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When Christopher Columbus made landfall in San Salvador in 1492, he was convinced he had reached Asian shores. If he, like Amerigo Vespucci some years later, had attempted to draw a map of the coastal line, he would have noticed his mistake. “Maps are powerful tools that can help us to make sense of the world while we draw them,” says Martha Nari Havenith, who is one of ESI’s group leaders. In a recent publication she and her team demonstrate that many researchers working with mice stick to a brain map that – figuratively speaking – makes them believe they are in Asia, while truly they stepped ground in the Americas.

Just like geographers have created maps detailing every corner of the earth, neuroscientists are creating maps that chart different properties of the brain. This way they are trying to work out the boundaries between brain areas that fulfill different tasks. However, compared to how much we know about earth, we are only just starting to understand the brain, which is why modern day neuroscientists every now and then may be facing problems similar to those the explorers of the new world had: Their maps sometimes reflect what is commonly accepted to be, rather than what really is. Martha Nari Havenith and colleagues found this to be particularly true for certain areas of mouse and rat brains.

Different findings

“I would never have noticed, if my PhD student Sabrina hadn’t been so diligent in comparing her findings to the literature,” remembers Martha Nari Havenith. Sabrina van Heukelum had investigated the function of a brain area called anterior cingulate cortex, or short ACC. ACC plays an important role in making sure we behave appropriately to a situation at hand, by processing emotional information and keeping impulsive behavior in check. In experiments with mice, Sabrina van Heukelum was digging into the mechanism through which ACC controls aggressive behavior. What she observed was that based on anatomical characteristics ACC could be divided in two spatially separate sub-areas: Comparing aggressive mice with less aggressive mice, one of the two areas was increased in volume, while the other was decreased.

A clear-cut finding and one that fits what is known from humans and monkeys. There, based on detailed mapping of neuronal function, a big part of ACC has been defined as a separate area, called midcingulate cortex, or MCC. While ACC is an expert for processing emotions, MCC has a stronger affinity for solving cognitive tasks. For mice however a similar division of labor in cingulate cortex is not well established, explains Martha Nari Havenith: “Initially we thought the research looking at cingulate cortex in mice is still in its infancy and that would explain why the effect we found isn’t as clear for rodents.” But then Sabrina van Heukelum started to dig deeper. She compared her own data with what was reported in the literature and realized: Many studies would probably have been able to describe the same effect she had found, if they had used the same brain map.

Different maps

The maps that are most commonly used in order to navigate through brains of rats and mice do not partition cingulate cortex on the grounds of a functional division into ACC and MCC as it is common for most species (including humans). They use a historic partitioning that divides cingulate cortex in two areas called Cg1 and Cg2 that are located perpendicular to where the ACC/MCC border would be. “When we used the Cg1/Cg2 convention for our own data, the result just looked like noise,” explains Sabrina van Heukelum. The influence of cingulate cortex in controlling aggressive behavior did not get apparent because the differences in volume were thrown together and zeroed each other out.

Other researchers have previously pointed out that it would make more sense to agree on a functionally defined cross-species definition of brain areas and drop historic definitions for individual species. The work by Martha Nari Havenith and her group is the first to illustrate how dramatically this may impact scientific insight. “When it comes down to it, neuroscientists are not researching rodents to better understand mice. We want to understand the brain across species,” concludes the ESI researcher. The scientists hope their finding will bring other researchers to stop using the established but outdated rodent charting system so they have better chances to realize when they are in neuronal Asia and when they discovered America.

Original publication: van Heukeum, S., Mars, R.B., Guthgrie, M., Buitelaar, J.K., Beckmann, C.F., Tiesinga, P.H.E., Vogt, B.A., Glennon, J.C., Havenith, M.N. (2020). Where is cingulate cortex? A cross-species view. TINS 43(5), P285-299. https://doi.org/10.1016/j.tins.2020.03.007

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#Sciart!😊Two @maxplanckpress researchers, Hermann Cuntz & Marvin Weigand, will showcase their work on computer-generated #neurons at the Centre #Pompidou in #Paris @ the exhibition "Neurons | Simulated intelligence" from 26 Feb - 20 Apr 2020 https://t.co/2Isg8Wk3dQ pic.twitter.com/zEbAbddrJg

— Max Planck Society (@maxplanckpress) February 26, 2020

Hermann, exhibiting at a world famous art museum as an artist is exeptional as a researcher even more so. How did this come about?

Hermann Cuntz: It was a whole chain of events that led us to contribute to this exhibition at the Centre Pompidou. It actually started when my PostDoc boss Michael Häuser submitted one of the pictures of these artificial nerve cells for the Wellcome Image Awards competition. The theme was “most beautiful scientific picture of the year” or something along those lines. We actually won the prize and the picture was exhibited at the Wellcome Collection in London. This but also others of our pictures distributed pretty well around the internet and probably that’s why science journalists starting coming up to me. One thing led to another: Someone knew someone who knew someone and one day the ZKM (Centre for Art and Media Technology) in Karlsruhe contacted me and I made an exhibit for them. It was a 360-degree film in their PanoramaLabor, and they liked it so much that they asked me to do something for a biennial the ZKM organized in 2015. Marvin had just started his doctoral thesis with me and he came up with the idea of translating the whole thing into virtual reality. That made the whole thing extra cool and apparently also made an impression on people in the art scene. In any case, the curator of the exhibition at the Centre Pompidou knew our neurons through the ZKM Biennial. And indeed, one has to say that our visualization fits the theme of the exhibition very well.

The exhibition at the Centre Pompidou is called “Neurons - simulated intelligence” and is intended to be something like a journey through the history of artificial intelligence from an artistic perspective. But there are also quite biological exhibits - a brain in formaldehyde, for example. What does your piece look like?

Marvin Weigand: Basically, we show the cortical neurons that are produced by Hermann’s model. When visitors put on the VR glasses, they get to fly through 150 of those simulated neurons. You can control the direction of flight by moving your head. Occasionally a neuron fires an action potential - then it flashes. The whole thing is accompanied by rather spherical music, which helps to shut out the real world and completes the immersive experience that one wants to achieve with Virtual Reality.

Is it a strange feeling to contribute to an art exhibition as a scientist? And do you think your work actually has artistic value?

Hermann Cuntz: I think that if we have now made it to the ZKM and the Centre Pompidou, then what we do is art. That means, the science we do is a part of contemporary art. Of course, there are artists who have nothing to do with science, but we are obviously on a border or rather a transition between disciplines. Art and science blend into each other, you can’t really distinguish between them.

Even though you are exhibiting and therefore somehow also an artist, you are actually scientists and make pictures and videos as part of your research - what scientific knowledge do you gain from your artificial neurons?

Marvin Weigand: Strictly speaking, we do not really exhibit our research. The visualization, that is these artificial neurons that look like real biological preparations, are the byproduct of what we’re actually researching. We are interested in the general rules of the architecture of the nervous system. If we think we have discovered a possible rule, such as how neurons grow their dendrites, then we put this rule into a model that predicts what a dendrite that grows according to these rules would look like. And the more realistic the artificial dendrite looks later, the better we understood the general rule behind it.

Hermann Cuntz: The pyramidal cells that we are exhibiting at the Centre Pompidou for example, come from an article I published a few years ago. In that study, I looked at dendrites not only of pyramidal cells, but from all kinds of neurons and from many different species. The paper is called “One Rule to Grow Them All” and we show that a basic rule for the growth of dendrites is to keep the cable length as short as possible and the signal transmission as fast as possible. So if you know where the cells are a dendrite has to get its inputs from, then you can calculate with our model how the optimal dendrite should look like. And the same rules can be applied over different species, over different cell types. This works in all the cases we have tried. And one of the nice things about this model is that it passes the Turing test right from the beginning. You can give these cells - the visualization of the cell - to an expert and he can no longer differentiate: Is this a real neuron or is it artificial. In fact, it once happened that a colleague gave a lecture at our institite and said in the introduction: Of course, it will never be possible to reproduce this beautiful variety of real nerve cells in a computer model. And then he showed my picture of artificially created neurons. Obviously this is a fantastic confirmation for us that we did something right. Of course, it’s not enough to count as reliable evidence, but it is an indication.

So, the visualization of the neurons is a test whether you have made correct assumptions. But the VR element is just a joke that you thought up for the artwork without any practical, scientific use for it?

Hermann Cuntz: I wouldn’t say so. Marvin’s implementation in VR allows for people who work with similar models or approaches as we do, to have the possibility to visualize the artificial cells immersively in three dimensions. And not just individual neurons, but within a network of cells. The more cells you want to look at in context, the more difficult it is to keep track. And if you can so to say experience the constellations in VR spatially, it definitely helps to gain a better understanding. Marvin may have been the first to translate neurons into VR five years ago, but there are now other groups that are doing it simply because they are coming up against the same limits of visual perception as we are.

Marvin Weigand: In fact, I would like to publish the VR implementation, not necessarily as a paper, but as a program for virtual reality glasses. Free to download for everyone. I think it could have a pretty high impact because it is still very new. And regardless of whether it is now relevant for scientific work, we could certainly reach people who have nothing to do with research and increase interest in neuroscience in general. Just now, while I was setting up the exhibition in the Centre Pompidou, a security guard approached me and said that generally speaking, he wasn’t really interested in modern art, but that he thought our piece to be very nice and he wanted to know more about it.

What’s next on your agenda, art or research?

Hermann Cuntz: Both. We’re currently talking with an Israeli artist couple about a new, interactive project. But of course most of our time and energy goes into research. One of our next projects is to study cell types not in isolation, but in a cell compound. We are now in a position to no longer let the cells grow alone in empty space, but also packed together in a piece of cortex for example. So, we are now trying to make all the cell types that we now of grow together in one simulation. And in the end, of course, we hope that we will be able to simulate electron microscopic images taken from real tissue. This will enable us to say: We expect our model to look like this - does it? If not, we still have to change something. If so, then we have already understood a lot about neural architecture.