WEBVTT

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This is Paul Foucher, the Conversion Science Network, talking to Bill Hansen.

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Bill organized a conference on evolution of olfaction. We happen to be on Christmas Island.

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So Bill, why did you choose olfaction as an entry point into the evolution of sensory systems?

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I think it's a cool system.

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That's the first thing in general. And I also think it's extremely important

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for many of the animals that we have chosen to work on.

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So I mainly work on insects and then they are very smelled ribbon as far as I see it.

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And this has made their olfactory sense evolve in different ways.

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And we find different themes, both peripherally and centrally,

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where they have gone in different directions.

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And as I also mentioned in my talk, that we also find these systems that exploit

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the insect olfactory system in different ways.

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And there we have like co-evolution going on, which is also very interesting

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how exquisite one system can exploit another one to dupe other organisms to

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do what they want them to do.

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Right, but now you're jumping ahead of it, right?

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Because in your talk, you made this point that actually the way we look at olfactory

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systems has sort of changed,

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that we have initially taken more of this view of, okay, let's just look at

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these receptors, let's see what they tell us about the world,

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let's see what they tell us about the stimuli that we're processing,

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and now this whole process seems to have reversed, if you want.

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So can you say something about this change? change yeah that there was also

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a little bit about the methodologies that we use so we have.

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We we started off with having a lot of we knew

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something about the olfactory system but not very much so

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what we knew was more or less that we could we could record a signal and we

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could use this signal to tell us something about what insects or other organisms

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met so therefore we We used the system as such as a detector for interesting odors.

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And we used it to identify the odors. And this way we could see,

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for instance, how have pheromone systems evolved.

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And then we could identify what one moth smells, and then the closely related

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moth smells, and the less closely related moth smells.

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And we could draw phylogenetic and evolutionary conclusions.

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Now, I think during the last decade, this has turned around a bit.

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So now we know a lot of the natural things that insects and other organisms detect.

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And now we use that to probe the olfactory system.

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So we take the reverse entry in.

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So we go in from the chemicals where we know that, for instance,

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a fruit fly likes a certain substrate. Okay, then we can use that substrate

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by using state-of-the-art chemistry.

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We can identify what these compounds are, and then we can go into the olfactory

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system, and we can look at what part of the olfactory system is tuned to detect

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these different compounds.

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So we can sort of dissect the system by odors before we dissect the odors by

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the system. Yeah, but this seems almost circular now, because this only seems

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to make sense if you really know what these odors are about.

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How do you then ground this understanding? I mean, it doesn't mean that you

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have a full understanding of the chemical composition of what we call an odor,

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and therefore you can interpret this.

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That's what's good about insects, because we know a lot of different things.

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So the first thing that people started dissecting were the pheromones.

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So in 1959, Butanant identified the first silk moth pheromone,

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what we call by using half a million females.

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Today, we can use more or less one female and one male and get to the chemical

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identity of this pheromone.

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And by then using that one, we can go into the receptor families and try to

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pull out which receptor is tuned to these different compounds.

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But also, as I said before, one of my favorites is to use deceptive systems.

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Because if you want to deceive someone and you want that to be a stable deception

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evolutionarily, you have to be really, really good because it's a constant Red Queen race.

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So if you're a flower...

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And you don't want to pay your pollinator with nectar, which is pretty expensive.

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It's sugar, constant production.

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Then you have to smell so good that the other guy, he cannot say no, he will come.

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So therefore, in many, many flowers, this has developed.

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We think of it sometimes as deception, but I find now the more I look at it,

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that if you really go into the literature, one of the biggest families,

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for instance, that we have of plants is orchids.

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And one third of the orchids are deceptive.

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So they have all invented ways

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of fooling insects to think that they are something else than they are.

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And now also in your own research here, you went through a number of stages, right?

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Because I think you were the first who highlighted this deception using,

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let's say, the smell of rotting meat.

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This was sort of the entry point in this whole issue of deception.

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And now that story has advanced quite a bit, also using very different kinds of technologies.

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So can you say something about that evolution of your own work in this area of deception?

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Well, what we actually started with was orchids. That was when we were still

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working on pheromones a lot and trying to understand the olfactory background to pheromones.

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And then we found these flowers that are really super mimicking bee pheromones

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to dupe bees to pollinate them.

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This was the collaboration with our Austrian colleagues. And that system is

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just as amazing as anything else.

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And it was a good starting point on this whole journey because these flowers,

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they do very intelligent insects, intelligent within Cytacean Mark.

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But I mean, a male bee of this species, the female will only mate with the male once.

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And each female has a unique odor. order. So when the male has mated with this

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female, he learns the order of that female and he will not go back to her because

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he knows that he will not be allowed to mate once more.

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Analogously if every flower that

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were mimicking these odors smelled the

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same the male would also learn the odor of that

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flower and would never go back so what does

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the flower do it mimics exactly the variation that

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you have between the females within these bees and in

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this way dupe the males to to go back

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and and to try complex how complex is

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this variation chemically but it's a 10 compound found

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paramount and and there are three

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or four of these that vary in proportions to

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to a certain extent and in this way they they get these individual signatures

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so that's more or less where we started but then we got into these flowers that

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smell that's what we call sexual mimicry right but then we have the the brood

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site mimicry and that's where we got more and more

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interesting because in the first one you dupe males to

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go for sex in the second one you dupe females

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to go for a place to lay their eggs and that's

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where we started on the the sardinian flowers that smell like rotten meats and

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and we first we observed the system and we saw that flesh-eating flies were

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attracted and what we found in the end was that these flowers mimic exactly

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in the order of rotting flesh to attract flies.

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But not only that, but they also mimic the increased temperature of a rotting body.

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So the flower increases more than 15 degrees above ambient temperature to actually

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attract the flies into itself.

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So the odor is a long-range attractant, and then the temperature is the short-range

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attractant that makes the fly really go into it.

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So it's a multi-sensory deception.

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Okay. But then in this case, this is all assessed at the behavioral level.

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Well, basically sitting there and looking at this long enough and seeing what

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the flies do, what the insects do.

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No, we could never have done that without having access to the olfactory system. Okay.

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First, we saw the behavior in the field, but then we used the olfactory system

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of the bee, of the fly, and so on and so forth, to really pinpoint which odors are the active ones.

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So we could never have done that without the biological system as a detector.

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So which aspects of the system did you look at at that stage?

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This was the first stage, so we only looked at the sound potentials,

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which is called an electroantenogram.

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So you look up the antenna of an insect, and then you kind of record like an

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EKG or an EEG, but here we call it an EEG.

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And on the antenna, essentially, you have the receptors that would be sensitive

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to different aspects of these molecules. Just like in your nose,

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you have thousands and millions of receptors on an insect antenna.

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An insect antenna is like an inside-out nose.

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So there are the receptors sitting on the outside, constantly exposed to the surrounding.

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So how is that work advanced now? Because sometimes also in your presentation,

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you try to show that you have now much more also electrophysiological access

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to the system, and to also more specifically pinpoint,

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let's say, the neuronal correlate, if you want, of the chemical structure of

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the specific volatile molecules that you might be interested in.

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So what has been the advance there?

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So, EAGs have been the methodology of choice for many, and it's something that anyone can do.

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So, it's today a general method in any lab working on insect semiochemicals.

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But then we have now progressed.

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So, now we go in and make recordings from single neurons on the antenna,

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and then you gain sensitivity and specificity.

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But at the same time of course you lose the wide scope of the EEG because in

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the EEG you will get peaks more or less for every compound that the antenna

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detects but the question is then,

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do you get every compound and that's probably not true but if you go for single

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neurons then you increase the sensitivity to such a degree that you really detect

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more or less everything that that single neuron detects

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but you also gain a lot of information on the system per se because you gain

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information exactly on what a specific receptor is tuned to detect it.

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But in this case, you're still stuck, if you want, at the level of single receptor neurons.

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Yes. So if the encoding of the compound, the overall compound,

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would require multiple receptor neurons, how can you access that information?

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Information, can you perform multiple recordings simultaneously on this system now?

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The first way to get at that is, of course, to make exhaustive studies of the whole antenna.

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And that's what we've actually been doing. So you record from hundreds of neurons.

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Consecutively, not at the same time, but you probe and you run and you probe and you run.

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And in this way, we have actually mapped out more or less the full system of an insect,

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like the mosquitoes for instance we have really done very

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very exhaustive screenings but what i

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guess you're getting at is the next level where we can where

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we can open the brain of the insect and we can image the first relay center

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in the brain which is the antenna lobe where you have the glomeruli and each

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glomerulus represents input from a certain receptor type and there we can and

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stimulate the antenna with the output of the gas chromatograph,

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and then we can see how different glomeruli light up in the brain of Drosophila, for instance.

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And in several species, we have such a good map of the brain,

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a constant map that is invariant, that we can map certain receptors to exactly

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the specific glomerulus that is activated.

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So we know that if this glomerulus lights up, Well, that means that the receptor

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69A is activated on the antenna.

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But now, let's take Drosophila as our example, right?

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So what's the odour space that these insects live in? How complex is this odour space?

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I think it is not as complex as ours. We have 200-300 active receptors.

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They are playing around with 50-60.

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So, I mean, it will be more reduced, but still they can encode an enormous amount of odors.

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And, I mean, if you look at all these receptors and the combinatorial coding

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that you can get between them and by getting a few or more activated and so

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on, still already by having 60,

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you can code an immense amount.

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So in terms of real, let's say, olfactory objects, how big would that space be for Drosophila?

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Dozens, hundreds, thousands?

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No, come on. We say that with our receptors, 200, 250 active ones,

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we can code an innumerable number of orders.

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And so it's more or less the same answer

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for drosophila they can more or less

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code any odor that they are exposed to yeah the base in theory right if we say

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all possible combinations of receptor neurons are being used and that's that

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space would be very large but do we know behaviorally that also that that's

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that size of of encoding space is really being used or.

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Well you're getting into very uh interesting also evolutionary questions there

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because i mean of course they have a specific repertoire of behaviorally relevant

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odors that mean something to them and that's where that's where we got an instep

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into this system by using our latest.

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Devious flower as well because we find that this flower is targeting different receptor

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populations that mean specific things to the fly to

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the fly so which which flower is that that's the

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solomon's lily in the north of israel aaron palestina

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and this one dupes drosophila to pollinate it without reward and what we found

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is that it's really hitting three types of receptors one type is saying that

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here is fermentation going on one type says that it's It's fruit going on here. This is fruit.

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And then the third one says that this is exactly your type of fruit that you

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like. So it's really like a three-step rocket.

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And it's probably not mimicking one specific thing.

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Uh substrate but it's collecting super attractive

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parts of several different stimuli

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to build up an image of

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something that the fly cannot say no to no because why am i asking why i wanted

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us to agree a little bit on on let's say the the magnitude of this of this olfactory

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space because this this should constrain a bit our questions around the the

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antenna lobe itself Because in the end,

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if we go from our receptor neurons through our antenna lobe,

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sort of in that interaction,

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the encoding of this effective olfactory space should happen, I would assume.

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So then what does the antenna lobe really contribute to this process?

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Because now you're saying, I can just look at these combinations of receptor

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responses and actually with that already I can tell you what I'm sensing out

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there in the world. So what's the antenna lobe really adding to this process?

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Well, I think the antenna lobe adds balance. So we definitely can tell what

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the receptor neurons detect by looking at activations of glomeruli.

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But as you know, with rosophila, we have the possibility to encode genetically

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our markers at any level.

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So we can encode one marker at the input part of the antenna lobe,

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and we can encode another marker at the output.

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And we can compare these two activations.

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And then we see that there are definitely things happening in the antenna lobe.

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So if, for instance, we have done a very large screening of synthetic odors that we know are.

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Positive for the fly so they will go for them in

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a bioassay and then we have other orders that

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are that are negative so they will not definitely not

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they will go away from them and what we find when

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we look at the input only we don't find any

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correlation among patterns and the balance of the orders but when we look at

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the output of the antenna lobe we found very nice clustering of of of patterns

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that are encoding attractivity and patterns that are encoding repulsion.

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So there is definitely something going on in there that is sharpening the balance

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of the message that is coming. So not the discrimination then?

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So in this case you're clustering data from the projection neurons or from the

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glomeruli, from optical imaging?

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Yes, we are doing optical imaging of both the input, so the receptor neuron

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input into the glomeruli, and then we're doing optical imaging of the projection neuron patterns.

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So in the same fly, you can do both, but using different kinds of dives.

00:18:22.385 --> 00:18:24.885
Or you can do it in different fly circles. Sure, of course. But I mean,

00:18:24.925 --> 00:18:32.645
you can clearly separate what is encoded in the input and what is going out of the system.

00:18:32.805 --> 00:18:38.345
And then we know that in between there are these large local interneurons that

00:18:38.345 --> 00:18:41.345
are shuffling messages between the glomeruli.

00:18:41.745 --> 00:18:46.005
So are you saying that then the glomeruli are just performing some transformation

00:18:46.005 --> 00:18:48.525
from an odor space into a balance space?

00:18:49.688 --> 00:18:53.328
In some way, that's what we're seeing right now, that there seems to be something

00:18:53.328 --> 00:18:57.008
going on that gives meaning to these orders.

00:18:58.788 --> 00:19:03.988
This is really very interesting, but also a bit, in some sense, counterintuitive, no?

00:19:04.068 --> 00:19:08.128
Because we have this projection that's going to the mushroom bodies that many

00:19:08.128 --> 00:19:10.868
people have talked about, that have been, let's say, really very much involved

00:19:10.868 --> 00:19:14.828
in associative learning and especially also valence-driven learning.

00:19:14.988 --> 00:19:18.868
So how should we now compare this interpretation to this more standard view

00:19:18.868 --> 00:19:21.408
on this happening at the level of the mushroom bodies?

00:19:21.688 --> 00:19:27.808
No, but I think there is an initial sorting, and then this gets refined as they move up the system.

00:19:28.048 --> 00:19:33.068
And then you have the two pathways. If you know the insect system,

00:19:33.168 --> 00:19:36.748
you know that there is one pathway that goes from the antenna lobe to the mushroom

00:19:36.748 --> 00:19:39.748
body, and then it goes out into the lateral protocephalogram.

00:19:40.308 --> 00:19:44.828
But then we have one that totally bypasses the mushroom bodies and goes direct

00:19:44.828 --> 00:19:50.128
to the lateral horn or the lateral crotocerebral.

00:19:50.468 --> 00:19:55.888
And there we think that these two pathways are mediating different things.

00:19:56.028 --> 00:20:05.428
One is taking the road over the conscious center of the insect brain and then

00:20:05.428 --> 00:20:07.808
going out to maybe the executive center.

00:20:07.988 --> 00:20:10.968
But one path is going directly to the executive.

00:20:11.548 --> 00:20:14.608
And i think our feeling is that maybe

00:20:14.608 --> 00:20:17.788
this maybe this is extremely important especially for

00:20:17.788 --> 00:20:20.608
this reflexive pathway so that you need a

00:20:20.608 --> 00:20:23.828
sorting already here to tell the reflexive pathway

00:20:23.828 --> 00:20:27.488
what is going on yeah it would still be strange i mean i'm a bit confused now

00:20:27.488 --> 00:20:32.548
because in some sense it would mean that if if my output from my from my antenna

00:20:32.548 --> 00:20:37.728
load processing is just if you want good or bad um the balance of of the stimuli

00:20:37.728 --> 00:20:40.868
i'm dealing with and i lose my discrimination determination abilities i cannot

00:20:40.868 --> 00:20:42.928
say anymore whether it was an apple or an orange.

00:20:43.588 --> 00:20:46.448
You would expect that also for let's say your

00:20:46.448 --> 00:20:49.668
behavior this might be rather unspecific yeah but

00:20:49.668 --> 00:20:54.908
i don't i that's going too far i think because because it yeah it seems like

00:20:54.908 --> 00:21:00.908
you have clusters so so within each cluster of of there might be 15 glomeruli

00:21:00.908 --> 00:21:05.068
so one saying apple one saying orange one saying pineapple one saying banana

00:21:05.068 --> 00:21:08.008
and and i mean but but it seems like what

00:21:08.048 --> 00:21:10.788
we're finding is that these that say something good,

00:21:11.807 --> 00:21:16.087
and sort of take part in the combinatorial coding of something that is good.

00:21:16.227 --> 00:21:21.587
They seem to be in some way clustered and have become clustered during evolution.

00:21:21.907 --> 00:21:26.707
And the glomeruli, maybe also 10 or 15, that are saying that something is bad,

00:21:26.807 --> 00:21:29.007
they have also become clustered in another way.

00:21:29.187 --> 00:21:35.387
And this makes it possible for us by principal component analysis to say, to predict.

00:21:36.307 --> 00:21:41.287
Was this pattern, was this activation pattern in the antenna lobe,

00:21:41.807 --> 00:21:44.767
for a an attractive odor or was

00:21:44.767 --> 00:21:47.467
it for a repulsive all right so you're saying

00:21:47.467 --> 00:21:50.467
it's like a multidimensional code it's something like on the

00:21:50.467 --> 00:21:55.727
one hand it will tell you what it is like this is a banana and it's good yeah

00:21:55.727 --> 00:22:00.207
or this is some acid and it's bad so it will tell you both yeah all right so

00:22:00.207 --> 00:22:04.407
but why at the level of the antenna also from an evolutionary and behavioral

00:22:04.407 --> 00:22:10.327
perspective it seems counterintuitive that already at this early processing stage we start to label.

00:22:10.987 --> 00:22:13.687
Stimuli with respect to valence or not do you

00:22:13.687 --> 00:22:16.687
find this intuitive i i don't find

00:22:16.687 --> 00:22:20.587
it so counterintuitive because if we we

00:22:20.587 --> 00:22:26.307
think that the system has evolved by by glomeruli splitting and forming new

00:22:26.307 --> 00:22:31.067
ones you know you have the evolution of a receptor by a mutation of a previous

00:22:31.067 --> 00:22:37.287
existing one and this adds a new glomerulus in in the antenna so this means that

00:22:37.327 --> 00:22:40.447
maybe you had one detecting something,

00:22:40.647 --> 00:22:45.767
a good fruit of some kind, but then you got a refinement that was evolutionarily

00:22:45.767 --> 00:22:50.187
advantageous, that they could detect another kind of fruit,

00:22:50.767 --> 00:22:55.007
that might be good to separate from the ones they knew already before.

00:22:55.407 --> 00:22:59.867
So then you got the glomerulus added, and these glomerulus will very likely

00:22:59.867 --> 00:23:03.887
be added close to the one that it was split off from.

00:23:04.487 --> 00:23:07.647
And in this way, I see that these clusters have formed.

00:23:07.927 --> 00:23:14.487
I don't see that they really, they might not really form a functionally important cluster.

00:23:17.452 --> 00:23:22.972
Functionally important character, but I find that it's evolutionarily interesting,

00:23:23.572 --> 00:23:31.592
because these clusters have been built maybe from some proto-glomerulus that they all stem from.

00:23:32.012 --> 00:23:34.052
So there has been a few bad ones,

00:23:34.152 --> 00:23:37.212
a few good ones, but then these have evolved and become more and more,

00:23:38.012 --> 00:23:42.952
If the way it's derived now sounds a bit like I can keep on adding glomeruli

00:23:42.952 --> 00:23:48.152
until my skull is filled up or my exoskeleton explodes because I have no more

00:23:48.152 --> 00:23:51.392
space if I look at the mouse the mouse has 1200,

00:23:52.692 --> 00:23:58.572
but they are much much smaller so you can I think you can keep on adding glomeruli

00:23:58.572 --> 00:24:03.512
but I think there is also an end to when you need more,

00:24:04.392 --> 00:24:09.392
that was the whole issue of the effective stimulus space but then in Drosophila

00:24:09.392 --> 00:24:14.892
to what extent is this really genetically predefined or to what extent and isn't

00:24:14.892 --> 00:24:17.772
really open to the stimuli the animal is exposed to.

00:24:19.492 --> 00:24:22.992
What is predefined? The number of glomeruli that they will express.

00:24:24.172 --> 00:24:29.852
I think it is definitely predefined in the drosophila that we work on today.

00:24:30.132 --> 00:24:36.832
I mean, we can go from individual to individual to individual, and it will be constant.

00:24:37.312 --> 00:24:41.672
And we know that glomerulus D, it's always there.

00:24:41.792 --> 00:24:44.612
We can find it. right so so that

00:24:44.612 --> 00:24:48.072
that one is is pretty fine but then i'm also sure that

00:24:48.072 --> 00:24:51.352
there can be during evolution a mutation that is

00:24:51.352 --> 00:24:54.412
advantageous enough to be become fixed in

00:24:54.412 --> 00:24:57.892
the population that creates a new a new receptor but

00:24:57.892 --> 00:25:01.332
then we also know that receptors can pseudogenize and they

00:25:01.332 --> 00:25:04.052
become inactive so so i'm i mean the

00:25:04.052 --> 00:25:07.412
over evolutionary over evolutionary time the

00:25:07.412 --> 00:25:10.592
the system can change it can go backwards it

00:25:10.592 --> 00:25:14.132
can go forwards it can go left or right so

00:25:14.132 --> 00:25:17.152
so i'm sure i'm sure that things are happening there but

00:25:17.152 --> 00:25:21.132
but they take a little too long for us to observe them right what we can do

00:25:21.132 --> 00:25:26.332
is to go and compare species and that's what we're doing so we can for instance

00:25:26.332 --> 00:25:33.532
look at all the 12 species of the melanogaster group and and see okay did we

00:25:33.532 --> 00:25:37.012
have for instance looked at what does diet change mean?

00:25:37.292 --> 00:25:42.492
So we have one species that have started eating only one single fruit out on the Seychelles.

00:25:43.372 --> 00:25:46.732
And this fruit smells very, very strongly of a pineapple odor,

00:25:46.912 --> 00:25:49.512
ethyl hexanoate, and of acids.

00:25:49.912 --> 00:25:53.632
And the acids make the other species more or less die when they eat it.

00:25:53.892 --> 00:25:59.532
And here we find a very, very strong effect on the olfactory system of the fly.

00:25:59.752 --> 00:26:10.832
So this fly has more or less sacrificed three or four other cells that are active in detecting the.

00:26:12.933 --> 00:26:16.193
The sort of normal drosophila melanogaster odors and

00:26:16.193 --> 00:26:19.713
instead into those and see like it has put cells that only

00:26:19.713 --> 00:26:23.933
detect this new type of fruit so so

00:26:23.933 --> 00:26:27.113
it has zoomed in it has totally zoomed

00:26:27.113 --> 00:26:30.313
in its its peripheral system towards this

00:26:30.313 --> 00:26:33.573
fruit and at the same time it has increased the

00:26:33.573 --> 00:26:37.053
center of the brain the glomeruli that takes care

00:26:37.053 --> 00:26:41.013
of this input by 200 percent so so

00:26:41.013 --> 00:26:43.813
it's it's really the first example we know this from

00:26:43.813 --> 00:26:46.893
sex detection in moths that the

00:26:46.893 --> 00:26:49.833
male has increased the number of detecting units enormously

00:26:49.833 --> 00:26:55.353
and at the same time expanded his brain area taking care of female input enormously

00:26:55.353 --> 00:26:59.433
but this was the first time we see such a thing happening with when it comes

00:26:59.433 --> 00:27:05.113
to food and diet but then is it is it really the case that for these insects

00:27:05.113 --> 00:27:07.293
just allocating more real

00:27:07.373 --> 00:27:11.873
estate to the processing of the signal increases their discrimination ability?

00:27:12.733 --> 00:27:17.513
Is that all it takes? I would say that it increases their detection ability.

00:27:17.773 --> 00:27:22.093
Because these flies, they're a bit weak, and they have one competitor.

00:27:22.353 --> 00:27:26.153
And if they are not there first, they will be out-competed by the other guy.

00:27:26.433 --> 00:27:31.973
So they're very dependent on detecting the fruit at an early stage of ripeness.

00:27:32.693 --> 00:27:35.653
At least that what i told you of the of this

00:27:35.653 --> 00:27:38.513
amplification by numbers is not the only thing because

00:27:38.513 --> 00:27:41.353
they have also boosted the sensitivity of each neuron

00:27:41.353 --> 00:27:50.333
by about a thousand times so so they have they have maybe 200 more neurons and

00:27:50.333 --> 00:27:54.713
then each neuron is a thousand times more sensitive so we get down to a detection

00:27:54.713 --> 00:28:00.093
limit that very very clearly competes with moth pheromone detection,

00:28:00.213 --> 00:28:02.493
which is among the most sensitive we know before.

00:28:02.873 --> 00:28:08.253
So we're down to picogram, nanogram of compound being detected.

00:28:08.653 --> 00:28:15.413
In terms of these detection thresholds, what's the sensitivity for drosophila

00:28:15.413 --> 00:28:18.133
at the periphery for these kinds of stimuli?

00:28:18.433 --> 00:28:23.933
And is that sensitivity also boosted by the processing that happens in these

00:28:23.933 --> 00:28:26.673
glomeruli in some way? Or you don't know?

00:28:29.191 --> 00:28:34.331
What we know is that we go down to levels of moth pheromone communication,

00:28:34.671 --> 00:28:40.211
where we can be playing with 10 molecules, which is really homeopathic concentrations.

00:28:41.631 --> 00:28:48.131
Then what we have observed in our investigations before is that we sometimes

00:28:48.131 --> 00:28:52.971
see a boost in amplification at the next level.

00:28:53.811 --> 00:28:59.471
And this boost we still cannot explain. And we see sometimes a similar thing in Drosophila.

00:28:59.611 --> 00:29:05.931
So there is something going on after the receptor neuron has detected with its sensitivity.

00:29:06.431 --> 00:29:12.071
And then to the output levels of the antenna load, we see an augmentation of

00:29:12.071 --> 00:29:14.751
sensitivity that we still cannot really explain.

00:29:15.071 --> 00:29:18.851
Okay. So if we talk about things that cannot be explained, so would you claim

00:29:18.851 --> 00:29:21.711
that to a large extent you understand the system now?

00:29:21.791 --> 00:29:24.131
Could you really make that claim?

00:29:24.391 --> 00:29:28.151
Oh, no. Okay. Okay, so where are we with respect to our understanding of this system?

00:29:29.951 --> 00:29:34.531
Despite the very big investigations, both from our lab,

00:29:34.671 --> 00:29:38.731
but even more from other labs that have come out lately on these local interneurons,

00:29:38.871 --> 00:29:45.551
we still don't understand what they do that shuffle the message between glomeruli. Secondly...

00:29:46.845 --> 00:29:50.965
We lack one very basic thing, and that is how things are hooked up.

00:29:52.265 --> 00:29:56.285
And that's why we're now entering into very, very detailed electron microscopic

00:29:56.285 --> 00:29:59.505
investigations of single neurons,

00:29:59.665 --> 00:30:05.945
of single glomeruli, and trying to understand how are really receptor neurons

00:30:05.945 --> 00:30:07.465
hooked up to local neurons,

00:30:07.645 --> 00:30:09.545
how are hooked up to projection neurons.

00:30:09.745 --> 00:30:13.065
Are there things feeding back in the system?

00:30:14.645 --> 00:30:21.065
Why do you need to know this? Well, you can never understand the system unless you know how it's wired.

00:30:22.165 --> 00:30:27.225
We don't even know the basics. No one has ever taken the trouble of looking

00:30:27.225 --> 00:30:28.625
at the very, very basics.

00:30:28.845 --> 00:30:34.385
There's one study of cockroaches 10 years, 15 years ago, where Dagmar Malun

00:30:34.385 --> 00:30:39.965
in Jürgen Birch's lab actually took the trouble of looking at some of the connectivity

00:30:39.965 --> 00:30:41.945
of the antenna load. Okay.

00:30:42.405 --> 00:30:47.625
But, I mean, you have neurons that are coming in, and you don't even know what they hook up to.

00:30:47.985 --> 00:30:52.805
We hypothesize that they might hook up to this neuron or they might hook up

00:30:52.805 --> 00:30:55.525
to that neuron, but we still don't know.

00:30:55.765 --> 00:30:59.825
Yeah, but look, on the other hand, you do have a lot of electrophysiology of this system.

00:30:59.885 --> 00:31:03.285
You know what these projection neurons that are reading out the glomeruli,

00:31:03.465 --> 00:31:05.665
how they are responding to different kinds of stimuli.

00:31:05.965 --> 00:31:09.785
Yeah, but why do they respond like that? No, but you also know the dynamics of the glomeruli.

00:31:09.985 --> 00:31:15.105
So that means apparently something is missing from the pure physiological perspective.

00:31:15.105 --> 00:31:16.265
So what is missing there?

00:31:16.305 --> 00:31:18.965
And what's the ambiguity exactly you're trying to resolve now?

00:31:19.105 --> 00:31:20.845
But there are still different schools.

00:31:21.245 --> 00:31:26.585
There is the Nobel Prize winner, Richard Axel School, who say that nothing is happening.

00:31:27.445 --> 00:31:31.865
Things are coming in and things are going out. And it's the same.

00:31:32.963 --> 00:31:38.183
And then there is the more Gilles Laurent school that says that things are coming

00:31:38.183 --> 00:31:41.883
in, then they are modified, and then they go out.

00:31:42.403 --> 00:31:46.563
And here, in this case, I more agree with the Laurent school.

00:31:46.643 --> 00:31:48.823
I think more and more are doing that.

00:31:49.343 --> 00:31:53.903
Of course, things are happening in the antenna lobe. It's not just a relay station.

00:31:53.903 --> 00:31:59.163
Why would we have hundreds and sometimes thousands of local neurons shuffling the message,

00:32:00.043 --> 00:32:02.903
if you wouldn't need a modification in there

00:32:02.903 --> 00:32:05.843
well you could have as i say a simple interpretation i will

00:32:05.843 --> 00:32:09.343
need some gain control because concentrations can vary and

00:32:09.343 --> 00:32:13.943
i should sort of regulate now the amplitude of my responses and that's it but

00:32:13.943 --> 00:32:19.083
that's nothing to do with encoding this olfactory space itself of course you

00:32:19.083 --> 00:32:23.263
could have but we don't see that that's not what we observe as i told you we

00:32:23.263 --> 00:32:25.903
We see sharpening of images.

00:32:26.263 --> 00:32:32.923
We see what we think is contrast enhancement, where one odor can more or less

00:32:32.923 --> 00:32:34.863
turn off all the other glomeruli.

00:32:35.043 --> 00:32:40.983
It increases the response in one glomerulus enormously, and it depresses the

00:32:40.983 --> 00:32:43.943
response in all other glomeruli in the whole antenna lobe.

00:32:44.143 --> 00:32:49.743
Okay. So there are definitely things similar to the visual system going on in there.

00:32:49.943 --> 00:32:56.303
All right. So in terms of how we encode this olfactory world.

00:32:58.035 --> 00:33:02.215
Are you also there looking more at, let's say, the Laurent interpretation,

00:33:02.775 --> 00:33:05.975
like we have some kind of possible temporal coding coming out of the system?

00:33:06.455 --> 00:33:11.495
Or do you think you see a more spatial kind of coding or rate kind of coding?

00:33:11.615 --> 00:33:12.915
So where are you going there?

00:33:13.435 --> 00:33:17.235
Because in the end, of course, for the rest of the brain, what matters is not

00:33:17.235 --> 00:33:20.895
what the glomeruli do, it's what the projection errors are telling the rest of the system, right?

00:33:21.975 --> 00:33:25.015
I think we have to look in both ways all the time.

00:33:25.015 --> 00:33:32.615
I definitely think there is a spatial code of some kind, but what that really

00:33:32.615 --> 00:33:37.015
means in the readout, I mean, what really means something is which projection

00:33:37.015 --> 00:33:38.195
neuron will get activated.

00:33:38.195 --> 00:33:41.775
It and and i mean is this

00:33:41.775 --> 00:33:45.535
is the spatial code just a product of

00:33:45.535 --> 00:33:48.635
of that we we have glomeruli in there and it's parcel

00:33:48.635 --> 00:33:51.495
in this way so that what what we

00:33:51.495 --> 00:33:57.295
what we choose to see as as a spatial map is is a product of of the connectivity

00:33:57.295 --> 00:34:01.435
of the antenna lobe i i don't think that's so important i think the main thing

00:34:01.435 --> 00:34:06.755
is that certain receptor neurons come into one location and the message of those

00:34:06.755 --> 00:34:10.975
receptor neurons are mainly picked up by projection neurons at the same location.

00:34:12.095 --> 00:34:15.095
So in that way, you could say that you have some kind of spatial map.

00:34:15.375 --> 00:34:20.375
But then at the same time, I think it's really important to not forget the temporal

00:34:20.375 --> 00:34:24.175
aspects, but you also have to choose the way that you look at it.

00:34:24.675 --> 00:34:28.335
I get very confused by some of the studies that have been done,

00:34:28.435 --> 00:34:30.855
and I still struggle to understand them really.

00:34:31.855 --> 00:34:34.655
For what reason? I mean, what's the confusing bit?

00:34:36.635 --> 00:34:37.255
Took,

00:34:39.049 --> 00:34:47.649
I mean, you get very, very intricate analysis going on of the oscillations going

00:34:47.649 --> 00:34:52.109
on, for instance, in the antenna lobe and the mushroom body and so on.

00:34:52.309 --> 00:34:58.469
And I'm still not, I still haven't got my brain all ready with that.

00:34:58.989 --> 00:35:02.349
Right. It also has been fairly, it's not that this is all clear cut,

00:35:02.469 --> 00:35:03.589
right? There's still quite some debate.

00:35:03.909 --> 00:35:07.329
Oh, there's a lot of debate. This is the right way to look at it, yeah. Yeah.

00:35:07.769 --> 00:35:11.529
But I also have this feeling that we have more to learn about,

00:35:11.689 --> 00:35:13.289
for instance, coincidence detection.

00:35:14.569 --> 00:35:18.689
I think that is one way that you could augment the sensitivity of the system

00:35:18.689 --> 00:35:22.849
in the way that we don't understand right now, so that we see the higher sensitivity

00:35:22.849 --> 00:35:29.309
at the second level that we could explain by theory from just a mere convergence.

00:35:29.309 --> 00:35:35.189
And this higher increase could be explained by, for instance,

00:35:35.269 --> 00:35:38.549
cells going into synchrony on

00:35:38.549 --> 00:35:42.389
the antenna, and then this synchrony being detected in the antenna lobe.

00:35:42.469 --> 00:35:46.229
And that's exactly what we're trying to get at now by doing multiple recordings

00:35:46.229 --> 00:35:50.309
from neurons on the antenna. So have you seen this kind of synchrony?

00:35:50.669 --> 00:35:54.749
The analysis, we did it a few months back.

00:35:54.749 --> 00:36:00.569
But the analysis to get at, to get really, to get, okay, here the stimulus reaches

00:36:00.569 --> 00:36:05.749
both of these neurons exactly at this millisecond, and then go into the analysis

00:36:05.749 --> 00:36:09.569
and say that, okay, after 10 milliseconds, they start spiking together.

00:36:09.909 --> 00:36:15.889
Right. That takes some time. Okay. So now, we'll talk about the evolution here,

00:36:15.969 --> 00:36:17.069
right, certainly in this meeting.

00:36:17.809 --> 00:36:21.329
And it was sort of interesting, maybe also ironic, that you said,

00:36:21.409 --> 00:36:25.329
well, olfaction is a bit like a visual system. But from an evolutionary perspective,

00:36:25.589 --> 00:36:28.749
you could also make the argument that actually the visual system is like the olfactory system.

00:36:29.449 --> 00:36:32.529
And so where do you stand on that issue?

00:36:32.609 --> 00:36:38.209
Do you see really that the olfactory system is like a proto-sensory system?

00:36:39.193 --> 00:36:43.013
Whose principles have been generalized towards other modalities,

00:36:43.093 --> 00:36:44.473
or what's your take on that?

00:36:46.953 --> 00:36:51.213
I think all these sensory systems are created from cilia.

00:36:51.933 --> 00:36:58.273
And cilia were there from the beginning. We have cilia in different forms on all organisms.

00:36:58.693 --> 00:37:01.833
And as Heather Eisen was saying in her talk here at the conference,

00:37:01.833 --> 00:37:10.453
for instance, probably chemoreception and mechanoreception were the two first sensory systems.

00:37:11.213 --> 00:37:19.153
And if we then compare, probably the cilia of the visual system might have occurred

00:37:19.153 --> 00:37:22.673
from the mechanosensories and cilia in some way.

00:37:22.773 --> 00:37:25.713
And you have got the rhodopsin integrated and so on.

00:37:26.533 --> 00:37:31.833
So I think it's very hard to talk about the proto-sense of some way.

00:37:33.213 --> 00:37:38.233
I find the old theory... That is interesting because you're sidestepping the

00:37:38.233 --> 00:37:41.573
issue a bit by focusing so much at the sensory periphery, right?

00:37:41.633 --> 00:37:46.533
You could still argue that the processing that has been performed,

00:37:46.733 --> 00:37:50.973
is being performed by the antenna lobe, combined with their projection neurons,

00:37:51.253 --> 00:37:55.833
and maybe a little bit downstream from that, that provides, let's say,

00:37:55.873 --> 00:37:59.433
the proto-processing principles of any sensory modality,

00:38:00.613 --> 00:38:04.293
irrespective of how the periphery gets you the specific signals.

00:38:04.633 --> 00:38:06.973
Would you buy that? Also that you would not buy necessarily.

00:38:08.793 --> 00:38:13.073
I mean, you can compare it. If you look at audition hearing,

00:38:13.333 --> 00:38:18.533
then you have this, that you have certain frequencies being taken care of in

00:38:18.533 --> 00:38:21.453
certain barrels in our auditory cortex and so on.

00:38:21.453 --> 00:38:28.233
So I think that this parcellation definitely occurs in different sensory systems. On the other hand,

00:38:29.588 --> 00:38:33.528
The glomerulus formation we see all over the place.

00:38:35.468 --> 00:38:41.668
We see some organisms that have an agglomerular input from receptor neurons,

00:38:41.768 --> 00:38:43.308
but I see them as the exception.

00:38:43.548 --> 00:38:47.808
I don't agree with some of what we heard earlier here at the conference,

00:38:47.948 --> 00:38:49.268
that there are many, many.

00:38:49.448 --> 00:38:51.808
I think there are a few where we don't see this.

00:38:53.088 --> 00:38:57.248
But take an antenna and move it to the place of a leg of a fly,

00:38:57.248 --> 00:39:02.888
and glomeruli will be formed where the nerves hit the nervous system.

00:39:03.068 --> 00:39:08.468
So I mean, olfactory receptor neurons have the capability of forming glomeruli

00:39:08.468 --> 00:39:11.848
where they hit the olfactory system in more or less any organism.

00:39:12.148 --> 00:39:17.108
So this seems to be a general principle that has evolved probably independently

00:39:17.108 --> 00:39:22.588
in several different lineages during evolutionary time.

00:39:22.588 --> 00:39:28.308
So I think that is a very basic way of organizing chemo detection.

00:39:29.228 --> 00:39:34.528
But then if you look at how visual, then you don't see this kind of architecture.

00:39:35.788 --> 00:39:40.108
Well, but still you would have some patterns of convergence and divergence that

00:39:40.108 --> 00:39:45.568
are especially convergence initially that are regulated in some form.

00:39:45.568 --> 00:39:52.108
So you might speculate to say, well, the formation of the glomerulus is like

00:39:52.108 --> 00:39:53.648
your proto-receptive field.

00:39:54.168 --> 00:39:58.068
And other sensory modalities that's thrown in, let's say, a thalamus,

00:39:58.068 --> 00:40:03.748
an intermediate processing stage, just developed a more complicated form of a glomerulus.

00:40:03.988 --> 00:40:09.248
But now it really became a mechanism to define more complex receptive fields.

00:40:09.388 --> 00:40:13.008
I mean, I'm just sucking this out of my thumb right now, but you could tell

00:40:13.008 --> 00:40:15.228
a story along these lines that you could try to defend.

00:40:15.668 --> 00:40:20.508
But that's not necessarily one you would buy right now. You would really see

00:40:20.508 --> 00:40:23.128
it as separate principles for separate modalities.

00:40:24.961 --> 00:40:30.201
Yes, basically. But at the same time, I agree that you can definitely have receptive

00:40:30.201 --> 00:40:32.761
fields and that it gets organized, of course.

00:40:33.121 --> 00:40:36.121
Organization is needed for sensory detection.

00:40:36.441 --> 00:40:40.821
Right. But I don't see direct parallels when I look at the olfactory system

00:40:40.821 --> 00:40:42.441
and the visual system, for instance.

00:40:43.581 --> 00:40:47.321
So I think more and more science is needed.

00:40:47.461 --> 00:40:53.881
But before we can say that, there has been a lot of evolution going on since they were born.

00:40:53.881 --> 00:40:57.001
Yeah that that's what you guys tell me so now

00:40:57.001 --> 00:41:00.501
um so another thing you're

00:41:00.501 --> 00:41:04.701
doing here on the island is to look at specific species of crabs or specific

00:41:04.701 --> 00:41:09.121
particular one the rubber crab right so so why is that really how is this helping

00:41:09.121 --> 00:41:14.301
us to understand your factory system well here we are really interested in understanding

00:41:14.301 --> 00:41:17.941
how does the sensory system adapt during evolutionary time

00:41:18.181 --> 00:41:24.341
to go from detection in water to detection in air and this has happened during

00:41:24.341 --> 00:41:29.961
the last five million years it's a pretty fast process and we know also interesting

00:41:29.961 --> 00:41:31.641
new facts about different kinds of

00:41:31.641 --> 00:41:36.601
receptors detecting different kinds of stimuli we know that this the old.

00:41:38.033 --> 00:41:43.053
Evolutionarily, probably old ionopropyl receptors are very active in detecting

00:41:43.053 --> 00:41:44.973
waterborne compounds and so on.

00:41:45.533 --> 00:41:50.733
So what we're trying to look at is basically all the way from the antenna into

00:41:50.733 --> 00:41:52.753
the brain, what has happened to these guys.

00:41:53.113 --> 00:41:57.473
And it's not only in this species, but then we're comparing to other species.

00:41:57.733 --> 00:42:02.213
And what we find really interesting is that different species of crustaceans

00:42:02.213 --> 00:42:05.333
have taken totally different evolutionary pathways.

00:42:05.333 --> 00:42:11.693
Pathways so out of the five lineages that went down to land we have chosen mainly

00:42:11.693 --> 00:42:18.773
two to look at and that's the the hermit crabs and the isopods the woodlice and they have taken,

00:42:19.553 --> 00:42:22.473
diametrically different pathways so the the

00:42:22.473 --> 00:42:27.913
hermit crabs they have expanded the brain area that take care of olfactory input

00:42:27.913 --> 00:42:35.573
to occupy almost 50 percent of their brain while isopods have totally decreased

00:42:35.573 --> 00:42:41.133
almost to zero the part of their brain that takes care of olfactory input.

00:42:41.493 --> 00:42:48.593
So I find this very interesting. Why do two different types of the same type

00:42:48.593 --> 00:42:52.533
of animal, crustacean basically, when they go on to land.

00:42:53.513 --> 00:42:57.373
Go in so diametrically different evolutionary directions?

00:42:57.813 --> 00:43:01.833
And that's what we're trying to understand. To understand it, we do,

00:43:01.833 --> 00:43:06.653
do we have we are studying the antenna we're studying all the receptors set

00:43:06.653 --> 00:43:11.513
up so far we have only found gustatory receptors and ionotropic receptors we

00:43:11.513 --> 00:43:18.673
cannot find our type of olfactory or the insect type right and at the same time

00:43:18.673 --> 00:43:21.073
we're doing the brain anatomy we're looking at

00:43:21.313 --> 00:43:26.413
how it's built how things project how the different centers are constructed

00:43:26.413 --> 00:43:32.413
comparing comparing between isopods and crustaceans and the hermits and so on.

00:43:33.766 --> 00:43:37.906
We were in the middle of that project, but evolutionarily I find it extremely

00:43:37.906 --> 00:43:43.086
interesting because we have sort of an experiment that has been going on during

00:43:43.086 --> 00:43:44.326
the last five million years.

00:43:44.586 --> 00:43:49.546
Right. But now it seems a bit counterintuitive, right? Because aren't you sort

00:43:49.546 --> 00:43:52.086
of swimming against the current now?

00:43:52.266 --> 00:43:56.566
Because, you know, we have preparations like Drosophila, like the mouse,

00:43:56.746 --> 00:44:02.266
which are in some sense becoming now the standard preparation because we know so much about them.

00:44:02.266 --> 00:44:07.326
And what we have is molecular access to them that they can become highly controlled

00:44:07.326 --> 00:44:08.406
experimental preparations.

00:44:08.806 --> 00:44:14.286
And now you come and you find some really very odd crab species to start to

00:44:14.286 --> 00:44:16.246
look at, about which we know very little.

00:44:16.486 --> 00:44:18.986
So isn't it a high-risk operation?

00:44:19.946 --> 00:44:23.666
Of course, but at the same time, I think it's highly dangerous to get stuck

00:44:23.666 --> 00:44:25.186
only in the model species.

00:44:25.726 --> 00:44:30.966
So we should use the model species to the utmost, and I really like working

00:44:30.966 --> 00:44:34.966
on Drosophila, But at the same time, of course, we need a comparison with other systems.

00:44:35.886 --> 00:44:40.886
Otherwise, we get extremely narrow in our view of the world.

00:44:41.186 --> 00:44:46.026
And we get totally Drosophila-centric or Musa-centric or whatever you would say.

00:44:46.526 --> 00:44:50.946
And I mean, we need comparison. And to understand evolution specifically,

00:44:51.266 --> 00:44:54.646
you can never understand evolution only by looking at Drosophila melanogaster,

00:44:54.706 --> 00:45:02.046
an animal that has been totally associated with humans during the last 15,000 or 25,000 years.

00:45:02.526 --> 00:45:07.546
So it's really, really needy that we also keep our eyes open,

00:45:07.626 --> 00:45:09.246
and that's what I really like to do.

00:45:09.286 --> 00:45:15.646
I like to use the model system, but I also really like to go outside of that

00:45:15.646 --> 00:45:19.586
and to try to understand what has really gone on in nature.

00:45:20.226 --> 00:45:24.306
Right. So then how many years will it take for us to understand this crab now?

00:45:25.466 --> 00:45:28.346
Oh they you know when you start that

00:45:28.346 --> 00:45:31.186
on a new system like this one first you have

00:45:31.186 --> 00:45:34.026
to nail down the the ecology of the

00:45:34.026 --> 00:45:37.086
species to try to understand what they are doing and what

00:45:37.086 --> 00:45:41.286
you should basically do is just to sit down in your ass for one year and watch

00:45:41.286 --> 00:45:46.406
the crab but we don't have time to do that most of us so are you good in this

00:45:46.406 --> 00:45:52.126
we i now have one postdoc on the island and she's doing massive marking of the

00:45:52.126 --> 00:45:55.946
crabs and we're really trying to get the impression of what's going on.

00:45:56.146 --> 00:46:01.306
And we're marking them with GPS loggers and so on to try to understand their

00:46:01.306 --> 00:46:04.586
movements and basically how they interact.

00:46:04.766 --> 00:46:07.146
But all of this is supposed to form the base for...