Zebrafish neural functioning could provide insights into workings of the human brain

Saturday 24 November 2012 12:32PM (view full episode)

Peter Neri’s research team is investigating how sensory signals are processed by the brain and then drive an animal's behaviour. His work with zebrafish gives an indication of what the fish can see. He does this my showing the fish movies of other zebrafish.  This leads to behaviour such as aggregation.  The zebrafish might be useful for addressing social dysfunction in humans.

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Robyn Williams: And from a Mexican in Australia to an Italian in Scotland, Peter Neri, who shows films to tiny fish, and they watch them and discriminate. Can you imagine showing movies to fish in a tank?

Peter Neri: Yes, I show them movies and initially I wasn't even sure that they would be able to relate to these movies, although there was some existing literature that indicated that to some extent they can recognise objects within these movies, but it was unclear to what extent they recognised those objects, how much detail they could make out, and how far they could interpret what the movie was showing.

I was expecting that they would respond to the movies somehow, but initially I didn't know, for example, whether they would respond to a movie of other zebrafish in the same way that they would respond to a movie that I generated, like a cartoon. So I started doing these experiments, and as I was performing the experiments I was surprised by how much they can actually do with such a tiny brain. They are able to discriminate details that I wasn't expecting. For example, not only can they tell that there are other zebrafish out there, and of course you can't ask them, so the only way...in order to measure, to determine whether they can discriminate them, you just track of their position, and if they go towards the movie and spend time looking at it, that gives you an indication that they are interested in it and therefore that they can make out some details that, for example, is not present in the movie on the opposite side of the tank where they don't spend much time. That's how you determine whether they can discriminate two movies.

Initially I did some very basic silly experiments, if you like. For example, on one end of the tank I would show a movie of other zebrafish, and on the other end nothing. Of course they go for the movie, but that could be for several reasons, just because there is something moving, it could be anything that moves that attracts them. So then I started showing two movies on both ends, but I manipulated the movies so that they would only differ in one specific respect. And then I determined whether they would go to one of the two movies, and that would give me an indication that that particular difference that I introduced between the two movies they were able to discriminate.

To give you an example, at one point I showed them a movie of other zebrafish, a normal movie, on the other side I flipped it upside down so that now the zebrafish in the other movie had their bellies up, so they looked like dead fish. And surprisingly they don't discriminate these two movies, they are not interested in whether the zebrafish is upside down or not. On the other hand, when I then played the other movie backwards, and this was very clear to you as a human if you look at it, it was also clear that they could do the discrimination very well. So they were able to tell whether the movie was showing a sequence of other zebrafish moving forward as would happen in the natural environment, or backwards.

Then I started asking much more detailed questions, using stimuli that were not movies of other zebrafish but they were movies that I generated in software so that I could really control every tiny aspect of the stimulus. So I would start off with a cut-out of a zebrafish in software so I could control exactly what it was doing. And first I confirmed the result that they can tell whether they are moving backwards and forwards. The reason why this is interesting, in order to be able to tell whether a fish shape is moving forward or backward you have to do two things. First you have to make out the shape of the fish and you have to decide that the head is, say, on the left and the tail is on the right. The other thing that you have to do is you have to determine in which direction the shape is moving, whether it's moving to the left or to the right.

Then you have to put them together and you have to decide whether the direction in which the fish is moving matches the direction in which the shape is facing or not. This additional operation of putting together these two bits of information to us as humans comes naturally. We don't think of it as a particularly complex operation, but we have a big brain with loads of neurons, so it would seem reasonable that we can do it. When you think about the zebrafish with such a tiny brain, it's not at all obvious that they would be able to do this additional step.

Robyn Williams: How big is it? The size of a pea, or less?

Peter Neri: It is much less, we are talking about 100,000 neurons that would do vision, and that's very, very small. To give you an example, when we analyse what we see, we do this patch by patch in what is called the primary visual cortex, which is a part of our brain that is devoted to vision, and each tiny patch that we look at, which is about the size of your thumb if you put out your arm like this, so this little bit here would take for us about 100,000 neurons, if not more, just to pick out the basic details of that.

Robyn Williams: Some people say that something like a third of our brain is given in some way to vision.

Peter Neri: Yes, I would say that is an accurate statement, particularly if you include aspects of vision such as interpreting complex attributes of objects that you see such as what are they useful for and what could I use them for, and so definitely at least one-third.

Robyn Williams: The zebrafish obviously need to recognise other zebrafish, it's in their interest to be quick and accurate because you want to stay in the shoal, and if you don't stay in the shoal you're vulnerable you get eaten.

Peter Neri: Yes, exactly, that's possibly the reason why they are so good at doing this, and that's also what makes it interesting to study this phenomenon because it is relevant to the existence of this animal. It also relates to the fact that because they like to be in a shoal, you can interpret this tendency to aggregate with other zebrafish as a sort of a social behaviour. And this is very interesting because there is the possibility that we may use the zebrafish to address dysfunctions of social behaviour in humans.

So imagine that we can identify a zebrafish, for example, that has undergone some mutation that does not like to be part of a shoal, does not like to aggregate. So you could interpret this as being a zebrafish who has some sort of disorder of social behaviour. That could be potentially an animal model that would relate in some respect to dysfunctions of social behaviour in humans...

Robyn Williams: Like autism?

Peter Neri: Like autism, for example. Obviously it sounds very far-fetched here, that we can compare shoaling in a tiny fish with social behaviour in humans, but what we can do at this stage in terms of addressing an issue like autism, if we really want to do genetics in an animal combined with physiology and quantitative studies, is limited in the sense that we have a few successful animal models that are vertebrates. The zebrafish is probably the most successful vertebrate for genetic applications in various domains, particularly in vision where I work. So it's a very attractive possibility that this additional step could be made.

Robyn Williams: What a supreme example of lateral thinking; studying fish in tanks to research autism in children. I wish him luck. Peter Neri is a Royal Society fellow at the University of Aberdeen in Scotland, and his films of zebrafish watching movies are on his website.


Peter Neri
Senior Research Fellow
Institute of Medical Sciences
University of Aberdeen
Aberdeen Scotland


Robyn Williams
David Fisher

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