually for women it changes every month if you're cycling. It's known that smell sensitivity is tightly controlled by hormonal fluctuations. This is work that has mostly been done in mice and not in humans. But you need to be a better smeller during the fertile period of your cycle because you need to select appropriate partners and etc, avoid predators, eat properly, especially when you're pregnant, and so on. Very, very interesting area of research that is now being investigated a little bit more, we need to look into this a little bit further. Your sense of smell can change for the worse if you have a viral infection, if you have a traumatic injury to your head; but it can also change for the better. There is this thing called smell training. It's a thing, as every sommelier or perfumer will tell you. So you can become a better smeller if you train for it. Like London cab drivers get better at navigating through London while they acquire the knowledge, which is the knowledge of all the streets in London without using a GPS, we can become better at smelling by daily training and exposing ourselves to a specific set of odours and getting better at discriminating, like similar to what we've done before, "is this odour A or odour B." But also what sommeliers especially do, it's quite difficult, you found it yourself very difficult when I made you smell the target odour: to describe it. Putting words to smell is quite challenging and it's very dependent on your culture, background etc. But you can train yourself by being able to label with words the odours more easily, and then perceive them better later on.

Katie - Okay. So I could train myself to be a better smeller. But is there any chance that I have got some sort of genetic advantage? Are some people just better at smelling than others?

Elisa - I don't know if you can define it as better or worse because it depends for which specific smell. But yes, as I was mentioning before, everybody has a unique set of olfactory receptors in the nose. It's very common for some people to lack one specific receptor genetically because they just don't have the gene. So they will not smell that odour. You could also just have more functional neurons or... we couldn't know until after a post-mortem. We shouldn't. You don't want to.

Katie - What does this mean for people for whom smells are their business? So say people who make perfumes. There's such a wide variety of smells and different people like different things, so I guess there must be lots of potential right, of different combinations?

Elisa - I think there is a terrible lot of potential. One of the main problems that they have is that when they're creating a perfume, they can't create a perfume that everybody will like. Because again as we were saying before, smell is a perception very much dependent on the cultural environment in which you were raised and you were exposed to. I read somewhere that the US military was trying to create a stink bomb that was universally repulsive, and they failed. Because there is no one smell that everybody finds repulsive. So yeah, it comes with great possibilities but also quite great challenges.

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